Oil-in-water emulsion lotion providing controlled release using 2-methacryloyloxyethyl phosphorylcholine n-butyl methacrylate copolymer as emulsifier

AbstractLotion is a useful vehicle for active ingredients used to treat skin disease because it can be applied to the scalp, can cover large areas of skin, and it is easy to spread due to low viscosity. An emulsion lotion (EL) containing 2-methacryloyloxyethyl phosphorylcholine n-butyl methacrylate copolymer (PMB) as an emulsifier that provides controlled-release was developed. Diphenhydramine (DPH) was used as a model drug. Formulation with 5% DPH, 5% soybean oil, and 4% PMB in water was emulsified using a high-pressure homogenizer. Polysorbate 80 (TO) was used instead of PMB for comparison. They were applied in vitro to Yucatan micropig intact or stripped skin at a practical dose (2μL/cm2). For stripped skin, penetration of DPH from 4% PMB EL was slower than that from 1% TO EL; results for intact skin were similar. The same phenomenon was observed with application to rabbit skin in vivo. When 4% PMB EL dried on the skin, it made a thin film matrix incorporating the oil phase, which controlled the release of DPH. The release rate could be controlled by the ratio of oil phase to PMB. The EL with PMB shows promise as a vehicle for long-acting treatment of skin diseases

Training Learners to Negotiate for Meaning: An Exploratory Case Study

This paper reports on an exploratory case study investigatingthe possibility of training second language learners to beeffective interlocutors in second language learning tasks. Thestudy followed a pre-test, instruction, post-test design. Fourlearners completed a picture difference task, then receivedinstruction on negotiation for meaning, and finally completeda different version of the picture difference task. Learners alsoparticipated in stimulated recall sessions at each stage of theexperiment and completed a questionnaire at the end. Findingssuggest that learners are receptive to instruction on negotiation,that such instruction has the potential to enrich the quantityand quality of negotiation between learners, and thatinstruction on negotiation for meaning may also enhancelearners’ motivation for learning

Quality of life and physical/psychosocial factors in children and adolescents with orthostatic intolerance

Background　Orthostatic intolerance (OI), which is common in children and adolescents, negatively impacts their quality of life (QOL) due to physical symptoms that limit work, school, and daily activities. The purpose of this study is to explore the association of physical and psychosocial factors with QOL scores in children and adolescents with OI. Methods　A cross sectional observational study was conducted. The study participants included 95 Japanese pediatric patients of age 9-15 years who were diagnosed with OI from April 2010 to March 2020. The QOL scores and the QOL T-scores of children with OI assessed using the KINDL-R questionnaire at the initial visit were compared with conventional normative data. The associations of physical and psychosocial factors with the QOL T-scores were examined using multiple linear regression. Results　Pediatric patients with OI had significantly lower QOL scores than healthy children in both elementary (50.7 +/- 13.5 vs. 67.9 +/- 13.4, p Conclusions　These results suggest that the assessment of QOL, including both physical and psychosocial aspects, especially school factors, needs to be implemented earlier in children and adolescents with OI

The chimeric antibody chLpMab-7 targeting human podoplanin suppresses pulmonary metastasis via ADCC and CDC rather than via its neutralizing activity

Podoplanin (PDPN/Aggrus/T1α) binds to C-type lectin-like receptor-2 (CLEC-2) and induces platelet aggregation. PDPN is associated with malignant progression, tumor metastasis, and poor prognosis in several types of cancer. Although many anti-human PDPN (hPDPN) monoclonal antibodies (mAbs), such as D2-40 and NZ-1, have been established, these epitopes are limited to the platelet aggregation-stimulating (PLAG) domain (amino acids 29-54) of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-7, which is more sensitive than D2-40 and NZ-1, using the Cancer-specific mAb (CasMab) method. The epitope of LpMab-7 was shown to be entirely different from that of NZ-1, a neutralizing mAb against the PLAG domain according to an inhibition assay and lectin microarray analysis. In the present study, we produced a mouse-human chimeric anti-hPDPN mAb, chLpMab-7. ChLpMab-7 showed high antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Furthermore, chLpMab-7 inhibited the growth of hPDPN-expressing tumors in vivo. Although chLpMab-7 recognizes a non-PLAG domain of hPDPN, it suppressed the hematogenous metastasis of hPDPN-expressing tumors. These results indicated that chLpMab-7 suppressed tumor development and hematogenous metastasis in a neutralization-independent manner. In conclusion, hPDPN shows promise as a target in the development of a novel antibody-based therapy

Chimeric Anti-PDPN Antibody ChLpMab-2

Human podoplanin (hPDPN ), a platelet aggregation‐inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C‐type lectin‐like receptor 2 (CLEC ‐2). The overexpression of hPDPN is involved in invasion and metastasis. Anti‐hPDPN monoclonal antibodies (mAbs) such as NZ ‐1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation‐stimulating (PLAG ) domain of hPDPN . Recently, we developed a novel mouse anti‐hPDPN mAb, LpMab‐2, using the cancer‐specific mAb (CasMab) technology. In this study we developed chLpMab‐2, a human–mouse chimeric anti‐hPDPN antibody, derived from LpMab‐2. chLpMab‐2 was produced using fucosyltransferase 8‐knockout (KO ) Chinese hamster ovary (CHO )‐S cell lines. By flow cytometry, chLpMab‐2 reacted with hPDPN ‐expressing cancer cell lines including glioblastomas, mesotheliomas, and lung cancers. However, it showed low reaction with normal cell lines such as lymphatic endothelial and renal epithelial cells. Moreover, chLpMab‐2 exhibited high antibody‐dependent cellular cytotoxicity (ADCC ) against PDPN ‐expressing cells, despite its low complement‐dependent cytotoxicity. Furthermore, treatment with chLpMab‐2 abolished tumor growth in xenograft models of CHO /hPDPN , indicating that chLpMab‐2 suppressed tumor development via ADCC . In conclusion, chLpMab‐2 could be useful as a novel antibody‐based therapy against hPDPN ‐expressing tumors

The Aggregation Inhibitor Peptide QBP1 as a Therapeutic Molecule for the Polyglutamine Neurodegenerative Diseases

Misfolding and abnormal aggregation of proteins in the brain are implicated in the pathogenesis of various neurodegenerative diseases including Alzheimer's, Parkinson's, and the polyglutamine (polyQ) diseases. In the polyQ diseases, an abnormally expanded polyQ stretch triggers misfolding and aggregation of the disease-causing proteins, eventually resulting in neurodegeneration. In this paper, we introduce our therapeutic strategy against the polyQ diseases using polyQ binding peptide 1 (QBP1), a peptide that we identified by phage display screening. We showed that QBP1 specifically binds to the expanded polyQ stretch and inhibits its misfolding and aggregation, resulting in suppression of neurodegeneration in cell culture and animal models of the polyQ diseases. We further demonstrated the potential of protein transduction domains (PTDs) for in vivo delivery of QBP1. We hope that in the near future, chemical analogues of aggregation inhibitor peptides including QBP1 will be developed against protein misfolding-associated neurodegenerative diseases

Effect of ultra-high pressure on small animals, tardigrades and Artemia

This research shows that small animals, tardigrades (Milnesium tardigradum) in tun (dehydrated) state and Artemia salina cists (dried eggs) can tolerate the very high hydrostatic pressure of 7.5 GPa. It was really surprising that living organisms can survive after exposure to such a high pressure. We extended these studies to the extremely high pressure of 20 GPa by using a Kawai-type octahedral anvil press. After exposure to this pressure for 30 min, the tardigrades were soaked in pure water and investigated under a microscope. Their bodies regained metabolic state and no serious injury could be seen. But they were not alive. A few of Artemia eggs went part of the way to hatching after soaked in sea water, but they never grew any further. Comparing with the case of blue-green alga, these animals are weaker under ultra-high pressure

Intake frequency of vegetables or seafoods negatively correlates with disease activity of rheumatoid arthritis

Objective: To clarify the relationship between dietary habit and disease activity of rheumatoid arthritis (RA). Methods: This study enrolled RA patients who met the ACR/EULAR 2010 classification criteria from Kyoto University Rheumatoid Arthritis Management Alliance (KURAMA) cohort in 2015. 22-item food frequency questionnaire (FFQ) was taken for the measurement of dietary habit in a single-institution cohort of RA (Kyoto University Rheumatoid Arthritis Management Alliance: KURAMA) in 2015. The disease activities of RA using the Disease Activity Score calculated based on the erythrocyte sedimentation rate (DAS28-ESR), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire (HAQ), and serum matrix metalloproteinase-3 (MMP-3) level, the use of disease-modifying anti-rheumatic drugs (DMARDs), disease duration, rheumatoid factor, anti-cyclic citrullinated antibody, and body mass index were also examined. All of them were combined and statistically analyzed. Results: 441 RA patients (81% women; mean age 65 years; mean disease duration 15 years) were enrolled from the KURAMA cohort. Average Disease Activity Score-28 using the erythrocyte sedimentation rate (DAS28-ESR) was 2.7. Univariate analysis showed that intake frequency of vegetables had a statistically significant negative correlation with disease activity markers, such as DAS28-ESR (ρ = −0.11, p<0.01), Simplified Disease Activity Index (SDAI) (ρ = −0.16, p<0.001), matrix metalloproteinase-3 (MMP-3) (ρ = −0.21, p<0.0001), and Health Assessment Questionnaire (HAQ) (ρ = −0.13, p<0.01). Factor analysis with varimax rotation was done to simplify the relevance of disease activity to various food items. 22 foods were categorized into five dietary patterns: “seafoods”, “vegetables/fruits”, “meats/fried foods”, “snacks”, and “processed foods”. The multivariate analysis adjusted for clinically significant confounders showed that “seafoods” had statistically significant negative correlations with DAS28-ESR (β = −0.15, p<0.01), SDAI (β = −0.18, p<0.001), MMP-3 (β = −0.15, p<0.01), and HAQ (β = −0.24, p<0.0001). “Vegetables/fruits” had statistically significant negative correlations with SDAI (β = −0.11 p<0.05), MMP-3 (β = −0.12, p<0.01), and HAQ (β = −0.11, p<0.05) Conclusions: These results suggest that high intake frequency of vegetables/fruits and/or seafoods might correlate with low disease activity

A Randomized Phase 2 Trial of Antibiotic Prophylaxis Versus No Intervention for Muscle Biopsy in A Neurology Department

Muscle biopsy can be used to confirm the diagnosis of neuromuscular diseases. However, it is unclear whether antibiotic prophylaxis prior to muscle biopsy is needed to prevent surgical site infection (SSI). We are conducting a phase 2, single-center, open-labeled, prospective randomized trial to clarify the need for antibiotic prophylaxis in patients at low risk for SSI undergoing muscle biopsy. Patients will be randomized to an antibiotic prophylaxis group or a control group, and the incidence of SSI will be compared between the groups. Our findings will clarify the need for antibiotic prophylaxis in this patient population

Analysis of School Oral History : Curriculum Development and Innovation of Project-Based Learning in Japan

The purpose of this paper is to reveal the multiple processes of curriculum development and innovation of Inquiry-based learning by Japanese school teachers in secondary education. In Japan inquiry-based learning, especially Problem-based Learning and Projectbased Learning, are currently receiving considerable attention for addressing the rapid-social changes anticipoted in the knowledgebased society by the year 2030 and beyond. The curriculum based on the educational policy, the curriculum experienced by students, and the reality of the curriculum mended and experienced by teachers have not been adequatly studied. This paper presents the multiple aspects of the the curriculum development by teachers by collecting narratives from the teachers themselves as one of the research projects of the Japan Innovative Schools Network supported by OECD. The project provides a means by which both teachers and researchers can work together to develope innovative curricula