(1) Background: Insulin resistance (IR) is a characteristic pathophysiologic feature in heart failure (HF). We tested the hypothesis that skeletal muscle metabolism is differently impaired in patients with reduced (HFrEF) vs. preserved (HFpEF) ejection fraction.

(2) Methods: carbohydrate and lipid metabolism was studied in situ by intramuscular microdialysis in patients with HFrEF (59 +/- 14y, NYHA I-III) and HFpEF (65 +/- 10y, NYHA I-II) vs. healthy subjects of similar age during the oral glucose load (oGL);

(3) Results: There were no difference in fasting serum and interstitial parameters between the groups. Blood and dialysate glucose increased significantly in HFpEF vs. HFrEF and controls upon oGT (both p < 0.0001), while insulin increased significantly in HFrEF vs. HFpEF and controls (p < 0.0005). Muscle tissue perfusion tended to be lower in HFrEF vs. HFpEF and controls after the oGL (p = 0.057). There were no differences in postprandial increases in dialysate lactate and pyruvate. Postprandial dialysate glycerol was higher in HFpEF vs. HFrEF and controls upon oGL (p = 0.0016);

(4) Conclusion: A pattern of muscle glucose metabolism is distinctly different in patients with HFrEF vs. HFpEF. While postprandial IR was characterized by impaired tissue perfusion and higher compensatory insulin secretion in HFrEF, reduced muscle glucose uptake and a blunted antilipolytic effect of insulin were found in HFpEF.

The gut microbiome plays a major role in human health, and gut microbial imbalance or dysbiosis is associated with disease development. Modulation in the gut microbiome can be used to treat or prevent different diseases. Gut dysbiosis increases with aging, and it has been associated with the impairment of gut barrier function leading to the leakage of harmful metabolites such as trimethylamine (TMA). TMA is a gut metabolite resulting from dietary amines that originate from animal-based foods. TMA enters the portal circulation and is oxidized by the hepatic enzyme into trimethylamine oxide (TMAO). Increased TMAO levels have been reported in elderly people. High TMAO levels are linked to peripheral artery disease (PAD), endothelial senescence, and vascular aging. Emerging evidence showed the beneficial role of probiotics and prebiotics in the management of several atherogenic risk factors through the remodeling of the gut microbiota, thus leading to a reduction in TMAO levels and atherosclerotic lesions. Despite the promising outcomes in different studies, the definite mechanisms of gut dysbiosis and microbiota-derived TMAO involved in atherosclerosis remain not fully understood. More studies are still required to focus on the molecular mechanisms and precise treatments targeting gut microbiota and leading to atheroprotective effects.

The energy homeostasis of the organism is orchestrated by a complex interplay of energy substrate shuttling, breakdown, storage, and distribution. Many of these processes are interconnected via the liver. Thyroid hormones (TH) are well known to provide signals for the regulation of energy homeostasis through direct gene regulation via their nuclear receptors acting as transcription factors. In this comprehensive review, we summarize the effects of nutritional intervention like fasting and diets on the TH system. In parallel, we detail direct effects of TH in liver metabolic pathways with regards to glucose, lipid, and cholesterol metabolism. This overview on hepatic effects of TH provides the basis for understanding the complex regulatory network and its translational potential with regards to currently discussed treatment options of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) involving TH mimetics.

Colorectal cancer (CRC) is the third most prevalent and second deadliest cancer worldwide. In addition, metastasis directly causes up to 90% of all CRC deaths, highlighting the metastatic burden of the disease. Biomarkers such as S100A4 and MACC1 aid in identifying patients with a high risk of metastasis formation. High expression of S100A4 or MACC1 and to a greater extent the combination of both biomarkers is a predictor for metastasis and poor patient survival in CRC. MACC1 is a tumor-initiating and metastasis-promoting oncogene, whereas S100A4 has not been shown to initiate tumor formation but can, nevertheless, promote malignant tumor growth and metastasis formation. Cantharidin is a natural drug extracted from various blister beetle species, and its demethylated analogue norcantharidin has been shown in several studies to have an anti-cancer and anti-metastatic effect in different cancer entities such as CRC, breast cancer, and lung cancer. The impact of the natural compound cantharidin and norcantharidin on S100A4 and MACC1 gene expression, cancer cell migration, motility, and colony formation in vitro was tested. Here, for the first time, we have demonstrated that cantharidin and norcantharidin are transcriptional inhibitors of S100A4 and MACC1 mRNA expression, protein expression, and motility in CRC cells. Our results clearly indicate that cantharidin and, to a lesser extent, its analogue norcantharidin are promising compounds for efficient anti-metastatic therapy targeting the metastasis-inducing genes S100A4 and MACC1 for personalized medicine for cancer patients.

LMNA-related muscular dystrophy is an autosomal-dominant progressive disorder caused by mutations in LMNA. LMNA missense mutations are becoming correctable with CRISPR/Cas9-derived tools. Evaluating the functional recovery of LMNA after gene editing bears challenges as there is no reported direct loss of function of lamin A/C proteins in patient-derived cells. The proteins encoded by LMNA are lamins A/C, important ubiquitous nuclear envelope proteins but absent in pluripotent stem cells. We induced lamin A/C expression in induced pluripotent stem cells (iPSCs) of two patients with LMNA-related muscular dystrophy, NM_170707.4 (LMNA): c.1366A > G, p.(Asn456Asp) and c.1494G > T, p.(Trp498Cys), using a short three-day, serum-induced differentiation protocol and analyzed expression profiles of co-regulated genes, examples being COL1A2 and S100A6. We then performed precise gene editing of LMNA c.1366A > G using the near-PAMless (PAM: protospacer-adjacent motif) cytosine base editor. We show that the mutation can be repaired to 100% efficiency in individual iPSC clones. The fast differentiation protocol provided a functional readout and demonstrated increased lamin A/C expression as well as normalized expression of co-regulated genes. Collectively, our findings demonstrate the power of CRISPR/Cas9-mediated gene correction and effective outcome measures in a disease with, so far, little perspective on therapies.

Critical illness myopathy (CIM) is an acquired, devastating, multifactorial muscle-wasting disease with incomplete recovery. The impact on hospital costs and permanent loss of quality of life is enormous. Incomplete recovery might imply that the function of muscle stem cells (MuSC) is impaired. We tested whether epigenetic alterations could be in part responsible. We characterized human muscle stem cells (MuSC) isolated from early CIM and analyzed epigenetic alterations (CIM n = 15, controls n = 21) by RNA-Seq, immunofluorescence, analysis of DNA repair, and ATAC-Seq. CIM-MuSC were transplanted into immunodeficient NOG mice to assess their regenerative potential. CIM-MuSC exhibited significant growth deficits, reduced ability to differentiate into myotubes, and impaired DNA repair. The chromatin structure was damaged, as characterized by alterations in mRNA of histone 1, depletion or dislocation of core proteins of nucleosome remodeling and deacetylase complex, and loosening of multiple nucleosome-spanning sites. Functionally, CIM-MuSC had a defect in building new muscle fibers. Further, MuSC obtained from the electrically stimulated muscle of CIM patients was very similar to control MuSC, indicating the impact of muscle contraction in the onset of CIM. CIM not only affects working skeletal muscle but has a lasting and severe epigenetic impact on MuSC.

Chemokines or chemotactic cytokines play a pivotal role in the immune pathogenesis of liver cirrhosis and hepatocellular carcinoma (HCC). Nevertheless, comprehensive cytokine profiling data across different etiologies of liver diseases are lacking. Chemokines might serve as diagnostic and prognostic biomarkers. In our study, we analyzed serum concentrations of 12 inflammation-related chemokines in a cohort of patients (n = 222) with cirrhosis of different etiologies and/or HCC. We compared 97 patients with cirrhosis and treatment-naive HCC to the chemokine profile of 125 patients with cirrhosis but confirmed absence of HCC. Nine out of twelve chemokines were significantly elevated in sera of cirrhotic patients with HCC compared to HCC-free cirrhosis controls (CCL2, CCL11, CCL17, CCL20, CXCL1, CXCL5, CXCL9, CXCL10, CXCL11). Among those, CXCL5, CXCL9, CXCL10, and CXCL11 were significantly elevated in patients with early HCC according to the Barcelona Clinic Liver Cancer (BCLC) stages 0/A compared to cirrhotic controls without HCC. In patients with HCC, CXCL5 serum levels were associated with tumor progression, and levels of CCL20 and CXCL8 with macrovascular invasion. Importantly, our study identified CXCL5, CXCL9, and CXCL10 as universal HCC markers, independent from underlying etiology of cirrhosis. In conclusion, regardless of the underlying liver disease, patients with cirrhosis share an HCC-specific chemokine profile. CXCL5 may serve as a diagnostic biomarker in cirrhotic patients for early HCC detection as well as for tumor progression.

Immune checkpoint therapy (ICT) has shown promising potential in the treatment of multiple solid tumors. However, the role of ICT in pancreatic ductal adenocarcinoma (PDAC) remains limited. Patterns of immune checkpoints (ICs) in PDAC represent the basis for establishing a potent ICT. The aim of this study is to create a profile of IC expression and its prognostic relevance in cancer cells of PDAC. Therefore, tumor cells from peripheral and central tissue microarray (TMA) spots from histologically confirmed PDAC of 68 patients after tumor resection were investigated in terms of expressions of TIM3, IDO, B7H4, LAG3, VISTA, and PD-L1 using immunohistochemistry. The presence of the respective ICs was compared to overall survival (OS). The presence of VISTA and PD-L1 significantly correlates with shorter OS (median OS: 22 months vs. 7 months and 22 months vs. 11 months, respectively, p < 0.05). For the presence of TIM3, IDO, B7H4, and LAG3, no difference in OS was observed (p > 0.05). The analysis of OS of combined subgroups for VISTA and PD-L1 (VISTA and PD-L1 neg., VISTA pos. and PD-L1 neg., VISTA neg. and PD-L1 pos., and VISTA and PD-L1 pos.) yielded overall statistical significance difference (p = 0.02). These results suggest that the presence of VISTA and PD-L1 is of prognostic relevance and potentially qualifies them as targets for ICT.

Targeting of MAP kinase pathways by BRAF inhibitors has evolved as a key therapy for BRAF-mutated melanoma. However, it cannot be applied for BRAF-WT melanoma, and also, in BRAF-mutated melanoma, tumor relapse often follows after an initial phase of tumor regression. Inhibition of MAP kinase pathways downstream at ERK1/2, or inhibitors of antiapoptotic Bcl-2 proteins, such as Mcl-1, may serve as alternative strategies. As shown here, the BRAF inhibitor vemurafenib and the ERK inhibitor SCH772984 showed only limited efficacy in melanoma cell lines, when applied alone. However, in combination with the Mcl-1 inhibitor S63845, the effects of vemurafenib were strongly enhanced in BRAF-mutated cell lines, and the effects of SCH772984 were enhanced in both BRAF-mutated and BRAF-WT cells. This resulted in up to 90% loss of cell viability and cell proliferation, as well as in induction of apoptosis in up to 60% of cells. The combination of SCH772984/S63845 resulted in caspase activation, processing of poly (ADP-ribose) polymerase (PARP), phosphorylation of histone H2AX, loss of mitochondrial membrane potential, and cytochrome c release. Proving the critical role of caspases, a pan-caspase inhibitor suppressed apoptosis induction, as well as loss of cell viability. As concerning Bcl-2 family proteins, SCH772984 enhanced expression of the proapoptotic Bim and Puma, as well as decreased phosphorylation of Bad. The combination finally resulted in downregulation of antiapoptotic Bcl-2 and enhanced expression of the proapoptotic Noxa. In conclusion, combined inhibition of ERK and Mcl-1 revealed an impressive efficacy both in BRAF-mutated and WT melanoma cells, and may thus represent a new strategy for overcoming drug resistance.

Background: For optimal recommendations in cardiovascular training for the general population, knowing the essential parameters for physical fitness is required. Heart rate recovery (HRR) is an easy-to-measure parameter and is discussed to derive the physical fitness of an individual subject. This study evaluates HRR as a potential physical fitness parameter for public health programs, as it is measured in every ergometry.

Methods: In this retrospective cross-sectional study, we analyzed HRR regarding physical fitness (W/kg (IAT: individual anaerobic threshold)). In total, we analyzed 1234 performance protocols in cycle ergometry. Significance tests (p < 0.001) and multiple linear regression were performed.

Results: The analysis of HRR and weight-related performance showed a significant correlation with a moderate coefficient of determination (R-2 = 0.250). The coefficient of determination increases from very weak correlation levels at 1 min post-workout towards weak to moderate levels of correlation at 5 min post-workout.

Conclusions: In this study HRR and the weight-related performance at the IAT showed a significant correlation with a mean strength. Thus, a prediction or conclusion on physical performance based singularly on HRR decrease is not recommended. However, in preventive medicine, HRR should be measured and observed on a long-term basis, for analysis of vagal activity and to draw to inferences of mortality.

Background: Active exercise therapy plays an essential role in tackling the global burden of obesity. Optimizing recommendations in individual training therapy requires that the essential parameters heart rate HR(IAT) and work load (W/kg(IAT) at individual anaerobic threshold (IAT) are known. Performance diagnostics with blood lactate is one of the most established methods for these kinds of diagnostics, yet it is also time consuming and expensive.

Methods: To establish a regression model which allows HR(IAT) and (W/kg(IAT) to be predicted without measuring blood lactate, a total of 1234 performance protocols with blood lactate in cycle ergometry were analyzed. Multiple linear regression analyses were performed to predict the essential parameters (HR(IAT)) (W/kg(IAT)) by using routine parameters for ergometry without blood lactate.

Results: HR(IAT) can be predicted with an RMSE of 8.77 bpm (p < 0.001), R2 = 0.799 (|R| = 0.798) without performing blood lactate diagnostics during cycle ergometry. In addition, it is possible to predict W/kg(IAT) with an RMSE (root mean square error) of 0.241 W/kg (p < 0.001), R2 = 0.897 (|R| = 0.897).

Conclusions: It is possible to predict essential parameters for training management without measuring blood lactate. This model can easily be used in preventive medicine and results in an inexpensive yet better training management of the general population, which is essential for public health.

Chronic back pain has a high prevalence, especially in older adults, and seriously affects sufferers' quality of life. Segmental stabilization exercise (SSE) is often used during physiotherapy to enhance core stability. The execution of SSE requires the selective contraction of deep abdominal and back muscles. Motor learning can be supported using ultrasound imaging as visual biofeedback. ULTRAWEAR is a mobile ultrasound system that provides deep learning-based biofeedback on SSE execution, which is currently under development. We interviewed 15 older chronic back pain patients (CBPPs) to investigate their pain management behavior, experience with SSE, as well as their needs and requirements for ULTRAWEAR. We also gathered information about future-usage scenarios. CBPPs reported a high willingness to use the system as a feedback tool both in physiotherapeutic practices and at home. The automated detection and evaluation of muscle contraction states was highlighted as a major benefit of the system compared to the more subjective feedback provided by traditional methods such as palpation. The system to be developed was perceived as a helpful solution to support learning about SSE.

In times of social and ecological crises, such as COVID-19 with lockdowns and implementing the impact of climate change, mental health degrades. Being outdoors in nature can be health-promoting, can decrease depression, and increase mental well-being. This pilot study investigated the relationships between nature-based therapy, mental health, and individuals' connectedness to nature. We hypothesize that nature-based therapy has a positive impact on individual mental health and connectedness to nature. A mixed-method approach was used to evaluate the effectiveness of nature-based therapy for young psychosomatic patients. The results demonstrated improvements in mental well-being and connectedness to nature through therapy. Additionally, depression scores decreased. Patients reported the importance of the therapist setting the space, the supportive environment, the poems that fostered the nature connection, improvement at the soul level, and overall doing something meaningful. Every patient experienced nature-based therapy as effective. To conclude, the study gives a first insight into the processes of nature-based therapy in the German population at work and the effectiveness of nature-based therapy. Further questions, e.g., season effects, longitudinal effects, and whether patients with low connectedness to nature gain more out of the intervention remain unanswered.

Background: Excessive alcohol consumption is a major public health problem, with substance use early in life contributing to higher levels of use later in life. Virtual reality (VR) is an innovative technology for alcohol prevention among adolescents that could solve the problem of insufficient outreach to the target group of young people. The co-created German Virtual LimitLab simulation is one of the few examples of VR-based alcohol prevention tools and consists of a virtual house party simulation. The aims of Virtual LimitLab are to increase the users' awareness of how social pressure can influence their own decision-making as well as to enable various actions and communication strategies in order to train competencies when dealing with alcohol. The present study thus aims to explore adolescents' content- and technique-specific perceptions of Virtual LimitLab in order to gain insights into user experiences and to test the prototype with the German target group.

Methods: Four semi-structured focus groups with adolescents aged 15-18 years (n = 13) were conducted and analyzed using thematic analyses. A user experience questionnaire (UEQ-S) was applied in order to quantitatively assess adolescents' satisfaction with Virtual LimitLab.

Results: Three main themes were identified (VR experience, content, and technical aspects). Participants positively assessed both the content and the technical aspects of Virtual LimitLab. This trend was also seen by the UEQ-S data, which yielded positive ratings for both pragmatic and hedonic quality. The broad variety of options in the simulation that allow the user to try new behaviors was perceived particularly positively. In general, Virtual LimitLab was regarded as an innovative tool that encourages adolescents to think critically about their personal alcohol consumption. Technical errors in the simulation and users' difficulties in identifying with the simulation were the main points of criticism.

Conclusions: Feedback from adolescent users revealed positive and therefore promising results when using Virtual LimitLab as a gaming alcohol-prevention tool. Some technical aspects still need to be improved in order to further refine the prototype, and suggestions for expanding the content of the application have already been made.

Introduction: People experiencing homelessness face lower life expectancy, higher prevalence of somatic and mental diseases and a more difficult access to healthcare compared to people in secure living. During the COVID-19 pandemic transmission rates were higher among people experiencing homelessness and preventive public health measures were not properly adapted to the specific needs of people experiencing homelessness. Thus, goal of our study was understanding the determinants of acceptability and access of the COVID-19 vaccine.

Materials and methods: We conducted a qualitative interview study with twenty guideline interviews with adult people currently experiencing homelessness in Berlin, Germany (August 2021 - April 2022). Participants were approached in a purposive sampling strategy. The interviews were analyzed with qualitative content analysis according to Mayring.

Results: Acceptance and attitude toward the COVID-19 vaccine is influenced by confidence in the vaccine as well as in the political and healthcare system, the individual COVID-19 risk perception and sense of collective responsibility. Overall, the acceptance of the vaccine was high among our participants. Facilities offering low threshold COVID-19 vaccines for people experiencing homelessness were perceived as helpful. Language barriers and the need for identity documents were major barriers to access the COVID 19 vaccine.

Discussion: People experiencing homelessness are a marginalized and vulnerable group often underrepresented in the public and scientific discourse. During the COVID-19 pandemic, preventive public health measures, including the COVID-19 vaccine, failed to consider specific needs of people experiencing homelessness. Multidimensional strategy to enhance inclusive healthcare are needed to improve access and to reduce discrimination and stigmatization.

Introduction: Psychotic-like experiences (PLEs) may occur due to changes in weighting prior beliefs and new evidence in the belief updating process. It is still unclear whether the acquisition or integration of stable beliefs is altered, and whether such alteration depends on the level of environmental and belief precision, which reflects the associated uncertainty. This motivated us to investigate uncertainty-related dynamics of belief updating in relation to PLEs using an online study design.

Methods: We selected a sample (n = 300) of participants who performed a belief updating task with sudden change points and provided self-report questionnaires for PLEs. The task required participants to observe bags dropping from a hidden helicopter, infer its position, and dynamically update their belief about the helicopter's position. Participants could optimize performance by adjusting learning rates according to inferred belief uncertainty (inverse prior precision) and the probability of environmental change points. We used a normative learning model to examine the relationship between adherence to specific model parameters and PLEs.

Results: PLEs were linked to lower accuracy in tracking the outcome (helicopter location) (beta = 0.26 +/- 0.11, p = 0.018) and to a smaller increase of belief precision across observations after a change point (beta = -0.003 +/- 0.0007, p < 0.001). PLEs were related to slower belief updating when participants encountered large prediction errors (beta = -0.03 +/- 0.009, p = 0.001). Computational modeling suggested that PLEs were associated with reduced overall belief updating in response to prediction errors (beta(PE) = -1.00 +/- 0.45, p = 0.028) and reduced modulation of updating at inferred environmental change points (beta(CPP) = -0.84 +/- 0.38, p = 0.023).

Discussion: We conclude that PLEs are associated with altered dynamics of belief updating. These findings support the idea that the process of balancing prior belief and new evidence, as a function of environmental uncertainty, is altered in PLEs, which may contribute to the development of delusions. Specifically, slower learning after large prediction errors in people with high PLEs may result in rigid beliefs. Disregarding environmental change points may limit the flexibility to establish new beliefs in the face of contradictory evidence. The present study fosters a deeper understanding of inferential belief updating mechanisms underlying PLEs.

Background: Research exploring the effects of yoga therapy (YT) on individuals with schizophrenia spectrum disorders (SSD) is scarce. Therefore, the current study aimed to explore possible mechanisms of actions and processes, as well as adverse effects of a novel yoga-based group intervention (YoGI) for in-patients with SSD in a German university hospital setting.

Material and methods: A longitudinal qualitative study was integrated into a rater-blinded randomized controlled trial, exploring the impact of a 4-week YoGI as add-on treatment. In-depth interviews were conducted with participants receiving YoGI (n = 19) in addition to treatment as usual (TAU) and a control group (n = 14) which only received TAU. Interviews were conducted at baseline (n = 33) and 4 weeks post-intervention (N = 28) to assess the participant's experiences and how they changed over time. The interviews (N = 61) were audio-taped, translated, coded, and analyzed by means of inductive thematic analysis. Separate case summaries were prepared for each participant to analyze longitudinal changes within subjects. The research team members collaboratively discussed the final list of themes and subcodes. Rater-based questionnaires, such as the Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), and Personal and Social Performance Scale (PSP) were administered at baseline to assess clinical outcomes.

Results: At baseline, participants reported a desire to improve their stress- and symptom management. A minority of participants expressed reservations toward yoga, and several psychosocial barriers were named, including worries about symptom exacerbation. At post-intervention, four mechanisms of change became evident from the interviews: (1) acquiring competence in relaxation, (2) increased interoceptive awareness, (3) feeling connected, and (4) a sense of spiritual wellbeing. A small number of participants reported difficulties with YoGI.

Conclusion: Generally, YoGI positively influenced participants' experiences of their inpatient stay, regarding distress, self- and body awareness, social connectedness, and spiritual wellbeing. However, participants also illuminated necessary adjustments to improve the intervention. YoGI will therefore be adapted and further developed in an iterative process based on a participant involvement approach. The efficacy regarding outcomes and processes needs to be investigated in a future larger-scaled randomized controlled trial.

The mandible (lower jaw) bone is aesthetically responsible for shaping the lower face, physiologically in charge of the masticatory movements, and phonetically accountable for the articulation of different phonemes. Thus, pathologies that result in great damage to the mandible severely impact the lives of patients. Mandibular reconstruction techniques are mainly based on the use of flaps, most notably free vascularized fibula flaps. However, the mandible is a craniofacial bone with unique characteristics. Its morphogenesis, morphology, physiology, biomechanics, genetic profile, and osteoimmune environment are different from any other non-craniofacial bone. This fact is especially important to consider during mandibular reconstruction, as all these differences result in unique clinical traits of the mandible that can impact the results of jaw reconstructions. Furthermore, overall changes in the mandible and the flap post-reconstruction may be dissimilar, and the replacement process of the bone graft tissue during healing can take years, which in some cases can result in postsurgical complications. Therefore, the present review highlights the uniqueness of the jaw and how this factor can influence the outcome of its reconstruction while using an exemplary clinical case of pseudoarthrosis in a free vascularized fibula flap.

Objective: In the field of non-treatable muscular dystrophies, promising new gene and cell therapies are being developed and are entering clinical trials. Objective assessment of therapeutic effects on motor function is mandatory for economical and ethical reasons. Main shortcomings of existing measurements are discontinuous data collection in artificial settings as well as a major focus on walking, neglecting the importance of hand and arm movements for patients' independence. We aimed to create a digital tool to measure muscle function with an emphasis on upper limb motility.

Methods: suMus provides a custom-made App running on smartwatches. Movement data are sent to the backend of a suMus web-based platform, from which they can be extracted as CSV data. Fifty patients with neuromuscular diseases assessed the pool of suMus activities in a first orientation phase. suMus performance was hence validated in four upper extremity exercises based on the feedback of the orientation phase. We monitored the arm metrics in a cohort of healthy volunteers using the suMus application, while completing each exercise at low frequency in a metabolic chamber. Collected movement data encompassed average acceleration, rotation rate as well as activity counts. Spearman rank tests correlated movement data with energy expenditure from the metabolic chamber.

Results: Our novel application "suMus, " sum of muscle activity, collects muscle movement data plus Patient-Related-Outcome-Measures, sends real-time feedback to patients and caregivers and provides, while ensuring data protection, a long-term follow-up of disease course. The application was well received from the patients during the orientation phase. In our pilot study, energy expenditure did not differ between overnight fasted and non-fasted participants. Acceleration ranged from 1.7 & PLUSMN; 0.7 to 3.2 +/- 0.5 m/sec(2) with rotation rates between 0.9 & PLUSMN; 0.5 and 2.0 & PLUSMN; 3.4 rad/sec. Acceleration and rotation rate as well as derived activity counts correlated with energy expenditure values measured in the metabolic chamber for one exercise (r = 0.58, p < 0.03).Conclusion: In the analysis of slow frequency movements of upper extremities, the integration of the suMus application with smartwatch sensors characterized motion parameters, thus supporting a use in clinical trial outcome measures. Alternative methodologies need to complement indirect calorimetry in validating accelerometer-derived energy expenditure data.