["That One Can See How it is Supposed to be." Conception, Piloting and Evaluation of an Interprofessional Rehabilitation-Related Module for the Training Courses in Medicine, Nursing, and Physiotherapy]. / "Dass man mal sieht, wie es eigentlich sein sollte." Konzeption, Pilotierung und Evaluation eines interprofessionellen rehabilitationsbezogenen Moduls für die Medizin, Pflege und Physiotherapie.

BACKGROUND: Considering the growing rehabilitative care requirements, good interprofessional cooperation is of central relevance for health care professions and is increasingly demanded. Interprofessional cooperation does not yet play a significant role in health professions' education, despite the fact that it is considered an important element of success in outcome- and patient-centered health care. The field of rehabilitation lacks interprofessional teaching concepts and material. METHODS: An interprofessional team of instructors developed the didactic and thematic concept for the module. The module focuses on rehabilitation and discharge management. The learning objectives were developed based on the National Competency-Based Catalogue of Learning Objectives for Medicine. The formative evaluation was based on a questionnaire filled out by the students and the learning guides. RESULTS: 47 participants took part in three runs. The results of the formative evaluation demonstrate that the module was overall well received. The trainees rated the module more favorably than the medical students. While participants emphasized the good practical eye-to-eye interaction between the professions and the honest feedback conversation, they also pointed to the contrast they perceived to their everyday practice. They also wished for more time having verbal interprofessional exchange. The medical students criticized that interprofessional modules were only offered in their final year. CONCLUSION: To the author's knowledge, this is the first publication of an interprofessional module on rehabilitation and discharge management including piloting and positive evaluation for the three professional groups of medicine, nursing and physical therapy. Improvement suggestions of the participants led to modifications that will be realized in the next version of the module. The course sets important impulses for the further development of interprofessional cooperation and the teaching of rehabilitation-related skills. The modular package is available to other lecturers in a free online platform for rehabilitation-related teaching materials.

Glyoxalase 1 expression is downregulated in preimplantation blastocysts of diabetic rabbits.

In a diabetic pregnancy, an altered maternal metabolism led to increased formation of reactive α-dicarbonyls such as glyoxal (GO) and methylglyoxal (MGO) in the reproductive organs and embryos. The enzyme glyoxalase (GLO) 1 detoxifies reactive α-dicarbonyls thus protecting cells against malfunction or modifications of proteins by advanced glycated end products (AGEs). The aim of this study was to analyse the influence of a maternal insulin-dependent diabetes mellitus (IDD) on GLO1 expression and activity in preimplantation embryos in vivo and human trophoblast cells (Ac-1M88) in vitro. Maternal diabetes was induced in female rabbits by alloxan before conception and maintained during the preimplantation period. GLO1 expression and activity were investigated in 6-day-old blastocysts from healthy and diabetic rabbits. Furthermore, blastocysts and human trophoblast cells were exposed in vitro to hyperglycaemia, GO and MGO and analysed for GLO1 expression and activity. During gastrulation, GLO1 was expressed in all compartments of the rabbit blastocyst. Maternal diabetes decreased embryonic GLO1 protein amount by approx. 30 per cent whereas the enzymatic activity remained unchanged, indicating that the specific GLO1 activity increases along with metabolic changes. In in vitro cultured embryos, neither hyperglycaemia nor MGO and GO had an effect on GLO1 protein amount. In human trophoblast cells, a stimulating effect on the GLO1 expression was shown in the highest GO concentration, only. Our data show that maternal diabetes mellitus affects the specific activity of GLO1, indicating that GLO1 was post-translationally modified due to changes in metabolic processes in the preimplantation embryos.

Cholesterol metabolism in rabbit blastocysts under maternal diabetes.

In the rabbit reproductive model, maternal experimentally induced insulin-dependent diabetes mellitus (expIDD) leads to accumulation of lipid droplets in blastocysts. Cholesterol metabolism is a likely candidate to explain such metabolic changes. Therefore, in the present study we analysed maternal and embryonic cholesterol concentrations and expression of related genes in vivo (diabetic model) and in vitro (embryo culture in hyperglycaemic medium). In pregnant expIDD rabbits, the serum composition of lipoprotein subfractions was changed, with a decrease in high-density lipoprotein cholesterol and an increase in very low-density lipoprotein cholesterol; in uterine fluid, total cholesterol concentrations were elevated. Expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), very low-density lipoprotein receptor (VLDLR), sterol regulatory element binding transcription factor 2 (SREBF2), insulin-induced gene-1 (INSIG1) and cholesterol 7α-hydroxylase (CYP7A1) mRNA was decreased in the liver and low-density lipoprotein receptor (LDLR) mRNA expression was decreased in the adipose tissue of diabetic rabbits. In embryos from diabetic rabbits, the mean (±s.e.m.) ratio of cholesterol concentrations in trophoblasts to embryoblasts was changed from 1.27±2.34 (control) to 0.88±3.85 (expIDD). Rabbit blastocysts expressed HMGCR, LDLR, VLDLR, SREBF2 and INSIG1 but not CYP7A1, without any impairment of expression as a result of maternal diabetes. In vitro hyperglycaemia decreased embryonic HMGCR and SREBF2 transcription in rabbit blastocysts. The findings of the present study show that a diabetic pregnancy leads to distinct changes in maternal cholesterol metabolism with a minor effect on embryo cholesterol metabolism.

The Long-Term Effect of the Periconception Period on the Embryo's Epigenetic Profile and Phenotype: The Role of Maternal Disease Such as Diabetes and How the Effect Is Mediated (Example from a Rabbit Model).

Maternal metabolic diseases such as diabetes mellitus with diabetogenic hypoinsulinemia and hyperglycemia change periconceptional developmental conditions in utero. In preimplantation rabbit embryos, all major metabolic pathways are affected. Alterations in protein, lipid and glucose metabolism, adipokines, advanced glycation end products (AGEs) and reactive oxygen species (ROS) are described in this review. The embryonic metabolism is characterized by a high plasticity which enables survival of most preimplantation embryos under the non-physiological developmental conditions in diabetic mothers. Adiponectin, for example, compensates for the missing insulin-driven glucose supply and stimulates intracellular lipid accumulation in embryonic cells. AGEs and ROS are clear indicators of metabolic stress. The price paid for survival, however, needs to be taken into consideration. It is an increase in lipogenesis and proteinogenesis, leading to metabolic stress and with potentially negative long-term health effects.

Accumulation of advanced glycation end products in the rabbit blastocyst under maternal diabetes.

Diabetes mellitus (DM) during pregnancy is one of the leading causes of perinatal morbidity and birth defects. The mechanism by which maternal hyperglycemia, the major teratogenic factor, induces embryonic malformations remains unclear. Advanced glycation end products (AGEs) are known to accumulate during the course of DM and contribute to the development of diabetic complications. Employing a diabetic rabbit model, we investigated the influence of maternal hyperglycemia during the preimplantation period on AGE formation (pentosidine, argpyrimidine, and N(ϵ)-carboxymethyllysine (CML)) in the reproductive tract and the embryo itself. As a consequence of type 1 DM, the AGE levels in blood plasma increased up to 50%, correlating closely with an AGE accumulation in the endometrium of diabetic females. Embryos from diabetic mothers had increased protein-bound CML levels and showed enhanced fluorescent signals for AGE-specific fluorescence in the blastocyst cavity fluid (BCF). The quantification of CML by HPLC-mass spectrometry (MS/MS) showed a higher amount of soluble CML in the BCF of blastocysts from diabetic rabbits (0.26±0.05 µmol/l) compared with controls (0.18±0.02 µmol/l). The high amount of AGEs in blastocysts from diabetic mothers correlates positively with an increased AGER (receptor for AGE (RAGE)) mRNA expression. Our study gives alarming insights into the consequences of poorly controlled maternal diabetes for AGE formation in the embryo. Maternal hyperglycemia during the preimplantation period is correlated with an increase in AGE formation in the uterine environment and the embryo itself. This may influence the development of the embryo through increased AGE-mediated cellular stress by RAGEs.

Glycation of extracellular matrix proteins impairs migration of immune cells.

The immune response during aging and diabetes is disturbed and may be due to the altered migration of immune cells in an aged tissue. Our study should prove the hypothesis that age and diabetes-related advanced glycation end products (AGEs) have an impact on the migration and adhesion of human T-cells. To achieve our purpose, we used in vitro AGE-modified proteins (soluble albumin and fibronectin [FN]), as well as human collagen obtained from bypass graft. A Boyden chamber was used to study cell migration. Migrated Jurkat T-cells were analyzed by flow cytometry and cell adhesion by crystal violet staining. Actin polymerization was determined by phalloidin-Alexa-fluor 488-labeled antibody and fluorescence microscopy. We found that significantly fewer cells (50%, p = 0.003) migrated through methylglyoxal modified FN. The attachment to FN in the presence of AGE-bovine serum albumin (BSA) was also reduced (p < 0.05). In ex vivo experiments, isolated collagen from human vein graft material negatively affected the migration of the cells depending on the grade of AGE modification of the collagen. Collagen with a low AGE level reduced the cell migration by 30%, and collagen with a high AGE level by 60%. Interaction of the cells with an AGE-modified matrix, but not with soluble AGEs like BSA-AGE per se, was responsible for a disturbed migration. The reduced migration was accompanied by an impaired actin polymerization. We conclude that AGEs-modified matrix protein inhibits cell migration and adhesion of Jurkat T-cells.

["Halle surgery week": how a teaching format awakens medical students' interest in surgery]. / "Hallesche OP-Wochen": Wie ein Lehrformat das Interesse von Medizinstudierenden an der Chirurgie weckt.

BACKGROUND: A practical education in surgery is difficult to conduct in a student-centered manner and is thus often inadequate. New teaching concepts are required to provide students with insights into surgery and make the field more appealing. METHODS: As part of a two-week facultative event, medical students followed eight live surgical procedures from different disciplines from an auditorium. In the auditorium, the procedures were simultaneously moderated by an experienced surgeon. Before and after every procedure, questionnaires were used to analyze whether the teaching event was suited to improve an understanding and interest for the field of surgery. RESULTS: A total of 709 completed questionnaires (pre and post) from 381 students were collected. The self-reported learning effect was evaluated as good or very good by students. In many of the presented disciplines, experiencing a live surgical procedure was associated with significant positive changes in attitude regarding each discipline in general, a potential clinical traineeship in the discipline and choosing the discipline as a later specialization. CONCLUSION: The high attendance as well as the evaluation results suggest a high acceptance for the teaching event. The teaching format is suited to improve the understanding of surgical procedures and had a positive effect on medical students' attitude towards surgical disciplines.

Application of telepresence systems in teaching - transfer of an interprofessional teaching module on digital aided communication into the block training "internal medicine" during the Covid-19 pandemic.

Objective: The contact restrictions caused by the Covid-19 pandemic fundamentally limit patient-centered teaching. To realize a patient-oriented education in the block training "Internal Medicine" at the University Hospital Halle (Saale) despite the challenges, the already established teaching module "Interprofessional Teleconsultation" was adapted. The short article outlines the interprofessional teaching module including first evaluation results and describes the adapted block training. Method: In the "Internal Medicine" block training, students in a lecture hall navigated a telepresence system, which was accompanied by a physician across the ward and conducted an anamnesis via video and audio transmission without actual patient contact. Results: Students, physicians, and patients were open-minded about this form of communication during the Covid-19 pandemic and quickly got accustomed to the use of the telepresence system. To be able to react to technical challenges (e.g. unstable connection between the communication partners), a careful preparation of the lecturers is necessary. Conclusion: In using a telepresence system, patient-oriented teaching of students in the block training "Internal Medicine" can be ensured with low-threshold technical effort during the Covid-19 pandemic. The telepresence system allows for the involvement of patients into teaching while adhering to the necessary hygiene measures. Despite technical challenges, the teaching format based on telepresence is suitable as an alternative to face-to-face teaching if actual patient contact is not possible.

Comparative Analysis of AGE and RAGE Levels in Human Somatic and Embryonic Stem Cells under H2O2-Induced Noncytotoxic Oxidative Stress Conditions.

The accumulation of advanced glycation end products (AGEs) occurs in ageing and in many degenerative diseases as a final outcome of persistent oxidative stress on cells and organs. Environmental alterations taking place during early embryonic development can also lead to oxidative damage, reactive oxygen species (ROS) production, and AGE accumulation. Whether similar mechanisms act on somatic and embryonic stem cells (ESC) exposed to oxidative stress is not known; and therefore, the modelling of oxidative stress in vitro on human ESC has been the focus of this study. We compared changes in N ε -carboxymethyl-lysine (CML) advanced glycation end products and RAGE levels in hESC versus differentiated somatic cells exposed to H2O2 within the noncytotoxic range. Our data revealed that hESC accumulates CML and RAGE under oxidative stress conditions in different ways than somatic cells, being the accumulation of CML statistically significant only in somatic cells and, conversely, the RAGE increase exclusively appreciated in hESC. Then, following cardiac and neural differentiation, we observed a progressive removal of AGEs and at the same time an elevated activity of the 20S proteasome. We conclude that human ESCs constitute a unique model to study the consequence of an oxidative environment in the pluripotent cells of the embryo during the human preimplantation period.

Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy.

During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA) metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. In the cavity fluid of blastocysts from diabetic rabbits BCAA concentrations were twice as high as those from controls, indicating a close link between maternal diabetes and embryonic BCAA metabolism. The expression of BCAA oxidizing enzymes and BCAA transporter was analysed in maternal tissues and in blastocysts. The RNA amounts of three oxidizing enzymes, i.e. branched chain aminotransferase 2 (Bcat2), branched chain ketoacid dehydrogenase (Bckdha) and dehydrolipoyl dehydrogenase (Dld), were markedly increased in maternal adipose tissue and decreased in liver and skeletal muscle of diabetic rabbits than in those of controls. Blastocysts of diabetic rabbits revealed a higher Bcat2 mRNA and protein abundance in comparison to control blastocysts. The expression of BCAA transporter LAT1 and LAT2 were unaltered in endometrium of diabetic and healthy rabbits, whereas LAT2 transcripts were increased in blastocysts of diabetic rabbits. In correlation to high embryonic BCAA levels the phosphorylation amount of the nutrient sensor mammalian target of rapamycin (mTOR) was enhanced in blastocysts caused by maternal diabetes. These results demonstrate a direct impact of maternal diabetes on BCAA concentrations and degradation in mammalian blastocysts with influence on embryonic mTOR signalling.

Role of advanced glycation end products in cellular signaling.

Improvements in health care and lifestyle have led to an elevated lifespan and increased focus on age-associated diseases, such as neurodegeneration, cardiovascular disease, frailty and arteriosclerosis. In all these chronic diseases protein, lipid or nucleic acid modifications are involved, including cross-linked and non-degradable aggregates, such as advanced glycation end products (AGEs). Formation of endogenous or uptake of dietary AGEs can lead to further protein modifications and activation of several inflammatory signaling pathways. This review will give an overview of the most prominent AGE-mediated signaling cascades, AGE receptor interactions, prevention of AGE formation and the impact of AGEs during pathophysiological processes.

Maternal diabetes leads to unphysiological high lipid accumulation in rabbit preimplantation embryos.

According to the "developmental origin of health and disease" hypothesis, the metabolic set points of glucose and lipid metabolism are determined prenatally. In the case of a diabetic pregnancy, the embryo is exposed to higher glucose and lipid concentrations as early as during preimplantation development. We used the rabbit to study the effect of maternal diabetes type 1 on lipid accumulation and expression of lipogenic markers in preimplantation blastocysts. Accompanied by elevated triglyceride and glucose levels in the maternal blood, embryos from diabetic rabbits showed a massive intracellular lipid accumulation and increased expression of fatty acid transporter 4, fatty acid-binding protein 4, perilipin/adipophilin, and maturation of sterol-regulated element binding protein. However, expression of fatty acid synthase, a key enzyme for de novo synthesis of fatty acids, was not altered in vivo. During a short time in vitro culture of rabbit blastocysts, the accumulation of lipid droplets and expression of lipogenic markers were directly correlated with increasing glucose concentration, indicating that hyperglycemia leads to increased lipogenesis in the preimplantation embryo. Our study shows the decisive effect of glucose as the determining factor for fatty acid metabolism and intracellular lipid accumulation in preimplantation embryos.