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Sophie de Boer,1,2 Felix Klewitz,1,2 Maximilian Bauer-Hohmann,1,2 Lena Schiffer,2,3 Uwe Tegtbur,2,4 Lars Pape,2,3 Mario Schiffer,2,5,6 Martina de Zwaan,1,2 Mariel Nöhre1,2 1Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Hannover, Germany; 2Project Kidney Transplantation 360° (NTx360°), Hannover Medical School, Hannover, Germany; 3Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany; 4Department of Sports Medicine, Hannover Medical School, Hannover, Germany; 5Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany; 6Department of Nephrology and Hypertension, Hannover Medical School, Hannover, GermanyCorrespondence: Mariel Nöhre Department of Psychosomatic Medicine and PsychotherapyHannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, GermanyTel +49 511 532 3932Fax +49 511 532 3190Email noehre.mariel@mh-hannover.dePurpose: After organ transplantation, adherence to immunosuppressive medication (ISM) is crucial to prevent organ rejection. To enable adherence, patients need to be well informed about the different aspects associated with their ISM. However, literature suggests that knowledge regarding ISM is often inadequate.Patients and Methods: In a cross-sectional study, 702 patients after kidney transplantation participating in a structured multimodal follow-up program (KTx360°) were evaluated. We utilized a self-developed questionnaire which has been successfully used before to measure patients’ knowledge about the ISM. Above that we aimed to evaluate potential associations between sociodemographic, medical, donation-specific, and psychosocial variables including adherence, levels of depression and anxiety, perceived social support, and cognitive functioning with the knowledge level.Results: The mean age of the patients was 52.4 years, 58.1% were men, and 66.6% were living in a partnership. The mean time since transplantation was 65.1 months. On average, patients answered 70.9% of the questions correctly. The percentage of correct answers per question differed considerably (54%– 92%). In univariate analyses, knowledge levels were positively associated with female gender, current partnership, German as first language and better cognitive functioning. However, the effect sizes were small.Conclusion: Taking into account that the patients after KTx can be expected to answer all questions correctly as they aim at basic knowledge, an average result of 70.9% corresponds to a moderate knowledge level. Consequently, the current educational approaches do not seem to be sufficient to inform all patients adequately. Further research is necessary on how to improve health knowledge in the long term.Keywords: health literacy, kidney transplantation, renal transplantation, adherence, immunosuppressive medication

Arno Kerling,1 Dagmar Hartung,2 Brendon Stubbs,3,4 Momme Kück,1 Uwe Tegtbur,1 Lena Grams,1 Thomas Sanjay Weber-Spickschen,1 Kai G Kahl5 1Institute of Sport Medicine, Hannover Medical School, Hannover, Germany; 2Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany; 3Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, UK; 4Health Service and Population Research Department, Institute of Psychiatry, King’s College London, London, UK; 5Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany Objective: Sarcopenia leads to physical function impairment and at least to increasing all-cause mortality. There are notes on reduced muscle mass in patients with major depressive disorder (MDD). Whether an exercise intervention counteracts low muscle mass in patients with MDD has not been studied so far. Therefore, our study aimed at examining effects of regular aerobic exercise training on muscle mass in patients with MDD. Participants and methods: Thirty inpatients with MDD were included in the study, of which 20 received an additional supervised exercise program. Ten patients obtained treatment as usual. Muscle mass was measured using MRI before and 6 weeks after the training period (3 times per week for 45 minutes). Results: We found a significant effect of the exercise intervention on the amount of muscle mass depending on age, body mass index, and the physical activity score (P=0.042). Conclusion: Among other positive effects, regular exercise increases muscle mass in patients with MDD and, therefore, should be recommended as an additional treatment tool. Keywords: muscle mass, depression, sarcopenia, aerobic exercise

Arno Kerling,1 Gisela Stoltenburg-Didinger,2 Lena Grams,1 Uwe Tegtbur,1 Hauke Horstmann,1 Momme Kück,1 Holger Mellerowicz3 1Institute of Sports Medicine, Hannover Medical School, Hannover, Germany; 2Gisela Stoltenburg-Didinger, Institute of Cell and Neurobiology, Charité Universitätsmedizin Berlin CCO, Berlin, Germany; 3Holger Mellerowicz, Clinic for Pediatric Orthopedics and Traumatology, Helios Klinikum Emil von Behring, Berlin, Germany Purpose: Congenital clubfoot is one of the most common limb disorders in humans and its etiology is still unclear. In order to better understand the pathogenesis of patients with primary clubfoot, we examined whether there are quantitative changes in the extracellular matrix (ECM; based on common interstitial collagens [C] like CI and CIII, microfilamentous collagens like CVI, noncollagenous proteins like undulin, and enzymes like matrixmetalloproteinase [MMP]-2 and tissue inhibitor of matrixmetalloproteinase [TIMP]-2 that are known to play a role in fibrogenesis and fibrolysis) of muscles involved in the foot deformity of patients with primary clubfoot corresponding to fibrosis. Patients and methods: Thirty patients (age ranging from 4 months to 5 years and 7 months) with primary clubfoot were examined (23 male and 7 female patients), among whom 18 patients were affected on one side and 12 affected on both sides. Twenty-five biopsies were taken during the first operative foot correction (Crawford–McKay) and 5 in the context of relapses. Muscle biopsies were taken from the muscles involved in the defect (Musculus [M.] gastrocnemius and M. tibialis anterior) and from the M. vastus lateralis of the M. quadriceps femoris, which were treated as healthy comparison muscles. Quantitative analysis of the components of the ECM was performed using a computer-assisted fibrosis measurement of the immunohistochemically processed tissue samples. Results: We found higher values for M. gastrocnemius for CI, CIII, CVI and undulin in comparison with M. vastus lateralis. However, values for TIMP-2 were reduced. We found no significant differences for the components of M. tibialis anterior and M. vastus lateralis. There were no quantitative differences between male and female or between patients affected on one side and both sides. In patients who underwent relapse surgery, CI, CIII, CVI, and undulin of the gastrocnemius were significantly higher, while TIMP-2 was significantly lower. Conclusion: In the present study, we found manifest fibrosis in gastrocnemius due to quantitative changes in the ECM. In contrast to other studies, we found increasing fibrosis not just in contracted tissues but also in the muscle itself. Further studies are needed to clarify whether these changes are primarily responsible for the malfunction or whether they occur secondarily in the consequence of the dysfunction. Keywords: pes equinovarus, clubfoot, extracellular matrix, fibrosis, collagens, TIMP-2

Olaf Holz,1,* Stefan Roepcke,2,* Henrik Watz,3 Uwe Tegtbur,4 Gezim Lahu,2 Jens M Hohlfeld1 1Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), German Center for Lung Research (DZL, BREATH), Hannover, Germany; 2Takeda Pharmaceuticals International GmbH, Glattpark-Opfikon, Switzerland; 3Pulmonary Research Institute at Lung Clinic Grosshansdorf, German Center for Lung Research (DZL, ARCN), Grosshansdorf, 4Institute for Sports Medicine, Hannover Medical School (MHH), Hannover, Germany *These authors contributed equally to this work Abstract: There is an ongoing demand for easily accessible biomarkers related to pathophysiological processes in chronic obstructive pulmonary disease (COPD). Short-term intense exercise is known to increase the peripheral blood levels of cytokines. Therefore, we tested the potential and the repeatability of an exercise challenge to amplify seven serum biomarkers (interleukin 6 [IL6], C-reactive protein [CRP], myeloperoxidase [MPO], leukotriene B4, soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, and von Willebrand factor [VWF]) in smokers with and without COPD. Twenty-three smokers with moderate COPD (GOLD 2) and 23 sex- and age-matched healthy smokers underwent up to 30-minute submaximal, constant-load exercise (75% of maximum work load) on two occasions separated by 4 weeks (second challenge n=19/20). Serum samples were obtained before, 5 minutes after the start, at the end of exercise (maximum 30 minutes or until exhaustion), and after additional 20 minutes of rest. The median (interquartile range) exercise time until exhaustion in the two challenges was 10.0 (4.0) minutes and 10.0 (8.0) minutes in smokers with COPD and 22.0 (16.0) minutes and 26.5 (14.5) minutes in healthy smokers. The exercise challenge significantly increased the serum concentrations of IL6 and VWF, but decreased the concentrations of MPO. Healthy smokers showed a significantly greater increase (at the end of exercise compared to before exercise) in IL6 (P=0.01) and a larger decline (P=0.03) in MPO. The overall profile of the serum markers during the exercise challenge was shown to be repeatable in the second challenge. In summary, intense load exercise is capable of changing the concentration of inflammatory and endothelial function markers. Especially, the decline in the level of MPO, a marker closely related to cardiovascular risk, appears to be of clinical interest, as the exercise-induced decline might be related to the beneficial effects of physical activity in general. Keywords: serum biomarker, systemic inflammation, physical activity