Encouraging medical students to become surgeons? Impact of psychological and surgical factors on career choice at medical school.

Aim: Training decisions are viewed as a problem by the majority of medical students.In the present study we compared sociodemographic and psychological characteristics of students who are interested in surgical training to those who preferred a non-surgical specialty. Furthermore, we examined whether students who wish to be trained as surgeons performed better than their non-surgical counterparts in a course designed to acquire skills in minimally invasive surgery. Method: From October 2020 to January 2021 we performed a cross-sectional survey among 116 medical students prior to their year of practical training at Christian-Albrechts University in Kiel. Based on their intended field of specialization, the students were divided into a non-surgical and a surgical group. Sociodemographic and psychological characteristics such as self-efficacy expectations, resilience and stress perception were evaluated and compared between groups. Simultaneously, we compared their surgical performance in two laparoscopic exercises and their self-assessment as surgeons. Statistical differences between the training groups were determined by the Mann-Whitney U test or Pearson's Chi square test. Results: Ninety-two students participated in the study, of whom 64.1% intended to train in a non-surgical specialty and 35.9% in a surgical specialty. Students who wished to be trained as surgeons had higher general self-efficacy expectations (p<0.001) and greater resilience (p=0.009). However, on comparison they had a lower stress level (p=0.047). The inter-group comparison of training results and self-assessment as surgeons revealed no unequivocal differences in surgical performance. Conclusion: Interest in surgical specialties is correlated, among other factors, with the strength of psychological skills such as general self-efficacy expectations, resilience and stress perception. Early attention to these psychological resources in academic training might assist medical students in future career choices.

Genomic deletion of Bcl6 differentially affects conventional dendritic cell subsets and compromises Tfh/Tfr/Th17 cell responses.

Conventional dendritic cells (cDC) play key roles in immune induction, but what drives their heterogeneity and functional specialization is still ill-defined. Here we show that cDC-specific deletion of the transcriptional repressor Bcl6 in mice alters the phenotype and transcriptome of cDC1 and cDC2, while their lineage identity is preserved. Bcl6-deficient cDC1 are diminished in the periphery but maintain their ability to cross-present antigen to CD8+ T cells, confirming general maintenance of this subset. Surprisingly, the absence of Bcl6 in cDC causes a complete loss of Notch2-dependent cDC2 in the spleen and intestinal lamina propria. DC-targeted Bcl6-deficient mice induced fewer T follicular helper cells despite a profound impact on T follicular regulatory cells in response to immunization and mounted diminished Th17 immunity to Citrobacter rodentium in the colon. Our findings establish Bcl6 as an essential transcription factor for subsets of cDC and add to our understanding of the transcriptional landscape underlying cDC heterogeneity.

German first-year medical students' expectations of their professional life - concerns and hopes: A project report.

Aim: Expectations among medical students towards their future professional life are affected by intrinsic and extrinsic factors which may change during years of medical school. The aim of this study is to gain further insight into students' expectations of their professional life at the beginning of medical school. Findings regarding contextual influences can be used to improve curricula and student guidance. Methods: The project report based on an online survey among three cohorts of first year medical students at the LMU. The questionnaire consisted of six open-ended questions which addressed the student's motivation, expectations, anticipations and concerns of their professional life. Questions were also asked about presumed personal development and influence on private life. An inductive coding was used in this qualitative content analysis. Results: Written responses from 591 participants were coded, categorized and summarized into four main themes: personal life, work, science, personal issue. Despite coming from different cohorts, the occurrence of the main themes showed the same trend in all student groups. Students are worried most about the work-life-balance, and they expect it to be a difficult issue. But many of our first-year students are optimistic that they will be able to establish a good work-life-balance or that the working conditions will have changed to a manageable workload at the time they will enter their first jobs. The majority of our students expect to become more self-confident with enhanced empathy and team-working ability and more patient and stress-resistant in daily challenges. Conclusion: The medical students emphasize the gender-neutral desire for work-life balance. So, they expect improved working conditions for the future - an ongoing challenge for the health care system.

Principles of oncology taught in a one-week course.

BACKGROUND: Growing challenges in oncology require evolving educational methods and content. International efforts to reform oncology education are underway. Hands-on, interdisciplinary, and compact course formats have shown great effectiveness in the education of medical students. Our aim was to establish a new interdisciplinary one-week course on the principles of oncology using state-of-the-art teaching methods. METHODS: In an initial survey, medical students of LMU Munich were questioned about their current level of knowledge on the principles of oncology. In a second two-stage survey, the increase in knowledge resulting from our recently established interdisciplinary one-week course was determined. RESULTS: The medical students' knowledge of clinically important oncological topics, such as the diagnostic workup and interdisciplinary treatment options, showed a need for improvement. Knowledge of the major oncological entities was also in an expandable state. By attending the one-week course on the principles of oncology, students improved their expertise in all areas of the clinical workup in oncology and had the opportunity to close previous knowledge gaps. In addition, students were able to gain more in-depth clinical knowledge on the most common oncological entities. CONCLUSION: The interdisciplinary one-week course on the principles of oncology proved to be an effective teaching method to expand the knowledge of the future physicians to an appropriate level. With its innovative and interdisciplinary approach, the one-week course could be used as a showcase project for the ongoing development of medical education in Germany.

Online medical history taking course: Opportunities and limitations in comparison to traditional bedside teaching.

Objective: Obtaining a systematic medical history (MH) from a patient is a core competency in medical education and plays a vital role in the diagnosis of diseases. At the Faculty of Medicine at LMU Munich, students have their first course in MH taking during their second year. Due to the COVID-19 pandemic, the traditional bedside MH taking course had to be transformed into an online course (OC). Our objectives were to implement an online MH taking course, to evaluate its feasibility and to compare the evaluation results to a historic cohort that had undertaken the traditional bedside teaching course (BTC). Methods: 874 second-year students participated in the OC (BTC=827). After teaching the theoretical background via asynchronous online lectures, students participated in a practical exercise with fellow students using the video communication platform Zoom where they were able to practice taking a MH on the basis of fictitious, text-based patient cases. Students were then asked to evaluate the course through a standardized online survey with 31 questions on teaching quality and self-perceived learning success, which had also been used in previous years. The survey results were compared to the results of the historic cohort using the Mann-Whitney U test. Results: A total of n=162 students (18.5%) evaluated the OC. In the historic cohort, n=252 (30.5%) completed the survey. 85.3% of the OC respondents thought that the atmosphere during the practical exercise was productive and 83.0% greatly appreciated the flexibility in terms of time management. Moreover, they appreciated the online resources as well as having the opportunity to undertake a MH taking course during the COVID-19 pandemic. 27.7% of the respondents thought that traditional BTCs should be supplemented through more online activities in the future. With respect to the ability of independently taking a MH upon completion of the course, the OC was rated significantly lower relative to the BTC (mean OC=2.4, SD=±1.1 vs. mean BTC=1.9, SD=±1.1 (1=strongly agree; 5=strongly disagree); p<0.0001). Conclusion: OCs are a feasible format and seem to convey the theory and practical implementation in a peer-exercise format of MH taking to medical students. The theoretical background can be acquired with great flexibility. Nevertheless, the students' self-appraisal suggested that the traditional teaching format was more effective at teaching MH taking skills. Thus, we propose a blended learning concept, combining elements of both formats. In this context, we suggest prospective, randomized trials to evaluate blended learning approaches.

One academic year under COVID-19 conditions: two multicenter cross-sectional evaluation studies among medical students in Bavarian medical schools, Germany students' needs, difficulties, and concerns about digital teaching and learning.

BACKGROUND: Since March 2020, COVID-19 has created a need for adaptation in many areas of life. This study explores medical students' perspectives on digital teaching under conditions of the COVID-19 pandemic. It focuses on expectations and concerns about digital teaching, the evaluation of specific aspects of teaching, and requests for future teaching. METHODS: Six German faculties have joined forces within the Bavarian network for medical education to develop and deploy a common core questionnaire. Cross-sectional surveys were conducted at the end of the summer semester 2020 and winter semester 2020/21. Medical students from different semesters participated in the online survey. Data was analyzed descriptively and/or inferentially. Item differences across semesters were examined using contingency tables and Chi2 tests. Mean values were compared using the independent samples t-test; answer frequencies in retrospective and prospective concerns were compared using contingency tables and Chi2 tests with Yates' correction. RESULTS: In the summer semester 2020, 1565 students and in winter semester 2020/21, 1727 students took part in the survey. Students' main prospective concern was lack of social exchange between fellow students (70%), but also with teachers. Second and third most often concerns were a lack of practical training (68%) and lack of integration of on-site digital teaching (50%). Approximately 7% of the students lacked sufficient access to technical equipment.. Approximately 39% of the students lacked a sufficient internet connection for synchronous digital teaching, 17% for asynchronous digital teaching. On-site teaching was the preferred form of teaching (60%), and there was a preference for asynchronous (24%) over synchronous (15%) digital teaching. Teaching recordings (79%) were particularly popular to complement future on-site teaching. CONCLUSIONS: The following areas of education under COVID-19 conditions are highly important to medical students: adequacy of information sharing, integration of opportunities for exchange with fellow students and teachers, possibility to perform practical trainings. After the normalization of the pandemic situation, on-site teaching should be supplemented with blended learning concepts such as the inverted classroom model. Percentages of results are rounded averages from summer and winter semesters.

Misjudgment of Skills in Clinical Examination Increases in Medical Students Due to a Shift to Exclusively Online Studies during the COVID-19 Pandemic.

In medical school, practical capacity building is a central goal. During the COVID-19 pandemic, a shift to online teaching methods in university was mandated in many countries to reduce risk of SARS-CoV-2 transmission. This severely affected the teaching of psychomotor ability skills such as head and neck examination skills, resulting in a share of students that have only been taught such ENT-specific examination skills with online courses; our study aimed to measure performance and capacity of self-evaluation in these students. After completing a new extensive online Ear Nose Throat (ENT) examination course, we conducted a standardized clinical skills exam for nine different ENT examination items with 31 students. Using Likert scales, self-evaluation was based on questionnaires right before the clinical skills exam and objective evaluation during the exam was assessed following a standardized regime. Self-evaluation and objective evaluation were correlated. To compare the exclusive online teaching to traditional hands-on training, a historic cohort with 91 students was used. Objective examination performance after in-classroom or online teaching varied for single examination items while overall assessment remained comparable. Overall, self-evaluation did not differ significantly after online-only and in-classroom ENT skill teaching. Nevertheless, misjudgment of one's skill level increased after online-only training compared to in-classroom teaching. Highest levels of overestimation were observed after online training in simple tasks. While gender and interest in ENT did not influence self-evaluation and misjudgment, higher age of participants was associated with an overestimation of skills. Medical students with online-only training during the COVID-19 pandemic achieved similar ENT examination skills to those with traditional on-campus training before the pandemic. Nevertheless, students with online-only training were more prone to misjudge their skills when they assessed their skills. Due to the COVID-19 pandemic, current medical students and graduates might therefore lack individual specific psychomotor skills such as the ENT examination, underlining the importance of presence-based teaching.

Quality assurance and curricular development of medical faculties using graduate surveys: Challenges - proposal of a core questionnaire - implementation guide.

Graduate surveys provide valuable information to further improve and develop an academic study program. The aim of this project report is to point out the relevance of these surveys for medical schools and to offer guidance on planning and implementing such surveys so that comparable evaluations of medical degree programs are possible. The authors of this project report were asked by the MFT working subgroup on Quality Assurance in Education to generate quality recommendations for surveying medical graduates. To accomplish this, the questionnaires used by the medical schools to survey graduates were closely inspected and analyzed. A questionnaire containing core and optional questions was created as part of this project. A comprehensive matrix was also developed listing all of the procedural elements of graduate surveys.

Emotional and Psychological Effects of Dysphagia: Validation of the Jugendwerk Dysphagia Emotion and Family Assessment (JDEFA).

INTRODUCTION: Patients suffering from swallowing disorders are experiencing emotional effects like anger, anxiety, and sadness. This may be affecting patient-therapist relation and family functioning. To assess emotional reaction and their influence on family systems, we developed a 55-item questionnaire based on the Atlas of Emotion and the Calgary Family Intervention Model. METHODS: We recruited more than 160 participants to validate an online survey, namely the Jugendwerk Dysphagia Emotion and Family Assessment Score (JDEFA). Forty-Nine health care workers, patients, and family members completed the survey and provided additional comments regarding interactions of emotions and dysphagia. Analysis was accomplished by non-parametric tests and principal component analyses with Varimax rotation. Additionally, we accomplished a qualitative content analysis taking a phenomenological single-coder approach. RESULTS: Analysis revealed a Cronbach's Alpha of 0.93. Using primary component analyses, justified by a Kaiser-Meyer-Olkin value of 0.81, we identified two main factors (emotion and family). Patients experienced sadness and anger more often than health care providers, whereas family members felt anxiety even more often. Our qualitative analysis revealed 20 themes (7 for anger, 2 enjoyment, 4 sadness, 3 anxiety, 2 disgust, 1 shame, and 1 punishment). Predominantly, the fear of choking was mentioned by patients, whereas professionals reported about the fear of making mistakes. CONCLUSION: The JDEFA is a valid and reliable testing tool for the assessment of swallowing disorders concerning emotional aspects and family functioning. Both factors have a significant role in dysphagia and evaluations should go along with functional assessments and psychological scores for a holistic understanding of swallowing disorders.

[ToSkORL: self- and objective assessment of examination skills in the head and neck region]. / ToSkORL: Selbst- und Fremdeinschätzung bei der Untersuchung des Kopf-Hals-Bereichs.

BACKGROUND: A central goal of medical school is acquisition of theoretical and practical competences. However, evidence on how capacity acquisition can be measured for special examination techniques is scarce. ToSkORL (Teaching of Skills in Otorhinolaryngology) is a project aimed at scientifically and didactically investigating students' self-evaluation skills in otorhinolaryngologic and head and neck examination techniques. METHODS: During the examination techniques course, a standardized oral and practical exam for nine different techniques was conducted. Using Likert scales, self-evaluation was based on questionnaires before the clinical skills exam and objective evaluation was performed by the examiners during the examination using a checklist. Self- and objective evaluation were correlated. Nine different examination skills were assessed 42 times each by a total of 91 students. RESULTS: Self-evaluation of competence in the different examination skills varied widely. Nevertheless, self- and objective evaluation correlated well overall, independent of age and gender. Students highly interested in otorhinolaryngology rated their own skills higher but tended toward overestimation. For examination items with intermediate difficulty, the highest divergences between self- and objective evaluation were found. CONCLUSION: Student self-evaluations are an appropriate instrument for measuring competences in otorhinolaryngologic examinations. Instructors should focus on items with allegedly intermediate difficulty, which are most often over- and underestimated.

Medical students' engagement in the context of the SARS-CoV-2 pandemic: The influence of psychological factors on readiness to volunteer.

Objective: To avert staff shortages during the first wave of the SARS-CoV-2 pandemic in spring 2020, the medical faculties of the Technical University of Munich (TUM) and the Ludwig Maximilian University of Munich (LMU) appealed to their students to volunteer for relief work. In this study, we examine the influence of psychological factors on the students' decisions to respond to this call or not. Methodology: We report on a cross-sectional study based on an online survey among medical students at the TUM and LMU. The survey consisted of a questionnaire containing items on motivation and other factors related to the decision for or against volunteering. Questions were also asked about anxieties regarding COVID-19 and the occurrence of depressive symptoms, as well as about resilience. Results: Responses from 244 participants were analysed. Students' decisions to volunteer revealed both altruistic and introjected motivations. For those students who did not volunteer, time overlaps and workload related to other activities played an important role. Between the two groups, no significant difference was detected in terms of their resilience and COVID-19-related anxieties. However, the non-volunteering students reported a significantly higher prevalence of depressive symptoms. Conclusion: Sense of duty and the desire to help were, according to the students, the most important reasons for volunteering. Depressive symptoms and lack of time made volunteering less likely. Resilience and COVID-19-related anxieties do not seem to have had any influence on the decision to volunteer or not.

Impaired function and delayed regeneration of dendritic cells in COVID-19.

Disease manifestations in COVID-19 range from mild to severe illness associated with a dysregulated innate immune response. Alterations in function and regeneration of dendritic cells (DCs) and monocytes may contribute to immunopathology and influence adaptive immune responses in COVID-19 patients. We analyzed circulating DC and monocyte subsets in 65 hospitalized COVID-19 patients with mild/moderate or severe disease from acute illness to recovery and in healthy controls. Persisting reduction of all DC subpopulations was accompanied by an expansion of proliferating Lineage-HLADR+ cells lacking DC markers. Increased frequency of CD163+ CD14+ cells within the recently discovered DC3 subpopulation in patients with more severe disease was associated with systemic inflammation, activated T follicular helper cells, and antibody-secreting cells. Persistent downregulation of CD86 and upregulation of programmed death-ligand 1 (PD-L1) in conventional DCs (cDC2 and DC3) and classical monocytes associated with a reduced capacity to stimulate naïve CD4+ T cells correlated with disease severity. Long-lasting depletion and functional impairment of DCs and monocytes may have consequences for susceptibility to secondary infections and therapy of COVID-19 patients.

Improving Drinking and Micturition Habits in Preschool Children: An Educational Project.

INTRODUCTION: Children worldwide often do not drink enough. However, sufficient fluids are essential for physical and cognitive health. A regular and adequate supply of fluids also supports bladder maturation in the context of acquiring urinary continence. We investigated whether training preschool children and their caretakers improves drinking and micturition habits. METHODS: This field study in a pre-post design was conducted in 6 kindergartens in the district of Garmisch-Partenkirchen from October 2018 to February 2019. An intervention group (IG) received a 3-day training on drinking and micturition habits and was compared to a control group (CG) without any training. Caretakers (IG + CG) were instructed about drinking and voiding management, too. Behavioral changes were identified by questionnaires. To analyze the long-term effect, group interviews were performed with the IG 3 months after training. The training was evaluated on different levels. RESULTS: After training, the estimated total daily fluid intake in the IG (1,160 mL) significantly exceeded that of CG (830 mL) (p = 0.015). In the IG, fluid intake until 12:00 a.m. increased (p = 0.001), children took more time for voiding (p = 0.029), and urgency decreased (p = 0.008). Children (IG + CG) used leg support to enable pelvic floor relaxation more often both at home (p = 0.026) and in kindergarten (p = 0.047). Nocturnal enuresis was reduced by approximately 46% in the IG (p = 0.485). Group interviews in the IG showed a considerable learning effect. CONCLUSION: The present study could demonstrate an increased intake of fluids and significant changes in micturition behavior in the IG. So far, this is the first educational project in Germany addressing drinking and voiding management. Our results suggest that a training of preschool children and their caretakers is feasible and effective. Further nationwide research will be needed to confirm our results and assess the need for prevention in these areas.

The use of the online Inverted Classroom Model for digital teaching with gamification in medical studies.

Introduction: In 2014, a newly designed, case-based seminar was successfully implemented in the subjects of health systems, health economics and public health care (GGG). The seminar "The Lonely Patient" is based on a real patient case and deals with the German health care system from the perspective of a patient. In order to create more space for discussion and exchange among students, the seminar was redesigned on the basis of the Inverted Classroom Method (ICM). Project description: Due to the COVID-19 pandemic, new, purely digital teaching formats had to be developed quickly in the sense of Emergency Remote Teaching. Therefore, the Inverted Classroom concept of the seminar was transformed into an online ICM. In order to promote active learning based on the ICAP model (Interactive, Constructive, Active, Passive), the online face-to-face part was designed as a synchronous interactive learner-centered course using the gamified audience response system Kahoot! Results: Evaluation results to date and feedback rounds with students indicate that the online ICM-version of the seminar leads to at least as good evaluation results as the previous face-to-face course. In particular, the students positively emphasize the use of Kahoot! as an activating digital medium. Discussion: Through the use of the ICM and the gamified audience response system Kahoot!, students could be activated in meaningful ways. The resulting discussions about the patient case and teaching content of the quiz questions in the synchronous online course could be implemented just as well as in the classroom-based course of previous semesters. Conclusion: The application of the online ICM, along with the consideration of the ICAP Model, has led to the successful implementation of a digital course within the context of the increased difficulty surrounding the emergency remote teaching. Additionally, students' learning success has remained at a similar level as during traditional classroom-based courses of previous semesters.

Isn't here just there without a "t" - to what extent can digital Clinical Case Discussions compensate for the absence of face-to-face teaching?

Objective: COVID-19 challenges curriculum managers worldwide to create digital substitutes for classroom teaching. Case-based teaching formats under expert supervision can be used as a substitute for practical bedside teaching, where the focus is on teaching clinical reasoning skills. Methods: For medical students of LMU and TU Munich, the interactive, case-based, and supervised teaching format of Clinical Case Discussion (CCD) was digitised and implemented as dCCD in their respective curricula. Case discussions were realised as videoconferences, led by a student moderator, and took place under the supervision of a board-certified clinician. To prevent passive participation, additional cognitive activations were implemented. Acceptance, usability, and subjective learning outcomes were assessed in dCCDs by means of a special evaluation concept. Results: With regard to acceptance, students were of the opinion that they had learned effectively by participating in dCCDs (M=4.31; SD=1.37). The majority of students also stated that they would recommend the course to others (M=4.23; SD=1.62). The technical implementation of the teaching format was judged positively overall, but findings for usability were heterogeneous. Students rated their clinical reasoning skills at the end of the dCCDs (M=4.43; SD=0.66) as being significantly higher than at the beginning (M=4.33; SD=0.69), with low effect size, t(181)=-2.352, p=.020, d=0.15. Conclusion: Our evaluation data shows that the dCCD format is well-accepted by students as a substitute for face-to-face teaching. In the next step, we plan to examine the extent to which participation in dCCDs leads to an increase in objectively measured clinical reasoning skills, analogous to a face-to-face CCD with on-site attendance.

International mobility of students in the medical disciplines from a comparative perspective.

Objective: We analyze the extent to which students of human, veterinary and dental medicine complete study-related stays abroad (frequency, type and duration of stays abroad and countries visited). Furthermore, we investigate the possible correlations between completed stays abroad and the duration of studies, the completion of a doctorate and entering professional life. Methods: The data come from a written cross-sectional survey of 742 graduates of their respective study programs at Bavarian universities. The evaluation was carried out using descriptive and inferential statistical methods. Results: Slightly more than half of the surveyed students completed study-associated stays abroad, with notable differences between the three study programs. The students most frequently completed internships abroad lasting an average of nine weeks. Switzerland was the most common country of destination for the stays abroad. Furthermore, there were no or only weak correlations between stays abroad, the duration of studies and progress towards a doctorate or the commencement of professional employment abroad. There were no correlations with the stress experienced as part of initial employment after graduation. Conclusion: The results clearly indicate that stays abroad are quite usual for students in the medical disciplines and are almost standard in the study of human medicine. The selection of the countries visited indicates that the primary goal of the students' stays abroad is to deepen their competence with a view to later employment in their home country.

Dynamic changes in circulating T follicular helper cell composition predict neutralising antibody responses after yellow fever vaccination.

OBJECTIVES: T follicular helper (Tfh) cells are the principal T helper cell subset that provides help to B cells for potent antibody responses against various pathogens. In this study, we took advantage of the live-attenuated yellow fever virus (YFV) vaccine strain, YF-17D, as a model system for studying human antiviral immune responses in vivo following exposure to an acute primary virus challenge under safe and highly controlled conditions, to comprehensively analyse the dynamics of circulating Tfh (cTfh) cells. METHODS: We tracked and analysed the response of cTfh and other T and B cell subsets in peripheral blood of healthy volunteers by flow cytometry over the course of 4 weeks after YF-17D vaccination. RESULTS: Using surface staining of cell activation markers to track YFV-specific T cells, we found increasing cTfh cell frequencies starting at day 3 and peaking around 2 weeks after YF-17D vaccination. This kinetic was confirmed in a subgroup of donors using MHC multimer staining for four known MHC class II epitopes of YF-17D. The subset composition of cTfh cells changed dynamically during the course of the immune response and was dominated by the cTfh1-polarised subpopulation. Importantly, frequencies of cTfh1 cells correlated with the strength of the neutralising antibody response, whereas frequencies of cTfh17 cells were inversely correlated. CONCLUSION: In summary, we describe detailed cTfh kinetics during YF-17D vaccination. Our results suggest that cTfh expansion and polarisation can serve as a prognostic marker for vaccine success. These insights may be leveraged in the future to improve current vaccine design and strategies.

Complex human adenoid tissue-based ex vivo culture systems reveal anti-inflammatory drug effects on germinal center T and B cells.

BACKGROUND: Human immunology research is often limited to peripheral blood. However, there are important differences between blood immune cells and their counterparts residing in secondary lymphoid organs, such as in the case of germinal center (GC) T follicular helper (Tfh) cells and GC B cells. METHODS: We developed a versatile ex vivo lymphoid organ culture platform that is based on human pharyngeal tonsils (adenoids) and allows for drug testing. We systematically phenotyped Tfh and GC B cell subsets in explant- and suspension cultures using multicolor flow cytometry and cytokine multiplex analysis. FINDINGS: Phenotypic changes of certain ex vivo cultured immune cell subsets could be modulated by cytokine addition. Furthermore, we optimized an activation-induced marker assay to evaluate the response to T cell stimulation. We provide proof-of-concept that Tfh and GC B cells could be modulated in these cultures by different anti-inflammatory drugs in unstimulated states and upon activation with vaccine-derived antigens. For example, GC B cells were lost upon CD40L blockade, and clinically approved JAK inhibitors impacted Tfh and GC B cells, including down-regulation of their key transcription factor BCL6. BCL6 regulation was affected by IL-6 signaling in T cells and IL-4 in B cells, respectively. Furthermore, we demonstrated that JAK signaling and TNF signaling contributed to the stimulation-induced activation of tonsil-derived T cells. INTERPRETATION: Our optimized methods, assays, and mechanistic findings can contribute to a better understanding of human GC responses. These insights may be relevant for improving autoimmune disease therapy and vaccination efficacy. FUNDING: This work was supported by a project grant under the joint research cooperation agreement of LMU Munich, LMU University Hospital, and Sanofi-Aventis Deutschland GmbH, as well as by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - Emmy Noether Programme BA 5132/1-1 and BA 5132/1-2 (252623821), SFB 1054 Project B12 (210592381), and SFB 914 Project B03 (165054336).

Fingolimod Profoundly Reduces Frequencies and Alters Subset Composition of Circulating T Follicular Helper Cells in Multiple Sclerosis Patients.

Fingolimod is an effective treatment for relapsing-remitting multiple sclerosis. It is well established that fingolimod, a modulator of the sphingosine-1-phosphate pathway, restrains the egress of CCR7+ lymphocytes from lymphatic tissues into the blood, thus resulting in reduced lymphocyte counts in peripheral blood. CXCR5+ T follicular helper (Tfh) cells provide help to B cells, are essential for the generation of potent Ab responses, and have been shown to be critically involved in the pathogenesis of several autoimmune diseases. Besides lymphoid tissue-resident Tfh cells, CXCR5+ circulating Tfh (cTfh) cells have been described in the blood, their numbers correlating with the magnitude of Tfh cells in lymphoid tissues. Although the effect of fingolimod on circulating lymphocyte subsets has been established, its effect on cTfh cells remains poorly understood. In this study, we found that although fingolimod strongly and disproportionally reduced cTfh cell frequencies, frequencies of activated cTfh cells were increased, and the composition of the cTfh cell pool was skewed toward a cTfh1 cell phenotype. The circulating T follicular regulatory cell subset and CXCR5+ CD8+ T cell frequencies were also strongly and disproportionally decreased after fingolimod treatment. In contrast, relative frequencies of CXCR5- memory Th cells as well as regulatory T and B cells were increased. In summary, these data provide new insights into fingolimod-induced compositional changes of lymphocyte populations in the blood, in particular cTfh cells, and thus contribute to a better understanding of the mechanism of action of fingolimod in multiple sclerosis patients.

The online inverted classroom model (oICM). A blueprint to adapt the inverted classroom to an online learning setting in medical and health education.

This article was migrated. The article was marked as recommended. The idea of this paper is to offer a blueprint, with that facilitators have a guide to set up a complete digital teaching scenario according to the latest insights of didactical research. The corona pandemic forced higher education institutions all around the world to radically shift their curricula from a mix of face-to-face and remote teaching methods to a fully remote curriculum. Though challenging, this time provides opportunities to implement new educational methods and improve the quality of digital teaching. The classical concept of the inverted classroom was modified to meet the special needs of online settings. The proposed online Inverted Classroom Model (oICM) includes the following phases: (1) pre-phase, (2) self-learning-phase, (3) Synchronous online face-to-face phase, (4) transfer-phase, (5) evaluation. Recommendations and potential tools are provided for each phase. The oICM is an innovative and easy to use approach to shape digital teaching and learning processes during and after the CoVid19 pandemic. This blueprint is developed by the committee "Digitalization" of the German Association for Medical Education (GMA) for facilitators without any prior experience with the ICM, but also for those who already teach in a traditional ICM.