A qualitative study examining the critical differences in the experience of and response to formative feedback by undergraduate medical students in Japan and the UK.

BACKGROUND: Formative feedback plays a critical role in guiding learners to gain competence, serving as an opportunity for reflection and feedback on their learning progress and needs. Medical education in Japan has historically been dominated by a summative paradigm within assessment, as opposed to countries such as the UK where there are greater opportunities for formative feedback. How this difference affects students' interaction with feedback has not been studied. We aim to explore the difference in students' perception of feedback in Japan and the UK. METHODS: The study is designed and analysed with a constructivist grounded theory lens. Medical students in Japan and the UK were interviewed on the topic of formative assessment and feedback they received during clinical placements. We undertook purposeful sampling and concurrent data collection. Data analysis through open and axial coding with iterative discussion among research group members was conducted to develop a theoretical framework. RESULTS: Japanese students perceived feedback as a model answer provided by tutors which they should not critically question, which contrasted with the views of UK students. Japanese students viewed formative assessment as an opportunity to gauge whether they are achieving the pass mark, while UK students used the experience for reflective learning. CONCLUSIONS: The Japanese student experience of formative assessment and feedback supports the view that medical education and examination systems in Japan are focused on summative assessment, which operates alongside culturally derived social pressures including the expectation to correct mistakes. These findings provide new insights in supporting students to learn from formative feedback in both Japanese and UK contexts.

Perceived positive social interdependence in online versus face-to-face team-based learning styles of collaborative learning: a randomized, controlled, mixed-methods study.

BACKGROUND: Collaborative learning is a group learning approach in which positive social interdependence within a group is key to better learning performance and future attitudes toward team practice. Recent attempts to replace a face-to-face environment with an online one have been developed using information communication technology. However, this raises the concern that online collaborative learning (OCL) may reduce positive social interdependence. Therefore, this study aimed to compare the degree of social interdependence in OCL with face-to-face environments and clarify aspects that affect social interdependence in OCL. METHODS: We conducted a crossover study comparing online and face-to-face collaborative learning environments in a clinical reasoning class using team-based learning for medical students (n = 124) in 2021. The participants were randomly assigned to two cohorts: Cohort A began in an online environment, while Cohort B began in a face-to-face environment. At the study's midpoint, the two cohorts exchanged the environments as a washout. The participants completed surveys using the social interdependence in collaborative learning scale (SOCS) to measure their perceived positive social interdependence before and after the class. Changes in the mean SOCS scores were compared using paired t-tests. Qualitative data related to the characteristics of the online environment were obtained from the focus groups and coded using thematic analysis. RESULTS: The matched-pair tests of SOCS showed significant progression between pre- and post-program scores in the online and face-to-face groups. There were no significant differences in overall SOCS scores between the two groups. Sub-analysis by subcategory showed significant improvement in boundary (discontinuities among individuals) and means interdependence (resources, roles, and tasks) in both groups, but outcome interdependence (goals and rewards) improved significantly only in the online group. Qualitative analysis revealed four major themes affecting social interdependence in OCL: communication, task-sharing process, perception of other groups, and working facilities. CONCLUSIONS: There is a difference in the communication styles of students in face-to-face and online environments, and these various influences equalize the social interdependence in a face-to-face and online environment.

Education policies to increase rural physicians in Japan: a nationwide cohort study.

BACKGROUND: Japan has established comprehensive education-scholarship programs to supply physicians in rural areas. Their entrants now comprise 16% of all medical students, and graduates must work in rural areas for a designated number of years. These programs are now being adopted outside Japan, but their medium-term outcomes and inter-program differences are unknown. METHODS: A nationwide prospective cohort study of newly licensed physicians 2014-2018 (n = 2454) of the four major types of the programs-Jichi Medical University (Jichi); regional quota with scholarship; non-quota with scholarship (scholarship alone); and quota without scholarship (quota alone)-and all Japanese physicians in the same postgraduate year (n = 40,293) was conducted with follow-up workplace information from the Physician Census 2018, Ministry of Health, Labour and Welfare. In addition, annual cross-sectional survey for prefectural governments and medical schools 2014-2019 was conducted to obtain information on the results of National Physician License Examination and retention status for contractual workforce. RESULTS: Passing rate of the National Physician License Examination was highest in Jichi, followed in descending order by quota with scholarship, the other two programs, and all medical graduates. The retention rate for contractual rural service of Jichi graduates 5 years after graduation (n = 683; 98%) was higher than that of quota with scholarship (2868; 90%; P < 0.001) and scholarship alone (2220; 81% < 0.001). Relative risks of working in municipalities with the least population density quintile in Jichi, quota with scholarship, scholarship alone, and quota alone in postgraduate year 5 were 4.0 (95% CI 3.7-4.4; P < 0.001), 3.1 (2.6-3.7; < 0.001), 2.5 (2.1-3.0; < 0.001), and 2.5 (1.9-3.3; < 0.001) as compared with all Japanese physicians. There was no significant difference between each program and all physicians in the proportion of those who specialized in internal medicine or general practice in postgraduate years 3 to 5 CONCLUSIONS: Japan's education policies to produce rural physicians are effective but the degree of effectiveness varies among the programs. Policymakers and medical educators should plan their future rural workforce policies with reference to the effectiveness and variations of these programs.

Contextual attributes to promote positive social interdependence in problem-based learning: a focus group study.

BACKGROUND: Problem-based learning (PBL) is classified as a collaborative learning approach, wherein students learn while contributing meaning to experiences and interactions with others. An important theoretical fundament of PBL is social interdependence theory (SIT) because positive social interdependence within a group has been found to be key to better learning performance and future attitudes towards team practice. However, most previous studies in health professions education focused on cognitive outcomes, and few studies have focused on collaborative behaviors in PBL groups. The lack of this empirical insight makes implementation of PBL difficult, especially in contexts where there is limited experience with collaborative learning. Therefore, the aim of this study was to elucidate what promotes or hinders positive social interdependence and how the attributes work during PBL. METHODS: We conducted four focus groups among clinical year medical students (n = 26) who participated in PBL tutorials in the formal curriculum. We asked semi-structured questions that corresponded with the overall concept of SIT. We analyzed the transcript using constructivist grounded theory and developed a model to explain contextual attributes that promote or hinder positive social interdependence in PBL. RESULTS: Two contextual attributes of "academic inquisition" and "desire for efficiency" affect social interdependence among a student group in PBL. Academic inquisition is students' desire to engage in their academic learning, and desire for efficiency is students' attitude toward learning as an imposed duty and desire to complete it as quickly as possible. These attributes are initially mutually conflicting and constructing social interdependence through multiple steps including inquisition from a case, seeking efficient work, sharing interest in problem solving, expecting mutual contributions, and complementing learning objectives. CONCLUSION: These findings will contribute to understanding collaborative learning environments in PBL and may help explain contexts where PBL is less successful. The model can also be used as a tool to support innovation of PBL as collaborative learning.

Limited effects from professional identity formation-oriented intervention on self-regulated learning in a preclinical setting: a randomized-controlled study in Japan.

BACKGROUND: Developing self-regulated learning in preclinical settings is important for future lifelong learning. Previous studies indicate professional identity formation, i.e., formation of self-identity with internalized values and norms of professionalism, might promote self-regulated learning. We designed a professional identity formation-oriented reflection and learning plan format, then tested effectiveness on raising self-regulated learning in a preclinical year curriculum. METHODS: A randomized controlled crossover trial was conducted using 112 students at Jichi Medical University. In six one-day problem-based learning sessions in a 7-month pre-clinical year curriculum, Groups A (n = 56, female 18, mean age 21.5y ± 0.7) and B (n = 56, female 11, mean age 21.7y ± 1.0) experienced professional identity formation-oriented format: Group A had three sessions with the intervention format in the first half, B in the second half. Between-group identity stages and self-regulated learning levels were compared using professional identity essays and the Motivated Strategies for Learning Questionnaire. RESULTS: Two-level regression analyses showed no improvement in questionnaire categories but moderate improvement of professional identity stages over time (R2 = 0.069), regardless of timing of intervention. CONCLUSIONS: Professional identity moderately forms during the pre-clinical year curriculum. However, neither identity nor self-regulated learning is raised significantly by limited intervention.

Using text mining to analyze reflective essays from Japanese medical students after rural community placement.

BACKGROUND: Following community clinical placements, medical students use reflective writing to discover the story of their journey to becoming medical professionals. However, because of assessor bias analyzing these writings qualitatively to generalize learner experiences may be problematic. This study uses a process-oriented text mining approach to better understand meanings of learner experiences by connecting key concepts in extended student reflective essays. METHODS: Text mining quantitative analysis is used on self-evaluative essays (n = 47, unique word count range 43-575) by fifth-year students at a regional quota-system university in Japan that specializes in training general practitioners for underserved communities. First, six highly-occurring key words were identified: patient, systemic treatment, locale, hospital, care, and training. Then, standardized keyword frequency analysis robust to overall essay length and keyword volume used individual keywords as "nodes" to calculate per-keyword values for each essay. Finally, Principle Components Analysis and regression were used to analyze key word relationships. RESULTS: Component loadings were strongest for the keyword area, indicating most shared variance. Multiply regressing three of the remaining keywords hospital, systemic treatment, and training yielded R2 = 0.45, considered high for this exploratory study. In contrast, direct patient experience for students was difficult to generalize. CONCLUSIONS: Impressions of the practicing area environment were strongest in students, and these impressions were influenced by hospital workplace, treatment provision, and training. Text mining can extract information from larger samples of student essays in an efficient and objective manner, as well as identify patterns between learning situations to create models of the learning experience. Possible implications for community-based clinical learning may be greater understanding of student experiences for on-site precepts benefitting their roles as mentors.

Does changing from a teacher-centered to a learner-centered context promote self-regulated learning: a qualitative study in a Japanese undergraduate setting.

BACKGROUND: Previous studies indicate that a teacher-centered context could hinder undergraduates from self-regulated learning (SRL), whereas a learner-centered context could promote SRL. However, SRL development between a teacher-centered and a learner-centered context has not directly compared in undergraduate settings. Also, it is still unclear how a contextual change toward learner-centered learning could influence SRL in students, who are strongly accustomed to teacher-centered learning. METHODS: We conducted three focus groups that examined 13 Japanese medical students who left a traditional curriculum composed of didactic lectures and frequent summative tests and entered a seven-month elective course (Free Course Student Doctor or FCSD). The FCSD emphasizes student-designed individualized learning with support and formative feedback from mentors chosen by students' preference. We also conducted two focus groups that examined 7 students who remained in the teacher-centered curriculum during the same period. Students were asked to discuss their 1) motivation, 2) learning strategies, and 3) self-reflection on self-study before and during the period. Data were analyzed using thematic analysis and code comparison between the two cohorts. RESULTS: The non-FCSD participants described their motivational status as being one among a crowd set by the teacher's yardstick. Their reflection focused on minimizing the gap between themselves and the teacher-set yardstick with strategies considered monotonous and homogeneous (e.g. memorization). FCSD participants described losing the teacher-set yardstick and constructing their future self-image as an alternative yardstick. They compared gaps between their present status and future self-image by self-reflection. To fill these gaps, they actively employed learning strategies used by doctors or mentors, leading to diversification of their learning strategies. CONCLUSIONS: A contextual change toward learner-centered learning could promote SRL even in students strongly accustomed to teacher-centered learning. In the learner-centered context, students began to construct their self-image, conduct self-reflection, and seek diverse learning strategies by referring to future 'self' models.

Efficacy of an over-the-scope clip for preventing adverse events after duodenal endoscopic submucosal dissection: a prospective interventional study.

BACKGROUND: Duodenal endoscopic submucosal dissection (ESD) remains technically challenging, with a high risk of severe adverse events. Because exposure of the duodenal post-ESD mucosal defect to pancreatic juice and bile acid reportedly induces delayed perforation and bleeding, we examined whether defect closure using an over-the-scope clip (OTSC) system was useful for preventing postoperative adverse events. METHODS: From April 2016 to February 2017, a total of 50 consecutive patients with superficial non-ampullary duodenal epithelial tumors (SNADETs) larger than 10 mm, with no more than semi-circumferential spread, were prospectively enrolled in this study. All of the lesions were treated by experienced ESD operators and the post-ESD mucosal defect was closed using OTSCs. RESULTS: All of the SNADETs were completely removed by ESD, with an R0 resection rate of 88.0 %. The mean procedure and closure times were 67.3 ±â€Š58.8 minutes and 9.8 ±â€Š7.2 minutes, respectively. Although complete defect closure was achieved in 94.0 % of the patients (47/50), two patients required surgical conversion. Delayed perforation occurred in only one patient (2.1 %), who did not have successful closure of the defect, as misplacement of the OTSC exposed the muscle layer. Meanwhile, delayed bleeding occurred in three patients (6.3 %); however, the bleeding was easily controlled using endoscopic coagulation. The mean duration of postoperative hospitalization was 5.5 ±â€Š7.2 days. CONCLUSIONS: Prophylactic defect closure using OTSCs may be effective in reducing severe adverse events after duodenal ESD.

Contextual attributes promote or hinder self-regulated learning: A qualitative study contrasting rural physicians with undergraduate learners in Japan.

BACKGROUND AND OBJECTIVES: Previous studies support the notion that East Asian medical students do not possess sufficient self-regulation for postgraduate clinical training. However, some East Asian physicians who are employed in geographically isolated and educationally underserved rural settings can self-regulate their study during the early phase of their postgraduate career. To explore the contextual attributes that contribute to self-regulated learning (SRL), we examined the differences in self-regulation between learning as an undergraduate and in a rural context in East Asia. METHODS: We conducted interviews and diary data collection among rural physicians (n = 10) and undergraduates (n = 11) in Japan who undertook self-study of unfamiliar diseases. We analyzed three domains of Zimmerman's definition of SRL: learning behaviors, motivation, and metacognition using constructivist grounded theory. RESULTS: Rural physicians recognized their identity as unique, and as professionals with a central role of handling diseases in the local community by conducting self-study. They simultaneously found themselves being at risk of providing inappropriate aid if their self-study was insufficient. They developed strategic learning strategies to cope with this high-stakes task. Undergraduates had a fear of being left behind and preferred to remain as one of the crowd with students in the same school year. Accordingly, they copied the methods of other students for self-study and used monotonous and homogeneous strategies. CONCLUSIONS: Different learning contexts do not keep East Asian learners from being self-regulated. Awareness of their unique identity leads them to view learning tasks as high-stakes, and to initiate learning strategies in a self-regulated manner. Teacher-centered education systems cause students to identify themselves as one of the crowd, and tasks as low-stakes, and to accordingly employ non-self-regulated strategies.

The effect and possible clinical efficacy of in vivo inhibition of neutrophil extracellular traps by blockade of PI3K-gamma on the pathogenesis of microscopic polyangiitis.

OBJECTIVE: Neutrophil extracellular traps (NETs) are peculiar structures composed of the externalized chromatin with intracellular proteins and formed by activated neutrophils in a reactive oxygen species (ROS)-dependent manner. Aberrant NETs are considered to be autoantigens for anti-neutrophil cytoplasmic antibodies (ANCAs) underling the development of microscopic polyangiitis (MPA). However, little is known regarding the therapeutic efficacy of in vivo inhibition of NET formation (NETosis) on MPA pathogenesis. This study determines whether reducing NETosis prevents ANCA production and improves characteristic involvement. METHODS: A mouse model of MPA induced by administering a novel extract from Candida albicans was devised. By applying this method to mice lacking phosphoinositide 3-kinase gamma (PI3K-gamma), which is indispensable for ROS production in neutrophils, we investigated the levels of in vivo NETs, ANCA titers and histological damage. RESULTS: Our model exhibited accumulation of NETs in vivo, elevation of ANCA titers and characteristic pathologies mimicking human MPA, including small-vessel vasculitis and crescentic glomerulonephritis. Strikingly, these abnormalities were reduced by genetically and/or pharmacologically blocking PI3K-gamma. Moreover, a pharmacological PI3K-gamma blockade decreased the levels of human NETs. CONCLUSION: Our results suggest that in vivo inhibition of NETosis by blocking PI3K-gamma could be a promising therapeutic strategy for the pathogenesis of MPA.

Long-term clinical outcomes of endoscopic submucosal dissection for colorectal neoplasms in 423 cases: a retrospective study.

Background and study aim Endoscopic submucosal dissection (ESD) is known as a curative treatment for colorectal superficial neoplasms. There is however a need for more long-term clinical data to establish the full advantages of colorectal ESD regarding very low recurrence rates. The aim of this retrospective study was to determine long-term clinical outcomes of colorectal ESD. Methods A total of 423 lesions treated by ESD for colorectal adenoma/dysplasia or adenocarcinoma between 1998 and 2008 at a single high volume referral center were included. We conducted a retrospective survey on patients with follow-up and obtained complete 1-, 3-, and 5-year outcome data for 358 (85 %), 292 (69 %), and 209 (49 %) lesions, respectively. Curative resection was defined when the pathological specimen had carcinoma-free resection margins, irrespective of piecemeal or en bloc resection, without submucosal deep invasion (≥ 1000 µm), lymphovascular involvement, or a poorly differentiated adenocarcinoma component. Results After a median 4.9 years of follow-up, the 3-year overall cumulative endoscopic recurrence rate and cancerous recurrence rate were 2.9 % (95 % confidence interval [95 %CI] 1.2 - 4.7) and 1.1 % (0 - 2.1), respectively. The 5-year overall cumulative endoscopic recurrence and cancerous recurrence rates were 3.8 % (1.7 - 5.9) and 1.6 % (0.1 - 3.0), respectively. In 361 lesions eligible for endoscopic follow-up, the 3-year endoscopic recurrence and cancerous recurrence rates were 2.4 % (0.8 - 4.1) and 0.4 % (0 - 1.4), respectively. Multivariate analysis revealed that piecemeal resection and submucosal deep tumor invasion were associated with recurrence. Conclusions The current study demonstrated favorable long-term clinical outcomes of colorectal ESD when en bloc curative resection is achieved.

Photoelectron Spectroscopy and Ab Initio Calculations of CS3(-) Isomers: Carbon Trisulfide and Carbon Disulfide S-Sulfide Anions.

Carbon sulfides are known as a class of binary compounds that can exist in various isomeric and/or polymeric forms. As for a sulfur-rich compound with the composition formula CS3, two possible constitutional isomers have been proposed experimentally or theoretically for the neutral species and its corresponding radical cation and anion. Although the previous studies claim that one isomer has a carbon trisulfide (CS3) C-centered configuration and the other has a carbon disulfide S-sulfide (SCSS) chain configuration, they have not yet been fully identified by a spectroscopic method. In this study, we have prepared the anions of those isomers in the gas phase by employing two types of reactions: dissociative electron attachment to 1,3-dithiole-2-thione for CS3(-) formation and the S(-) + CS2 ion-molecule reaction for SCSS(-). Photoelectron spectroscopic measurements reveal that the reactions result in the production of two anionic species that can be well distinguished by their vertical detachment energy. With the aid of ab initio calculations, they are identified distinctively as the anions of carbon trisulfide and carbon disulfide S-sulfide.

A first report of East Asian students' perception of progress testing: a focus group study.

BACKGROUND: Progress testing (PT) is used in Western countries to evaluate students' level of functional knowledge, and to enhance meaning-oriented and self-directed learning. However, the use of PT has not been investigated in East Asia, where reproduction-oriented and teacher-centered learning styles prevail. Here, we explored the applicability of PT by focusing on student perceptions. METHODS: Twenty-four students from Years 2, 3, and 5 at Jichi Medical University in Japan attended a pilot PT session preceded by a brief introduction of its concept and procedures. Variations in obtained test scores were analyzed by year, and student perceptions of PT were explored using focus groups. RESULTS: Formula scores (mean ± standard deviation) in Years 2, 3, and 5 were 12.63 ± 3.53, 35.88 ± 14.53, and 71.00 ± 18.31, respectively. Qualitative descriptive analysis of focus group data showed that students disfavored testing of medical knowledge without tangible goals, but instead favored repetitive assessment of knowledge that had been learned and was tested on a unit basis in the past in order to achieve deep learning. Further, students of all school years considered that post-test explanatory lectures by teachers were necessary. CONCLUSIONS: East Asian students' perceptions indicated that, in addition to their intensive memorization within narrow test domains compartmentalized by end-of-unit tests, the concept of PT was suitable for repetitive memorization, as it helped them to integrate their knowledge and to increase their understanding. Post-test explanatory lectures might lessen their dislike of the intangible goals of PT, but at the expense of delaying the development of self-directed learning. Key issues for the optimization of PT in East Asia may include administration of PT after completed end-of-unit tests and a gradual change in feedback methodology over school years from test-oriented post-test lectures to the provision of literature references only, as a means of enhancing test self-review and self-directed learning.

Development of a new classification for in vivo diagnosis of duodenal epithelial tumors with confocal laser endomicroscopy: A pilot study.

BACKGROUND AND AIM: Confocal laser endomicroscopy (CLE) has been established for in vivo diagnosis of various gastrointestinal diseases. However, validated criteria for confocal diagnosis of duodenal tumors do not exist. Therefore, the aim of the present pilot study was to develop a novel classification for in vivo optical diagnosis of duodenal tumors using CLE. METHODS: Consecutive patients with duodenal tumorous lesions were included. First, an initial classification system was developed which was then validated. Histopathology was used as a reference standard. RESULTS: A simple classification system for in vivo diagnosis of duodenal epithelial tumors using CLE was developed. Sensitivity, specificity, and accuracy were 90%, 100%, and 97%, respectively. Positive and negative predictive values were calculated as 100% and 96%. The kappa coefficient representing consistency was 1 between observers and within each observer. CONCLUSION: A new classification for in vivo diagnosis of duodenal epithelial tumors using confocal imaging has been developed. The new classification system allows adequate prediction of histology and could therefore be used to guide subsequent therapy of duodenal lesions.

Successful re-administration of imatinib without recurrence of tumor lysis syndrome in a patient with peritoneal gastrointestinal stromal tumor.

A 69-year-old man with disseminated peritoneal gastrointestinal stromal tumor (GIST) developed tumor lysis syndrome (TLS) during imatinib therapy. Although the TLS improved after imatinib therapy was discontinued, the tumor growth accelerated. Therefore, imatinib therapy was restarted at a reduced dose, and a TLS prevention strategy was implemented that involved aggressive hydration and therapy with rasburicase and allopurinol. The tumor almost completely diminished without recurrence of TLS, and the patient has been in remission for 26 months. In the 2 previously reported cases of GIST with TLS, none of the patients survived. Our case report suggests that a TLS prevention strategy could be effective when restarting imatinib chemotherapy in sensitive solid tumors like GISTs.

Adapting the Motivated Strategies for Learning Questionnaire to the Japanese Problem-Based Learning Context: A Validation Study.

The COVID-19 pandemic has greatly changed medical education, and medical trainees' self-regulation has become more emphasized. In Japan, the concept of self-regulated learning has not been fully applied in health profession education due to a lack of effective measurement tools. We aimed to validate the translated Japanese version of the Motivated Strategies for Learning Questionnaire in the context of Problem-Based Learning (J-MSLQ-PBL). The questionnaire employs a seven-point Likert-type scale with 81 items and is categorized into two sections: motivation and learning strategies. An exploratory factor analysis (EFA) was conducted by using Promax rotation to examine the factor structure of the scale, using the collected data from 112 Japanese medical students. Factor extraction was based on a scree plot investigation, and an item was accepted when the factor loading was ≥0.40. In the motivation section, the extracted factors from the EFA were well aligned with the subscales of the original MSLQ, including "Self-Efficacy for Learning and Performance", "Task Value", "Self-Efficacy for Learning and Performance", "Test Anxiety", "Extrinsic Goal Orientation", and "Intrinsic Goal Orientation". In the learning strategies, the extracted factors poorly matched the structure of the original subscales. This discrepancy could be explained by insufficient translation, the limited sample size from a single medical school, or cross-cultural differences in learning strategies between Western and Japanese medical students. Only the motivation part of the J-MSLQ-PBL should be implemented to measure the competency elements of self-regulated learning in Japan.

The levels of soluble ST2 in sera and bullous fluid from patients with bullous pemphigoid.

Soluble ST2 (sST2) is a soluble form of the transmembrane receptor for interleukin (IL)-33, ST2L, and is a member of the IL-1 receptor family. sST2 antagonizes IL-33-ST2L signaling by competing with ST2L as a decoy receptor for IL-33. We investigated the sST2 and IL-33 levels in the sera and bullous fluid of bullous pemphigoid patients and compared these with the corresponding levels in normal healthy controls. As controls, we used the bullous fluid of burn patients and that from suction blisters induced in normal healthy volunteers. The serum sST2 concentrations of bullous pemphigoid patients were higher than those of healthy controls. Serum sST2 levels correlated with the area of skin involvement and serum lactate dehydrogenase levels, suggesting that serum sST2 levels reflect disease severity. The sST2 concentrations in bullous fluid from bullous pemphigoid patients were higher than those from controls. The concentration of IL-33 ligand was below the detectable limits in all enzyme-linked immunosorbent assay samples. Thus, our study suggested that the serum sST2 level may be a useful marker of disease severity and that sST2 functions as a negative regulator in the pathophysiology of bullous pemphigoid.

Sustained elevation of interleukin-33 in sera and synovial fluids from patients with rheumatoid arthritis non-responsive to anti-tumor necrosis factor: possible association with persistent IL-1ß signaling and a poor clinical response.

Although TNF inhibitors have dramatically improved the outcome of patients with rheumatoid arthritis, 30-40% of patients do not respond well to them and treatment needs to be changed. In an effort to discriminate good and poor responders, we focused on the change in serum and synovial fluid levels of interleukin (IL-) 33 before and after treatment with TNF inhibitors. They were also measured in synovial fluids from 17 TNF inhibitor-naïve patients, and fibroblast-like synoviocytes (FLS) in-culture from 6 patients and correlated with various pro-inflammatory cytokines. Serum levels of IL-33 at 6 months after treatment decreased significantly in responders, while they did not change in non-responders. Synovial fluid levels of IL-33 in 6 patients under treatment with TNF inhibitors stayed high in 3 who were refractory and slightly elevated in 2 moderate responders, while they were undetectable in one patient under remission. Among inflammatory cytokines measured in 17 synovial fluids from TNF inhibitor-naïve patients, levels of IL-33 showed a significant positive correlation only to those of IL-1ß. IL-1ß increased IL-33 expression markedly in FLS in vitro, compared to TNF-α. IL-1ß might be inducing RA inflammation through producing pro-inflammatory IL-33 in TNF inhibitor-hypo-responders. Sustained elevation of serum and/or synovial levels of IL-33 may account for a poor response to TNF inhibitors, although how TNF inhibitors affect the level of IL-33 remains to be elucidated.

Long-term clinical clerkship improves medical students' attitudes toward team collaboration.

Objectives: To examine the related factors associated with medical students' attitudes toward team collaboration. Methods: This cross-sectional study targeted medical students, residents, and doctors. A survey was conducted from 2016 to 2017 using the Japanese version of the Jefferson Scale of Attitudes Toward Interprofessional Collaboration (JeffSATIC-J), which evaluated "working relationship" and "accountability." We analyzed 2409 questionnaire responses with JeffSATIC-J items and the gender item. Analysis of variance was used for factors associated with the JeffSATIC-J score and Spearman's rank correlation coefficient for the relationship between educational intervention and the JeffSATIC-J score. Results: First-year students' scores were the highest (F(2, 2045) = 13.42 to 18.87, p < .001), and female students' scores were significantly higher than those of male students (F(1, 2045) = 21.16 to 31.10, p < .001). For residents' scores, the institution was not a significant variable. Female "accountability" scores were significantly higher than those of males (F (1,108) = 4.95, p = .03). Gender was not a significant variable for doctors' scores. Sixth-year students' scores were significantly correlated with the length of clinical clerkship (r(5)=.78 to .96, p<.05), with the exception of females' "working relationship" scores. The medical school with the highest JeffSATIC-J scores had the longest clinical clerkship in the community. Conclusions: These results indicate that long-term clinical clerkship in the community at higher grades is important in improving medical students' attitudes toward team collaboration. A qualitative study is required to confirm our findings.

Characterization of ST2 transgenic mice with resistance to IL-33.

IL-33, a member of the IL-1 family, activates MAPK and NF-kappaB through its receptor ST2L and IL-1RAcP. ST2, a member of the IL-1R superfamily, is a secreted form of ST2 gene products, which has been shown to act as a decoy receptor for IL-33 and to inhibit the IL-33/ST2L/IL-1RAcP signaling pathway. In this work, we generated ST2 transgenic mice. In control mice, intraperitoneal administration of IL-33 caused an increased number of eosinophils in blood and in peritoneal cavity, an increased number of peritoneal M Phi, splenomegaly, accumulation of periodic acid-Schiff-positive material in the lung, and high concentrations of serum IL-5 and IL-13. However, these alterations were hardly detectable in ST2 Tg mice. In peritoneal M Phi from IL-33-stimulated mice, mRNA expression of M2 M Phi marker genes were increased compared with thioglycollate-elicited peritoneal M Phi. The IL-33-stimulation also increased the secretion of IL-6 from M Phi. However, when the IL-33 was preincubated with ST2 prior to its addition to the M Phi cultures, the secretion of IL-6 was attenuated. These data suggest that, though IL-33 induced the Th2-type immune responses and infiltration of M2 type M Phi into the peritoneal cavity, ST2 can downregulate these reactions both in vivo and in vitro.