Development and evaluation of the Measure of the International Learning Environment Status (MILES) in international higher education

The aim of this study was to develop and evaluate an instrument to assess international students' perceptions of the international learning environment called 'Measure of the International Learning Environment Status' (MILES). We based the development of the MILES on a solid theoretical framework from Moos by addressing three domains to measure the quality of the international learning environment, namely goal direction, relationships, and system change and system maintenance. We have designed and constructed the instrument in three steps. Firstly, we have collected items from relevant existing instruments and grouped them into the three domains via content analysis. Secondly, we applied a Delphi procedure involving international higher education experts from different stakeholder groups and from different cultural backgrounds to identify and reach consensus on the items comprehensively covering important elements of the international learning environment. Thirdly, we carried out an initial questionnaire evaluation. The final MILES consisted of 47 items with 13 in the first domain, 17 in the second and 17 in the third domain. The content of the domains was clearly in line with Moos theoretical framework and we interpreted the sets of items as goal direction, relationships, and supporting services, respectively. This study provides a comprehensive and systematically developed instrument for future research to better understand international students' perspectives towards the international learning environment that are supported by stakeholders from a range of cultures.</p

Student engagement and learning outcomes:an empirical study applying a four-dimensional framework

Introduction: This study applies Reeve’s four-dimensional student engagement framework to a medical education context to elucidate the relationship between behavioral, emotional, cognitive, and agentic engagement and learning outcomes. Meanwhile, we categorize learning outcomes in knowledge and skills, and added taxonomies to the cognitive education objectives for the knowledge part, including memorization, comprehension, and application. Methods: We used the China Medical Student Survey to investigate student engagement, and combined it with the Clinical Medicine Proficiency Test for Medical Schools results as a standardized measurement of learning outcomes. We performed multivariate regression analyses to delve into the effectiveness of different types of student engagement. Moreover, we evaluated the moderating roles of gender and the National College Entrance Examination (NCEE) within the relationships between student engagement and learning outcomes. Results: We observed that emotional engagement is most effective in promoting learning outcomes in basic medical knowledge and basic clinical skills. Emotional engagement and cognitive engagement could effectively contribute to learning outcomes in all three aspects of basic medical knowledge. In contrast, behavioral and agentic engagement showed negative effects on learning outcomes. Besides, we found that the results of the NCEE played a positive moderating role. Conclusion: This study provides robust evidence for the effectiveness of emotional engagement and cognitive engagement in promoting learning outcomes. Whereas behavioral and agentic engagement may not be good predictors of learning outcomes in macro-level general competence tests. We suggest a combined effort by students and institutions to promote student engagement and bridge the distance between general competency tests and daily learning activities.</p

Biological Characteristics of HLA-G and Its Role in Solid Organ Transplantation

Organ transplantation is a lifesaving option for patients with advanced diseases. Rejection is regarded as one of the most severe risk factors post-transplantation. A molecule that contributes to immune tolerance and resisting rejection is human leukocyte antigen (HLA)-G, which belongs to the non-classical major histocompatibility complex class (MHC) I family. HLA-G was originally found to play a role during pregnancy to maintain immune tolerance between mother and child. It is expressed in the placenta and detected in several body fluids as soluble factor as well as different membrane isoforms on cells. Recent findings on HLA-G show that it can also play multifaceted roles during transplantation. This review will explain the general characteristics and biological function of HLA-G and summarize the views supporting the tolerogenic and other roles of HLA-G to better understand its role in solid organ transplantation (SOT) and its complications. Finally, we will discuss potential future research on the role of HLA-G in prevention, diagnosis, and treatment in SOT

B Cell Activation and Escape of Tolerance Checkpoints:Recent Insights from Studying Autoreactive B Cells

Autoreactive B cells are key drivers of pathogenic processes in autoimmune diseases by the production of autoantibodies, secretion of cytokines, and presentation of autoantigens to T cells. However, the mechanisms that underlie the development of autoreactive B cells are not well understood. Here, we review recent studies leveraging novel techniques to identify and characterize (auto)antigen-specific B cells. The insights gained from such studies pertaining to the mechanisms involved in the escape of tolerance checkpoints and the activation of autoreactive B cells are discussed. In addition, we briefly highlight potential therapeutic strategies to target and eliminate autoreactive B cells in autoimmune diseases

Changes in T and B cell subsets in end stage renal disease patients before and after kidney transplantation

BACKGROUND: The incidence of kidney transplantation performed in elderly patients has increased steadily recently. Higher risk of infection and mortality, but lower rate of rejection, are reported in older kidney transplant patients. This study aims to analyze the effect of transplantation on aging of T and B cells in kidney transplant patients, with the emphasis on age and Cytomegalovirus (CMV) latency. RESULTS: We included 36 patients before and after (median 2.7 years) kidney transplantation and 27 age- and sex-matched healthy controls (HC). T and B cell subsets were measured by flow cytometry, with a focus on aged T cells (CD28-), and age associated B cells (ABCs, CD19 + CD21-CD11c+). Three years after transplantation a significant increase of total T cells among the lymphocytes was found compared to pre-transplantation and HC. Among the T cells CD4+ cells were decreased, especially naïve CD4+ cells and regulatory T cells. Total CD8+ cell proportions were increased, and proportions of naïve CD8+ cells were significantly decreased after transplantation, while CD8+ effector memory T cells re-expressing CD45RA were increased. CD28− T cells were significantly higher compared to HC after transplantation, especially in CMV seropositive patients. B cells were significantly decreased, while among B cells memory B cells and especially ABCs were increased after transplantation. CONCLUSIONS: After transplantation T and B cell subsets change towards more terminally differentiated memory cells compared to age-matched HC. Proportions of aged T cells and ABCs were associated with CMV serostatus. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-021-00254-9

E. coli-Produced BMP-2 as a Chemopreventive Strategy for Colon Cancer: A Proof-of-Concept Study

Colon cancer is a serious health problem, and novel preventive and therapeutical avenues are urgently called for. Delivery of proteins with anticancer activity through genetically modified bacteria provides an interesting, potentially specific, economic and effective approach here. Interestingly, bone morphogenetic protein 2 (BMP-2) is an important and powerful tumour suppressor in the colon and is thus an attractive candidate protein for delivery through genetically modified bacteria. It has not been shown, however, that BMP production in the bacterial context is effective on colon cancer cells. Here we demonstrate that transforming E. coli with a cDNA encoding an ileal-derived mature human BMP-2 induces effective apoptosis in an in vitro model system for colorectal cancer, whereas the maternal organism was not effective in this respect. Furthermore, these effects were sensitive to cotreatment with the BMP inhibitor Noggin. We propose that prevention and treatment of colorectal cancer using transgenic bacteria is feasible

Prophylactic vaccination with a live-attenuated herpes zoster vaccine in lung transplant candidates

BACKGROUND: Herpes zoster (HZ) is caused by the reactivation of varicella–zoster virus (VZV). Patients with lung transplants are at high risk for HZ owing to their immunocompromised status and the need for lifelong immunosuppression. In this study, patients on the waiting list for lung transplantation were vaccinated by a live-attenuated HZ vaccine (Zostavax, Merck Sharp & Dohme), and the safety and immunogenicity of this vaccine were studied. METHODS: In total, 105 patients with end-stage pulmonary disease (ESPD) were enrolled (68 participants received 1 dose of Zostavax and 37 participants were enrolled as unvaccinated controls). Among them, 43 patients underwent lung transplantation and were followed up for further analysis. VZV immunoglobulin G antibody titers and VZV-specific cell-mediated immunity (CMI) on multiple time points before and after vaccination and before and after transplantation were measured. RESULTS: Immune response to Zostavax was higher in younger patients, highest within 3 months after vaccination, and not influenced by gender or type of ESPD. Age, cytomegalovirus serostatus, and immunity to VZV at baseline impacted the subsequent immune response to the vaccine. Short-term immunosuppressant treatment had strong effects on VZV CMI levels, which returned to a high level at 6 months after transplantation in vaccinated patients. Zostavax did not impact infection or rejection rate after transplantation. CONCLUSIONS: Zostavax was safe and induced a robust humoral and cellular response for patients awaiting lung transplantation regardless of the type of ESPD. Patients younger than the recommended vaccination age of over 50 years showed a strong response and could also benefit from pre-transplant immunization

The formation of mutated IgM memory B cells in rat splenic marginal zones is an antigen dependent process

Previous studies in rodents have indicated that only a minor fraction of the immunoglobulin heavy chain variable region (IGHV-Cμ) transcripts carry somatic mutations and are considered memory B cells. This is in marked contrast to humans where nearly all marginal zone B (MZ-B) cells are mutated. Here we show in rats that the proportion of mutated IgM+ MZ-B cells varies significantly between the various IGHV genes analyzed, ranging from 27% mutated IGHV5 transcripts to 65% mutated IGHV4 transcripts. The observed data on mutated sequences in clonally-related B cells with a MZ-B cell or follicular B (FO-B) cell phenotype indicates that mutated IgM+ MZ-B and FO-B cells have a common origin. To further investigate the origin of mutated IgM+ MZ-B cells we determined whether mutations occurred in rearranged IGHV-Cμ transcripts using IGHV4 and IGHV5 genes from neonatal rat MZ-B cells and FO-B cells. We were not able to detect mutations in any of the IGHV4 and IGHV5 genes expressed by MZ-B cells or FO-B cells obtained from neonatal rat spleens. Germinal centres (GCs) are absent from neonatal rat spleen in the first few weeks of their life, and no mutations were found in any of the neonatal sequences, not even in the IGHV4 gene family which accumulates the highest number of mutated sequences (66%) in the adult rat. Therefore, these data do not support the notion that MZ-B cells in rats mutate their IGHV genes as part of their developmental program, but are consistent with the notion that mutated rat MZ-B cells require GCs for their generation. Our findings support that the splenic MZ of rats harbors a significant number of memory type IgM+ MZ-B cells with mutated IGHV genes and propose that these memory MZ-B cells are probably generated as a result of an antigen driven immune response in GCs, which still remains to be proven

Ageing of Immune System and Response to a Live-Attenuated Herpes Zoster Vaccine in Lung Transplant Candidates

The mean age of lung transplant recipients has significantly increased in recent decades. Elderly recipients have a higher risk of developing herpes zoster (HZ), and they have in general a worse response to vaccination than younger persons do. We investigated the relationship between the humoral and cellular immune response to a live-attenuated HZ vaccine (Zostavax(R), Merck Sharp and Dohme) and the frequencies of T and B cell subsets, especially aged cell subsets (CD28-T cells and age associated B cells, ABCs). In total, 37 patients awaiting lung transplantation received one dose of Zostavax(R), and peripheral blood was collected before and within 6 months after vaccination. We observed a robust immune response after vaccination. The frequencies of CD28-T cells before vaccination had no impact on the subsequent immune response to HZ vaccination. However, a higher frequency of ABCs before vaccination correlated with a lower immune response especially regarding the cellular immune response. Cytomegalovirus seropositivity was associated with increased frequencies of CD28-T cells but not with frequencies of ABCs in the patients. In conclusion, increased levels of ABCs might disturb the cellular immune response to HZ vaccination, which could lower the efficacy of such vaccination in elderly transplant recipients

The influence of mixing international and domestic students on competency learning in small groups in undergraduate medical education

BACKGROUND: Medical curricula are increasingly internationalized, with international students being mixed with domestic students in small group learning. Small group learning is known to foster competency learning in undergraduate medical education, specifically Communication, Collaboration, Leadership, and Professionalism. However, it is unclear what happens with the learning of competencies when international students are introduced in small groups. This study explores if students in international small groups master the competencies Collaboration, Leadership and Professionalism at the same level as students in domestic groups in an undergraduate medical curriculum. METHOD: In total, 1215 Students of three academic year cohorts participated in the study. They were divided into four learning communities (LCs), per year cohort, in which tutor groups were the main instructional format. The tutorials of two learning communities were taught in English, with a mix of international and Dutch students. The tutorials of the other two learning communities were taught in Dutch with almost all domestic students. Trained tutors assessed three competencies (Collaboration, Leadership, Professionalism) twice per semester, as 'Not-on-track', 'On-track', or 'Fast-on-track'. By using Chi-square tests, we compared students' competencies performance twice per semester between the four LCs in the first two undergraduate years. RESULTS: The passing rate ('On-track' plus 'Fast-on-track') for the minimum level of competencies did not differ between the mixed and domestic groups. However, students in the mixed groups received more excellent performance evaluations ('Fast-on-track') than the students in the homogenous groups of Dutch students. This higher performance was true for both international and Dutch students of the mixed groups. Prior knowledge, age, gender, and nationality did not explain this phenomenon. The effect could also not be explained by a bias of the tutors. CONCLUSION: When students are educated in mixed groups of international and Dutch students, they can obtain the same basic competency levels, no matter what mix of students is made. However, students in the mixed international groups outperformed the students in the homogenous Dutch groups in achieving excellent performance scores. Future research should explore if these findings can be explained from differences in motivation, perceived grading or social network interactions