Accuracy of controlled attenuation parameter measurement for the detection of steatosis in autoimmune liver diseases.

Background & Aims: Concurrent fatty liver disease represents an emerging challenge in the care of individuals with autoimmune liver diseases (AILD). Therefore, we aimed to validate the ultrasound-based method of controlled-attenuation parameter (CAP) as a non-invasive tool to detect hepatic steatosis in individuals with AILD. Methods: The diagnostic performance of CAP to determine biopsy-proven hepatic steatosis (>5%) was assessed in individuals with AILD (autoimmune hepatitis [AIH], primary biliary cholangitis [PBC], primary biliary cholangitis [PSC], or variant syndromes) who underwent liver biopsy at the University Medical Center Hamburg-Eppendorf between 2015-2020 by calculating the area under the receiver operating characteristic (AUROC) curves. In AIH, the impact of disease activity was evaluated by assessment of CAP upon resolution of hepatic inflammation during follow-up. Results: Overall, 433 individuals with AILD (AIH: 218, PBC: 51, PSC: 85, PBC/AIH: 63, PSC/AIH: 16) were included. Histologically proven steatosis was present in 90 individuals (20.8%). Steatosis was less frequently observed in people with PSC (14%) than in other AILD. CAP values correlated positively with grade of steatosis (ρ = 0.39) and the BMI (ρ = 0.53). In PBC and PSC, the ROC curves defined an AUROC of 0.81 and 0.93 for detecting steatosis at an optimal cut-off of 276 dB/m (sensitivity: 0.71; specificity: 0.82) and 254 dB/m (sensitivity: 0.91, specificity: 0.85), respectively. In AIH, the diagnostic performance of CAP was significantly lower (AUROC = 0.72, p = 0.009). However, resolution of hepatic inflammation under treatment was associated with a significant increase in CAP levels (median [IQR]: +38.0 [6-81] dB/m) and considerably improved diagnostic accuracy (AUROC = 0.85; cut-off: 288 dB/m; sensitivity: 0.67, specificity: 0.90). Conclusions: In PBC and PSC, hepatic steatosis can be reliably detected by applying disease-specific thresholds of CAP. In AIH, the diagnostic accuracy of CAP is moderate at diagnosis, but improves after acute hepatitis has resolved. Impact and implications: Non-invasive estimation of fat content in the liver can be performed with the ultrasound-based method of controlled-attenuation parameter (CAP). Here, we showed that the presence of a concomitant fatty liver is frequent in people with autoimmune liver diseases and we determined disease-specific thresholds of CAP to best predict the presence of a fatty liver. CAP measurement was shown to be a valid tool to detect fatty liver in individuals with PSC and PBC; however, in AIH, CAP had limited accuracy especially when significant inflammatory activity was present in the liver. In the context of substantial liver inflammation, therefore, CAP values should be interpreted with caution, and measurements should be repeated after acute hepatitis has resolved.

Immersive medium for early clinical exposure - knowledge acquisition, spatial orientation and the unexpected role of annotation in 360° VR photos.

Aim: 360° VR photos could be a low-threshold possibility to increase early clinical exposure. Apart from granting insights into local routines and premises, the medium should facilitate knowledge acquisition and spatial orientation depending on its design. This assumption, however, is not yet substantiated empirically. Thus, three hypotheses were tested in consideration of Mayer's modality principle: 1) Providing 360° VR photos as visual reference improves retention and comprehension of information. 2) The annotation of text boxes in 360° VR photos compromises spatial orientation and presence. 3) Annotated audio commentary is superior to annotated text boxes in terms of cognitive load and knowledge acquisition. Methods: Using head-mounted displays, students of human (N=53) and dental medicine (N=8) completed one of three virtual tours through a surgical unit, which were created with 360° VR photos. In the first two variants, information about the facilities, medical devices and clinical procedures was annotated either as text boxes or audio commentary comprising 67 words on average (SD=6.67). In the third variant, the same information was given separately on a printed handout before the virtual tour. Taking user experience and individual learner characteristics into account, differences between conditions were measured regarding retention, comprehension, spatial orientation, cognitive load, and presence. Results: Concerning retention and comprehension of information, annotated text boxes outperformed annotated audio commentary and the handout condition. Although annotated audio commentary exhibited the lowest knowledge test scores, students preferred listening over reading. Students with an interest in VR and 360° media reported higher levels of enjoyment and presence. Regarding spatial orientation and presence, no significant group differences were found. Conclusions: 360° VR photos can convey information and a sense of spatial orientation effectively in the same learning scenario. For students, their use is both enjoyable and instructive. Unexpectedly, the ideal mode of annotation is not dictated by Mayer's modality principle. For information like in this study, annotated text boxes are better for knowledge acquisition than the subjectively preferred audio commentary. This finding is probably contingent on the length and the quality of the annotated text. To identify boundary conditions and to validate the findings, more research is required on the design and educational use of 360° VR photos.

Did video kill the XR star? Digital trends in medical education before and after the COVID-19 outbreak from the perspective of students and lecturers from the faculty of medicine at the University of Ulm.

Aim: Using a comparison of digital teaching in medicine before and after the COVID-19 outbreak, the aim of the study was to examine how ad hoc digitization has changed (1) the design of digital teaching, (2) the attitudes toward and the capabilities of digital teaching and learning and (3) the future importance of individual digital teaching elements. Methods: Students and lecturers from the Medical Faculty of Ulm were asked to voluntarily participate in online surveys during the summer semesters of 2019 and 2020. The data was subsequently analyzed from a longitudinal and cross-sectional view descriptively as well as by using t-tests and Chi2-tests. In addition, using regression analyses, the results were controlled for associations with age, study progress, and media affinity. Results: In the summer semester 2019, 163 students (6.1% response rate) and 56 lecturers (11.5%) participated in the surveys. In the following year, the participation increased to 285 students (10.4%) and 64 lecturers (12.8%). Video-based teaching elements such as videoconferencing and lecture recordings were increasingly used after the COVID-19 outbreak and considered more significant for future teaching. In contrast, virtual reality, augmented reality and 360°-videos, grouped under the term extended reality (XR), are descriptively becoming less important. Most lecturers would like to teach more digitally even after the pandemic but fear a decrease in learning effectiveness and contact with students, who tend to prefer asynchronous learning opportunities. Conclusion: Video-based teaching elements proved to be a low-threshold and time-efficient solution during the lockdown and were also recommended for future use. The XR technology has been put on the back burner for the time being, but in view of the increased digital teaching motivation and capabilities, it can be assumed that lecturers will recognize and use the potential of XR as soon as they have the freedom to design innovative teaching again.

The Use of a Mobile Learning Tool by Medical Students in Undergraduate Anatomy and its Effects on Assessment Outcomes.

Hand-held devices have revolutionized communication and education in the last decade. Consequently, mobile learning (m-learning) has become popular among medical students. Nevertheless, there are relatively few studies assessing students' learning outcomes using m-learning devices. This observational study presents an anatomy m-learning tool (eMed-App), an application developed to accompany an anatomy seminar and support medical students' self-directed learning of the skeletal system. Questionnaire data describe where, how frequently, and why students used the app. Multiple choice examination results were analyzed to evaluate whether usage of the app had an effect on test scores. The eMed-App application was used by 77.5% of the students, mainly accessed by Android smartphones, and at students' homes (62.2%) in order to prepare themselves for seminar sessions (60.8%), or to review learning content (67%). Most commonly, students logged on for less than 15 minutes each time (67.8%). Frequent app users showed better test results on items covering eMed-App learning content. In addition, users also achieved better results on items that were not related to the content of the app and, thus, gained better overall test results and lower failure rates. The top quartile of test performers used the eMed-App more frequently compared to students in lower quartiles. This study demonstrated that many students, especially the high-performing ones, made use of the eMed-App. However, the app itself did not result in better outcomes, suggesting that top students might have been more motivated to use the app than students who were generally weak in anatomy.

[Augmented Reality in Ophthalmology: Technical Innovation Complements Education for Medical Students]. / Augmented Reality in der Augenheilkunde: Technische Innovation ergänzt studentische Lehre.

BACKGROUND: At the Medical Faculty of the University of Ulm, the learning objectives of ophthalmology are taught to students in a one-week block course in the fourth year of study. According to the National Competency-based Learning Objective Catalogue Medicine (NKLM), one of these learning objectives is the clinical examination of the eye, including the eye fundus examination. In order to best train this expertise as defined in the NKLM, a novel, augmented reality-based training simulator (Eyesi Indirect, VRmagic Holding AG, Mannheim, Germany) was integrated into the teaching at the University Eye Hospital Ulm. During the block week, two key questions were examined: Does the one week block lesson increase interest in ophthalmology? How do students assess the use of an innovative e-learning technology compared to three other classical teaching methods for learning ophthalmoscopy? MATERIAL/METHODS: As part of the student teaching (block weeks July and October 2016), 292 students were questioned by questionnaire anonymously and on a voluntary basis regarding their assessment of the block week and the training simulator at the beginning and end of the one week event. The ophthalmoscopies were classically practiced on the ophthalmoscope trainer, head model and on fellow students and then performed on the new training simulator. RESULTS: Overall, there was little interest among the students in ophthalmology. However, the block week helped to increase interest (p < 0.001). The assessments of attractiveness before and after the block week of ophthalmology as a later professional goal and as an optional subject in the practical year were also significantly increased (p < 0.001 or p = 0.031). With regard to the use of e-learning technologies, it was shown that the handling of the simulator for learning ophthalmoscopy was rated more attractive by the students than the classical technology-based teaching methods (all p < 0.01). The joy of learning could only be further increased by practicing on a fellow student (p = 0.051). CONCLUSION: The results of the present study show a positive impact of the block week on the attractiveness assessment of the specialty by the participating students. Innovative e-learning methods can increase the enjoyment of learning. However, the training simulator cannot provide a complete replacement of the training on a real person.

How do German medical students perceive role models during clinical placements ("Famulatur")? An empirical study.

BACKGROUND: Studies have demonstrated the importance of role models in medical education. Medical students in Germany participate in clinical placements ("Famulatur") that last 4 months in total and represent the first real-world setting where students encounter possible role models in their clinical education. These placements are an extracurricular activity, however, and regarded as the "black box" of medical education. This study aimed to evaluate whether and how students experience role models during clinical placements, the qualities associated with potential role models and whether role model-related learning gains are relevant. METHODS: We recruited 96 students (mean age: 23.83 years; 75% female) in their 5th to 9th semesters at the Faculty of Medicine at the University of Ulm, Germany, who were participating in a clinical placement between July and October 2015. Participants completed a questionnaire at the beginning of a 5-day working week to record sociodemographic and other information and another one at the end of the week to assess various aspects of their experiences. On each of the 5 days, they completed a structured questionnaire to record their perceived role models and self-assessed learning gains. RESULTS: Role models and role modelling play an important role in clinical placements. The positive function of medical staff as role models predominated (88.4%) across all specialties. Junior doctors were the most frequently perceived role models (28.5%), followed by consultants (25.1%) and nursing staff (22.4%). The most commonly perceived positive quality was the interaction with students (16.5%), followed by team behaviour (13.6%), interaction with patients (13.6%) and professional expertise (13.4%). Students also had various kinds of learning gains such as knowledge or skills. CONCLUSIONS: Although these clinical placements are extracurricular activities in Germany and their content is not regulated, they are home to a relevant amount of role modelling. Students experience the various medical professions in different roles and in a range of tasks and interactions. Defining basic learning objectives could help to increase the relevance of these placements for the medical curriculum in Germany and transfer the associated learning gains from the hidden to the open curriculum.

[Innovative Teaching Methods: Wet Lab-based Ophthalmosurgical Education for Medical Students]. / Innovative Lehrmethoden: Einsatz eines ophthalmochirurgischen Wetlabs im Studentenunterricht.

BACKGROUND: An increased demand for young physicians in Germany is causing increased competition to attract the best minds, even during their undergraduate studies. Therefore, it is the task of the university hospitals to offer their students the best possible courses in order to arouse interest in the relevant subject area. We therefore examined the impact of an ophthalmosurgical wet lab on teaching undergraduate medical students. MATERIAL/METHODS: Undergraduate medical students were offered voluntary participation in the ophthalmosurgical wet lab during an ophthalmology block week. At the beginning and at the end of the week, as well as at the end of the wet lab, the students answered questionnaires with questions about the interest in the field of ophthalmology and the specific assessment of the wet lab. RESULTS: The interest of the students in ophthalmology was increased by the block week and additionally by the wet lab. The wet lab enriched the block week and was rated as very good by the participants. The overall rating of the block week was significantly better among participants in the wet lab than in the group without wet lab participation. The wet lab gave the students great pleasure, enabled them to apply the acquired knowledge, gain valuable insights into ophthalmology, and was easily implemented. CONCLUSION: The integration of a wet lab into the block week was evaluated very positively by the students and gives them a valuable insight into the field of ophthalmology.

Potential impact of screening for fatty liver disease by transient elastography with liver stiffness and controlled attenuation parameter measurements: a pilot study.

Background The prevalence of chronic liver diseases is high in developed countries, and the leading causes are amenable to prevention. The German Lebertag is to increase awareness of the burden of chronic liver diseases in the general public. We performed a pilot study using transient elastography with liver stiffness measurement (LSM) and the controlled attenuation parameter (CAP) as a screening tool for previously unrecognized liver diseases. Patients and methods LSM and CAP was performed in 60 individuals, and participants filled in a questionnaire reporting basic characteristics and past medical history. Results Median LSM and CAP values were within the normal range. Participants with self-reported diabetes mellitus had significantly elevated LSM (p = 0.02) and CAP values (p = 0.002). Participants with a BMI > 30 kg/m2 or dyslipidemia had significantly elevated CAP values (p = 0.007 and p = 0.01, respectively) with normal LSM values. Overall, 35 % of participants had elevated CAP values, indicating a high prevalence of hepatic steatosis. Discussion In a German pilot study, diabetes mellitus was a key risk factor for increased LSM and CAP values. Prevalence of steatosis was high and comparable to other Western countries. Transient elastography is a valuable tool to identify patients with increased risk for metabolic liver diseases. In people without risk factors, LSM and CAP values were within the normal range, indicating that screening for chronic liver injury was not warranted.

Membrane translocation of binary actin-ADP-ribosylating toxins from Clostridium difficile and Clostridium perfringens is facilitated by cyclophilin A and Hsp90.

Some hypervirulent strains of Clostridium difficile produce the binary actin-ADP-ribosylating toxin C. difficile transferase (CDT) in addition to Rho-glucosylating toxins A and B. It has been suggested that the presence of CDT increases the severity of C. difficile-associated diseases, including pseudomembranous colitis. CDT contains a binding and translocation component, CDTb, that mediates the transport of the separate enzyme component CDTa into the cytosol of target cells, where CDTa modifies actin. Here we investigated the mechanism of cellular CDT uptake and found that bafilomycin A1 protects cultured epithelial cells from intoxication with CDT, implying that CDTa is translocated from acidified endosomal vesicles into the cytosol. Consistently, CDTa is translocated across the cytoplasmic membranes into the cytosol when cell-bound CDT is exposed to acidic medium. Radicicol and cyclosporine A, inhibitors of the heat shock protein Hsp90 and cyclophilins, respectively, protected cells from intoxication with CDT but not from intoxication with toxins A and B. Moreover, both inhibitors blocked the pH-dependent membrane translocation of CDTa, strongly suggesting that Hsp90 and cyclophilin are crucial for this process. In contrast, the inhibitors did not interfere with the ADP-ribosyltransferase activity, receptor binding, or endocytosis of the toxin. We obtained comparable results with the closely related iota-toxin from Clostridium perfringens. Moreover, CDTa and Ia, the enzyme component of iota-toxin, specifically bound to immobilized Hsp90 and cyclophilin A in vitro. In combination with our recently obtained data on the C2 toxin from C. botulinum, these results imply a common Hsp90/cyclophilin A-dependent translocation mechanism for the family of binary actin-ADP-ribosylating toxins.

Sequência e cronologia de erupção dos dentesdecíduos em crianças do município de Itajaí (SC) / Sequence and chronology of eruption ofdeciduous teeth in children from Itajaí city (SC)

Introdução: Variáveis nutricionais e de desenvolvimento no nascimentoe na vida precoce podem predizer o número de dentes erupcionados queas crianças têm em sua cavidade oral. Objetivo: Verificar a cronologiae a sequência de erupção dental decídua de crianças do município deItajaí, confrontando dados referentes a elementos dentais, gênero, idade,nível socioeconômico e amamentação. Material e métodos: Realizouseum estudo transversal com 1.297 crianças divididas pelo gênero epela idade. Para testar a hipótese de que a erupção dental decídua variaem cada dente para o sexo masculino e feminino, comparativamente,utilizou-se o teste t. Resultados: Observou-se início mais precoceda erupção nos meninos com o dente 61 (incisivo central superioresquerdo), aos 10,6 meses, e término com o dente 65 (segundo molarsuperior esquerdo), aos 30,9 meses. As meninas começaram a erupçãodental com o dente 71 (incisivo central inferior esquerdo) aos 12 mesese terminaram com o dente 85 (segundo molar inferior direito) aos 31,55meses. Houve variação na análise das médias de erupção pelo teste t entre os gêneros para os dentes 63, 72, 73 e 83. O tempo médio deerupção para o sexo masculino foi de 20,30 meses e para o feminino foide 19,55. Verificaram-se médias de erupção maiores estatisticamenteinsignificantes nas crianças que receberam amamentação além dos6 meses de idade. Conclusão: Tais valores pressupõem que, assimcomo a sequência, o tempo médio de erupção dental é determinadogeneticamente. Influências ambientais, como tipo de amamentação,não alteram as médias de erupção.

Introduction: Nutritional and development variables both at birth andearly age can predict the number of erupted teeth that children willhave in their oral cavity. Objective: This study aimed to report the timeand sequence of eruption of deciduous teeth in children from Itajaí city,comparing data regarding to teeth, gender, age, socioeconomic level,and breast-feeding. Material and methods: A cross-sectional studywas performed with 1297 children divided by gender and age. In orderto test the hypothesis that tooth eruption varies between males andfemales, t-test was comparatively applied. Results: It was observedan earlier male eruption time of tooth #61 (left upper central incisor),starting at 10.6 months and finishing at 30.9 months, with tooth #65(left upper second molar). Female eruption time started with tooth#71 (left lower central incisor), at 12 months and finished at 31.55months with tooth #85 (right lower second molar). The analysis ofmean eruption values by t-test showed a contrast between genders forthe following teeth: #63, #72, #73, and #83. Total male and femalemean eruption time was 20.30 months and 19.95 months, respectively.It was observed that children who had been exclusively breastfed forover than six months, showed non-statistically significant greater meaneruption times Conclusion: Such values predict that both sequence andmean eruption time would be genetically determined. Environmentalinfluences as breast-feeding type do not necessarily alter the eruptiontime means.

Avaliação clínica da atividade dos músculos mastigatórios durante a mastigação habitual - um estudo sobre a normalização de dados eletromiográficos / Clinical evaluation of masticatory muscles activity during habitual mastication: a study about normalization of electromyographic data

Este estudo tem como objetivo comparar, qualitativa e quantitativamente, a amplitude eletromiográfica normalizada e não normalizada (dados absolutos) dos músculos mastigatórios de mulheres sintomáticas e assintomáticas para a disfunção temporomandibular (DTM). Foi analisada a atividade eletromiográfica dos músculos masseter e temporal (parte anterior), durante a mastigação habitual, de 41 mulheres, sendo 20 sintomáticas e 21 assintomáticas para a DTM. Após a normalização pela Contração Isométrica Voluntária Submáxima, os dados foram comparados com base no Teste de Wilcoxon. O nível de significância ficou estabelecido em 5%. Quando comparados os dados absolutos, notou-se que, a atividade do músculo masseter foi significativamente menor no Grupo DTM em relação à do Grupo Controle. Depois da normalização das informações, não foram verificadas diferenças entre os dois grupos mencionados. De acordo com os resultados obtidos, pode-se sugerir que, os dados absolutos podem representar achados clínicos, observados na análise qualitativa do sinal eletromiográfico.

The aim of this study was to compare qualitatively and quantitatively the normalized and non-normalized (raw data) EMG amplitude of masticatory muscles between women symptomatic and asymptomatic for temporomandibular disorders (TMD). The electromyographic activity of masseter and anterior temporal muscle of 41 women was analyzed (20 symptomatic and 21 asymptomatic for TMD) during the mastication. After normalization by the Submaximal Voluntary Isometric Contraction, the data were compared by Wilcoxon test. The significance level was set at 5%. When the electromyographic absolute data were compared, masseter muscle activity was significantly lower in TMD Group than in Control Group. After normalization of the data, there were not observed differences between these groups. According to the results obtained, it can be suggested that the raw EMG data can represent clinical findings observed in qualitative analysis of the EMG signal.

Cyclophilin A facilitates translocation of the Clostridium botulinum C2 toxin across membranes of acidified endosomes into the cytosol of mammalian cells.

The binary Clostridium botulinum C2 toxin consists of the binding/translocation component C2IIa and the separate enzyme component C2I, which mono-ADP-ribosylates actin in eukaryotic cells. Pore formation of C2IIa in early endosomal membranes facilitates translocation of unfolded C2I into the cytosol. We discovered earlier that translocation of C2I depends on the activity of the host cell chaperone heat shock protein Hsp90. Here, we demonstrate that cyclosporin A, which inhibits the peptidyl-prolyl cis/trans isomerase activity of cyclophilins, inhibited intoxication of cells with C2 toxin and prevented uptake of C2I into the cytosol. Cyclosporin A blocked the pH-dependent translocation of C2I activity across membranes of intact cells and of partially purified early endosomes. In vitro, the addition of cytosol to C2 toxin-loaded endosomes induced translocation of C2I activity into the cytosol, which was prevented by pretreatment of the cytosol with an antibody against cyclophilin A. Pull-down experiments with lysates from C2 toxin-treated cells revealed specific binding of cyclophilin A to the N-terminal domain of C2I. In conclusion, our results suggest an essential role of cyclophilin A for translocation of C2I across endosomal membranes during the uptake of C2 toxin into mammalian cells.