Articoli di riviste sul tema "Cologne (Germany). S. Andreastift"

Background: Although there have been no reported cardiac arrests in space to date, the risk of severe medical events occurring during long-duration spaceflights is a major concern. These critical events can endanger both the crew as well as the mission and include cardiac arrest, which would require cardiopulmonary resuscitation (CPR). Thus far, five methods to perform CPR in microgravity have been proposed. However, each method seems insufficient to some extent and not applicable at all locations in a spacecraft. The aim of the present study is to describe and gather data for two new CPR methods in microgravity. Materials and Methods: A randomized, controlled trial (RCT) compared two new methods for CPR in a free-floating underwater setting. Paramedics performed chest compressions on a manikin (Ambu Man, Ambu, Germany) using two new methods for a free-floating position in a parallel-group design. The first method (Schmitz–Hinkelbein method) is similar to conventional CPR on earth, with the patient in a supine position lying on the operator’s knees for stabilization. The second method (Cologne method) is similar to the first, but chest compressions are conducted with one elbow while the other hand stabilizes the head. The main outcome parameters included the total number of chest compressions (n) during 1 min of CPR (compression rate), the rate of correct chest compressions (%), and no-flow time (s). The study was registered on clinicaltrials.gov (NCT04354883). Results: Fifteen volunteers (age 31.0 ± 8.8 years, height 180.3 ± 7.5 cm, and weight 84.1 ± 13.2 kg) participated in this study. Compared to the Cologne method, the Schmitz–Hinkelbein method showed superiority in compression rates (100.5 ± 14.4 compressions/min), correct compression depth (65 ± 23%), and overall high rates of correct thoracic release after compression (66% high, 20% moderate, and 13% low). The Cologne method showed correct depth rates (28 ± 27%) but was associated with a lower mean compression rate (73.9 ± 25.5/min) and with lower rates of correct thoracic release (20% high, 7% moderate, and 73% low). Conclusions: Both methods are feasible without any equipment and could enable immediate CPR during cardiac arrest in microgravity, even in a single-helper scenario. The Schmitz–Hinkelbein method appears superior and could allow the delivery of high-quality CPR immediately after cardiac arrest with sufficient quality.

Abstract Background Due to severe immunosuppression, patients undergoing allogeneic hematopoietic stem cell transplantation (aSCT) are at increased risk of infection and especially bloodstream infections (BSI) remain a major cause of death. Knowledge of the specific epidemiology of pathogens and resistances is of utmost importance to optimize antimicrobial treatment strategies. Methods Based on the Cologne Cohort of Neutropenic Patients (CoCoNut) database, we conducted a retrospective analysis of blood cultures collected within 100 days following transplantation of patients undergoing aSCT between January 2009 and December 2018 at the University Hospital of Cologne, Germany. Contamination of coagulase-negative Staphylococci (CoNS) isolates (single positive isolate within 5 days) was considered within the analysis. Results In total, 843 aSCT patients were available for analysis (484/843 [57%] male). The median age was 53 (interquartile range [IQR] 43–62) years, predominant underlying diseases were acute myeloid leukemia (47%, 397/843), lymphoma (14%, 117/843), and acute lymphoblastic leukemia (11%, 89/843). Median inpatient stay was 39 (IQR 34–50) days, while 67/843 (8%) patients died. Antibacterial prophylaxis was administered in 289/843 (34%) and antifungal prophylaxis in 738/843 (88%) patients. BSI was diagnosed in 233/843 (28%) patients. In total, 5,489 pairs of blood cultures were taken (median 4 per patient, IQR 2–8), while a pathogen could only be detected in 922/5,489 (17%). Most frequent pathogens were CoNS (259/922, 28%), Enterococcus spp. (219/922, 24%), E. coli (132/922, 14%), Klebsiella spp. (44/922, 5%), P. aeruginosa (39/922, 4%), S. aureus (37/922, 4%), and Candida spp. (42/922, 5%). Polymicrobial infection was detected in 58/922 (6%) cases. Within Enterococci isolates, 24/219 (11%) were VRE. None of the Klebsiella, but 9/132 (7%) of E. coli isolates were ESBL positive. In 4/37 (11%) cases S. aureus isolates were MRSA. Conclusion Patients in the early phase after aSCT are at high risk of BSI with a predominantly gram-positive spectrum. Empirical antimicrobial treatment must consider pathogen epidemiology and resistance patterns while waiting for blood culture results. Disclosures All authors: No reported disclosures.

It is not surprising that Henry Edward Manning had strong opinions about the Kulturkampf, Otto von Bismarcks effort in the early 1870’s to bring the Roman Catholic Church in Germany under the control of the State. As head of the Catholic Church in England, it appropriately fell to Manning to condemn what most British Catholics would have seen as the persecution of their Church in the new German Empire. Moreover, Manning knew personally the bishops involved in the conflict with Bismarck from their time together at the Vatican Council. Indeed, he was well acquainted with some of them who had played important rôles, either for or against, in the great controversies of the Council that led to the definition of Papal Infallibility. MiecisIaus Ledochowski, Archbishop of Gnesen and Posen, imprisoned and expelled from his see by the German government in 1874, had, together with Manning, been a prominent infallibilist. Paulus Melchers, Archbishop of Cologne, and leader of the German inopportunists, suffered the same penalty. The bishops of Breslau, Trier and Paderborn, all of whom had played significant rôles at the Council, the first two against, the latter for the definition, were either imprisoned, expelled, or both. Manning considered these men to have suffered for the cause of religious liberty, and could not understand the indifference of British politicians, especially of liberals like Gladstone, to their fate.

This paper outlines a research project which is being conducted in the edu¬cational context of an international Master program: In 2001, an interdisci¬plinary and cohort-based Master program entitled “International Manage¬ment and Intercultural Communication/GlobalMBA” was founded, which is currently offered by a four-university consortium that includes the follow¬ing: Technische Hochschule Köln (TH Köln), Cologne, Germany, the Fac¬ulty of Management at the University of Warsaw (UW), Poland, Dongbei University of Finance and Economics (DUFE) in Dalian, China, and the Coggin College of Business at the University of North Florida (UNF) in Jacksonville, USA. During the program´s 15-month duration, a multina¬tional cohort of 25-30 students recruited from each of the four universi¬ties studies together for one semester at each university. Much of the coursework and assignments as well as the final Master thesis are written in multinational groups of three to four students, thus requiring the students to permanently prove their teamwork skills. Besides, given the in-built mobility and multinational cohort-based structure of the program, the students are continuously exposed to a variety of different cultural experi¬ences and encounters. The program´s curriculum includes management-oriented courses as well as courses on the theory and practice of intercul¬tural communication. In one of these latter modules called Applied Inter¬cultural Communication, which is taught in every location and has a strong country-specific perspective, students are required to produce reflective dia¬ries describing their cultural experiences. The research project presented here started in 2013 and is based on a qualitative analysis of students´ diary entries written during a time span of 15 months as part of the course requirements for this particular module. The project is intended to serve two main purposes:

Abstract We previously identified the cause of low levels of von Willebrand factor (VWF) in the RIIIS/J mouse strain to be a regulatory mutation, Mvwf1, in an N-acetylgalactosaminyltransferase, B4galnt2 (previously designated Galgt2). Mvwf1 causes a tissue-specific switch in B4galnt2 expression from intestinal epithelium to vascular endothelium, resulting in aberrant glycosylation of VWF and accelerated clearance from circulation. We have identified thirteen Mvwf1 inbred mouse strains that share this remarkable tissue-specific switch and a common 97kb haplotype block, including a 30kb region of 2–3% sequence divergence that flanks Exon 1. An RIIIS/J BAC transgene containing the entire Mvwf1 haplotype block and B4galnt2 gene confers vascular gene expression, while C57BL6/J BAC transgenes spanning the homologous region confer “wild-type” vessel(−), intestine(+) gene expression, indicating that one or more tissue-specific regulatory elements sufficient to recapitulate the Mvwf1 tissue-specific switch lie within the genomic region covered by these BACs. A wild-derived recombinant Mvwf1 allele containing the 3′ half of the Mvwf1 haplotype block confers the vessel(−), intestine(+) B4galnt2 expression pattern, placing the regulatory mutation(s) responsible for the Mvwf1 switch well upstream of the proximal promoter region. Sequence analysis of DNA from wild-caught individual mice confirmed the presence of a highly conserved wild mouse Mvwf1 founder allele that likely pre-dates the development of the inbred mouse strains. PCR of genomic DNA from wild caught mice representing M. m. musculus, M. m. domesticus, M. m. castaneus, M. m. molossinus, M. spretus, M. hortulanis, and M. macedonicus revealed that the Mvwf1 allele is common in wild M. m. domesticus populations in North America, Europe, and Africa, with an allele frequency as high as 60% in French mice. Population samples of M. m. domesticus from Cologne, Germany and the Massif Central region of France drastically differ in the frequency of this allele (0% vs. 60%). A significant reduction in microsatellite variability at B4galnt2 in the French population, as measured by the lnRH statistic, suggests a recent, local shift in the frequency of Mvwf1, likely due to a recent change in selective pressure. Analysis of independently trapped wild mice from the Massif Central region of France confirmed that Mvwf1 confers vascular endothelial B4galnt2 expression and causes significantly lower VWF levels (5.5+2.0 vs. 13.3+2.3, p<1x10−7) in this population. These data support a B4Galnt2 allele-specific survival advantage in wild mice, leading us to speculate that a similar survival advantage could account for the high prevalence of VWD in human populations.

Abstract Germline mutation status of BRCA1/2 and other breast cancer predisposition genes as predictive and prognostic biomarker: Results of the GeparX study (GeparX-BRCA) Background: There is accumulating evidence that the RANK/RANKL signaling pathway plays a pivotal role in breast tumorigenesis, particularly in the development of BRCA1-mutated tumors. Targeting the RANK pathway has been shown to attenuate breast cancer (BC) proliferation in vitro and in vivo. Studies using bone modifying agents as adjuvant therapy showed reduced rates of bone metastases and improved BC survival, as well as prevention of treatment-induced skeletal events. The GeparX clinical trial assessed the use of denosumab in patients with primary BC as an adjunct to neoadjuvant chemotherapy for its ability to enhance pathological complete response (pCR) rate and improve outcome. The trial randomized 780 patients twice to a total of 4 treatment groups (to receive or not receive denosumab; to receive nab-paclitaxel 125 mg/m2 weekly for 12 weeks or days 1 and 8 every 3 weeks for 4 cycles, both followed by 4 cycles of epirubicin/cyclophosphamide, 90/600 mg/m2 every 2 weeks/every 3 weeks according to the investigator´s choice). Carboplatin was given in triple-negative breast cancer (TNBC), and trastuzumab biosimilar ABP980 plus pertuzumab was given in human epidermal growth factor-2-positive (HER2+) BC. Overall, the pCR (ypT0 ypN0) rate was 41% with denosumab vs 43% without; nab-paclitaxel at a dosage of 125 mg/m2 weekly resulted in a significantly higher pCR rate of 45% vs 39% with a dosage of 125 mg/m2 days 1 and 8 every 3 weeks. Research question: Does the germline mutation status of BRCA1/2 and other BC predisposition genes affect treatment outcome in the GeparX study? Methods: Genetic germline analyses assessing pathogenic variants in BRCA1/2 and 16 other BC predisposition genes were performed at the Center for Familial Breast and Ovarian Cancer, Cologne, Germany; 767 patients were included in this secondary investigation (308 TNBC, 306 HER2-/hormone receptor positive [HR+], 153 HER2+). Findings: Germline BRCA1/2 mutations were present in 91/767 patients (11.9%), with a higher mutation prevalence in TNBC (50/308, 16.2%) and HER2-/HR+ BC (37/306, 12.1%), and a low mutation prevalence in HER2+ BC (4/153, 2.6%). Overall, the pCR rate (ypT0 ypN0) was elevated in BRCA1/2 mutation carriers vs non-carriers (49.5% vs 41.1%, respectively; overall: OR 1.40, 95% CI 0.90-2.17; TNBC: OR 1.24, 95% CI 0.67-2.32; HER2-/HR+: OR 1.83, 95% CI 0.86-3.88). Highest pCR rates were observed in TNBC in BRCA1/2 mutation carriers vs non-carriers (60% vs. 54.7%, respectively). Highest pCR rate differences were observed HER2-/HR+ BC in BRCA1/2 mutation carriers vs non-carriers (32.4% vs. 20.8%, respectively). Regarding treatment arms, both BRCA1/2 mutation carriers and non-carriers benefitted most from nab-paclitaxel at a dosage of 125 mg/m2 weekly vs 125 mg/m2 days 1 and 8 every 3 weeks (BRCA1/2 mutation carriers: 55.3% vs 43.2%, respectively; OR 1.63, 95% CI 0.71-3.73; non-carriers: 43.7% vs 38.6%, respectively; OR 1.24, 95% CI 0.91-1.68). No beneficial effect was observed for denosumab vs no denosumab (51.1% vs 47.8% for BRCA1/2 mutation carriers, respectively; OR 1.14, 95% CI 0.50-2.60; 40.3% vs 41.9% for non-carriers, respectively; OR 0.94, 95% CI 0.69-1.27). Of the 617 BRCA1/2-negative patients, 59 patients carried mutations in other BC predisposition genes which did not predict therapy response compared to patients without any mutation. Conclusions: Irrespective of the treatment arm, higher pCR rates were observed in BRCA1/2 mutations carriers vs non-carriers. Both BRCA1/2 mutation carriers and non-carriers benefitted most from weekly nab-paclitaxel. No pronounced effect was observed for denosumab in either group. Key words: GeparX, denosumab, BRCA1/2 germline mutations, therapy response Funding: GeparX was financially supported by Amgen and BMS (Celgene). Citation Format: Rita K. Schmutzler, Theresa Link, Eric Hahnen, Mattea Reinisch, Jan Hauke, Marianne Just, Michael Untch, Corinna Ernst, Oliver Stötzer, Peter A. Fasching, Mohamad Kayali, Pauline Wimberger, Andreas Schneeweiss, Sandra Schmidt, Sabine Seiler, Christian Jackisch, Marc Thill, Kerstin Rhiem, Carsten Denkert, Valentina Nekljudova, Johannes Holtschmidt, Jens-Uwe Blohmer, Sibylle Loibl. Germline mutation status of BRCA1/2 and other breast cancer predisposition genes as predictive and prognostic biomarker: Results of the GeparX study (GeparX-BRCA) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-02-13.

Background/AimsTo analyse graft detachments prior to rebubbling, the influence of rebubbling on the postoperative outcome after Descemet membrane endothelial keratoplasty (DMEK) and the need for rebubbling on the contralateral eye.MethodsIn this retrospective cohort study, out of 1541 DMEKs, optical coherence tomography scans and clinical records of 499 eyes undergoing rebubbling after DMEK at the University Hospital of Cologne, Cologne, Germany, were examined. Main Outcome measures were (a) number, localisation and size of graft detachments; (b) influence of rebubbling/s on postoperative outcome after 12 months; and (c) rebubbling risk of the contralateral eye after DMEK.ResultsMean number of detachment areas was 2.02±0.9. Mean lateral diameter of all detachments was 4534.76±1920.83 μm. Mean axial diameter was 382.53±282.02 μm. Detachments were equally distributed over all regions of the cornea. Best spectacle corrected visual acuity ( BSCVA) after 12 months was 0.197±0.23 logarithm of the minimum angle of resolution, endothelial cell density (ECD) was 1575.21±397.71 cells/mm2 and mean central corneal thickness (CCT) was 566.37±68.11 μm. BSCVA, CCT, ECD or endothelial cell loss of all rebubbled patients were not influenced by the number of rebubblings or the time between DMEK and rebubbling. Of the rebubbled patients, which received a DMEK subsequently on the other eye, 193 (58.8%) also received a rebubbling, which was significantly higher, when compared to the overall rebubbling rate of 32.3% (p=0.000).ConclusionsThe overall number of rebubblings has no influence on the postoperative outcome after DMEK, if a rebubbling becomes necessary. Patients who received a rebubbling on one eye have an elevated risk for a rebubbling on the fellow eye.

We measure the willingness to compete of entrepreneurs and salaried workers in an experiment. Participants can choose between a piece rate and a tournament scheme in either private or public. We find that in the private condition, entrepreneurs are less competitive than salaried workers, but in the public condition, this ordering is reversed. Survey data suggest that perceived norms of appropriate behavior, along with beliefs about the instrumental value of competitiveness for professional success, can explain why entrepreneurs are more competitive when decisions are publicly observable. We also find that the latter condition improves the quality of experimental decisions. This paper was accepted by Yan Chen, behavioral economics and decision analysis. Funding: Financial support from the Deutsche Forschungsgemeinschaft (German Research Foundation) under Germany´s Excellence Strategy [Grant EXC 2126/1–390838866], the University of Cologne through the Hans Kelsen Prize and the Austrian Science Fund through the Special Research Area [Grant SFB F63] is gratefully acknowledged. Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2023.4838 .

Organ donation after brain death is constantly lower in Germany compared to other countries. Instead, representative surveys show a positive attitude towards donation. Why this does not translate into more donations remains questionable. We retrospectively analyzed all potential brain dead donors treated in the university hospitals of Aachen, Bielefeld, Bonn, Essen, Düsseldorf, Cologne and Münster between June 2020 and July 2021. 300 potential brain dead donors were identified. Donation was utilized in 69 cases (23%). Refused consent (n = 190), and failed utilization despite consent (n = 41) were reasons for a donation not realized. Consent was significantly higher in potential donors with a known attitude towards donation (n = 94) compared to a decision by family members (n = 195) (49% vs. 33%, p = 0.012). The potential donor´s age, status of interviewer, and the timing of the interview with decision-makers had no influence on consent rates, and it was comparable between hospitals. Refused consent was the predominant reason for a donation not utilized. Consent rate was lower than in surveys, only a known attitude towards donation had a significant positive influence. This indicates that survey results do not translate well into everyday clinical practice and promoting a previously documented decision on organ donation is important.

Today the total length of the federal trunk highway roads in Germany is about 50,000 km being one of the densest traffic in whole Europe. Among these are approximately 40,000 bridges with a total area of 30 million. Square meters. Fifty percent of these bridges were built in the years between 1960 to 1980. At that time these bridges were mainly designed according to German Standard DIN 1072 for bridge class SLW 60 (60 ton truck). Based on the traffic given at those times, no fatigue checks were required. This assumption seemed fair enough because the massive increase, especially in heavy traffic, could not have been anticipated. Since the mid-20th century until our days, the bridges over the river Rhine have set a milestone on the history of bridge engineering. Some contributions from the team led by Fritz Leonhardt and Wolfhart Andrä, such as the Cologne-Rodenkirchen suspension bridge, the series of steel bridges with continuous webs developed in the 60´s decade, the Düsseldorf cable stayed bridges family, the widenings and retrofitings of the 80´s decade, or the most recent contributions, encompass widely different typologies and periods and provide valuable learnings. Their preservation, retrofit or eventual replace if necessary, entail an important challenge for the present and future. The starting point of such a strengthening or eventual replacement is always the assessment of the existing bridge under consideration of its actual condition, the prognosticated loads and requirements of future utilization. This assessment process and rating of existing structures was regulated by the German government in 2012 in the “Nachrechnungs”- guidelines. The result of such an assessment is the basis of any further decision about the future of a structure, whether it will be rehabilitated, retrofitted or replaced. The presentation will focus on the experiences gained under the new guideline and the wide range of engineering services involved in such a rehabilitation planning, using the examples of the Suspension bridges over the River Rhine at Emmerich and Köln-Mühlheim, and will show the specific experience gained through these strengthening projects, but also a short overview about the new cable-stayed bridges in Leverkusen and Duisburg that are built under the premise to maintain traffic for 2 of the most importante highways in Germany.

During spaceflight, humans experience a variety of physiological changes due to deviations from familiar earth conditions. Specifically, the lack of gravity is responsible for many effects observed in returning astronauts. These impairments can include structural as well as functional changes of the brain and a decline in cognitive performance. However, the underlying physiological mechanisms remain elusive. Alterations in neuronal activity play a central role in mental disorders and altered neuronal transmission may also lead to diminished human performance in space. Thus, understanding the influence of altered gravity at the cellular and network level is of high importance. Previous electrophysiological experiments using patch clamp techniques and calcium indicators have shown that neuronal activity is influenced by altered gravity. By using multi-electrode array (MEA) technology, we advanced the electrophysiological investigation covering single-cell to network level responses during exposure to decreased (micro-) or increased (hyper-) gravity conditions. We continuously recorded in real-time the spontaneous activity of human induced pluripotent stem cell (hiPSC)-derived neural networks in vitro. The MEA device was integrated into a custom-built environmental chamber to expose the system with neuronal cultures to up to 6 g of hypergravity on the Short-Arm Human Centrifuge at the DLR Cologne, Germany. The flexibility of the experimental hardware set-up facilitated additional MEA electrophysiology experiments under 4.7 s of high-quality microgravity (10–6 to 10–5 g) in the Bremen drop tower, Germany. Hypergravity led to significant changes in activity. During the microgravity phase, the mean action potential frequency across the neural networks was significantly enhanced, whereas different subgroups of neurons showed distinct behaviors, such as increased or decreased firing activity. Our data clearly demonstrate that gravity as an environmental stimulus triggers changes in neuronal activity. Neuronal networks especially reacted to acute changes in mechanical loading (hypergravity) or de-loading (microgravity). The current study clearly shows the gravity-dependent response of neuronal networks endorsing the importance of further investigations of neuronal activity and its adaptive responses to micro- and hypergravity. Our approach provided the basis for the identification of responsible mechanisms and the development of countermeasures with potential implications on manned space missions.

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): National Research Agency (ANR) French Federation of Cardiology : “Aide à la recherche par équipe 2018, Cardiopathies de l’enfant” Introduction After percutaneous implantation of an atrial septal defect (ASD) occluder device, a complex healing process leads to the device coverage within several months. However, an unexplained incomplete device coverage is at risk of complications such as thrombosis or infectious endocarditis. Purpose The aim of the study was to assess the device coverage process of ASD occluder devices in a chronic sheep model using micro-CT technology. Methods After percutaneous creation of an ASD by catheterization, 8 ewes (mean age 5.4 ± 0.7 yo and mean weight 55.6 ± 7.9 kg) were implanted with a 16-mm Nit-Occlud ASD-R occluder (PFM medical, Cologne, Germany) and were followed for 1 month (N = 3) and 3 months (N =5). After heart explantation, a iodine contrast agent was used to enhance the tissue signal. The device coverage was then assessed by micro-CT and the results were compared to histology, used as the gold standard for healing evaluation. The micro-CT image resolution was 41.7 µm. Reconstruction was performed in 2D and 3D with Amira® software, allowing to obtain images that were exploited by a code to measure the surface for each disk of the analyzed devices. Histological study was performed after resin embedding and Richardson blue staining was used. The pathologist was blinded to the duration of animals’ follow-up and micro-CT results. Results ASD creation and device closure was successful in 100% animals without complications. Following heart explantation, macroscopic assessment of devices showed that the coverage was complete for the left-side disk regardless of the duration of the follow-up and variable for the right-side disk, depending of the protrusion of this disk. 2D and 3D micro-CT analysis allowed an accurate evaluation of device coverage of each disk and was overall well correlated to histology slices (cf Figure). Surface calculation from micro-CT images showed that the median surface of coverage was 93 ± 8% for the left-side disk and 55 ± 31% for the right-side disk. Conclusion This preliminary study made the proof of concept that micro-CT is a reliable tool to assess the coverage of intra-cardiac occluders in vitro. The translation to clinical practice is challenging but would allow an individual follow-up, to avoid thrombotic or infective complications. Abstract Figure.

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Translational Medicine and Exercise Prescription (TMEP): Advancing the Era of Exercise Medicine Sulin Cheng1,2,3,4, Moritz Schumann()2,4 and Wilhelm Bloch4 1Exercise, Health and Technology Center, Department of Physical Education, Shanghai Jiao Tong University, Shanghai, China 2Exercise Translational Medicine Center, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China 3Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland 4Department of Molecular and Cellular Sport Medicine, German Sport University, Cologne, Germany © The Authors "Exercise is medicine" has gained popularity worldwide after the American Medical Association and the American College of Sports Medicine co-launched their ground-breaking health initiative in 20071 . This initiative was aimed at improving population health and well-being, mainly by raising the awareness of healthcare providers to regard performing physical activity (PA) as one of the vital signs. Ever since, this concept has spread worldwide and PA has been proposed as an essential part of treatment for chronic diseases2 . In their pioneering work, Pedersen and Saltin provided compelling evidence for the role of exercise as the first- or second-line therapy for at least 26 diseases2 . These findings are further corroborated by meta-epidemiological data, indicating exercise interventions to be as effective as drug interventions, such as during rehabilitation after stroke and for the treatment of heart failure3 . However, the overall effect appears to be strongly correlated with important determinants of the exercise program performed (i.e. dose of training [frequency, volume, intensity], type of exercise and adherence to the training program) and disease-related specifics4 , thus requiring not only clinical expertise but also an in-depth understanding of exercise physiology and biology. In this new journal-Translational Medicine and Exercise Prescription (TMEP), we are aiming to bring together the fields of exercise physiology and biology, sports medicine and the science of physical training and testing to bridge the gap between mechanistic research and clinical practice. The journal covers nine sections, including obesity, diabetes, cancer, cardiovascular diseases, neurological and psychiatric diseases, pulmonary diseases, musculoskeletal diseases, endocrine disorders as well as advanced exercise prescription and health maintenance. In this first issue of TMEP, we are delighted to present seven papers from different areas of translational research performed in humans on specific themes related to the treatment and prevention of chronic diseases. Appropriate selection of primary and secondary endpoints is critical for successfully designing translational studies. In the first paper of this issue, TMEP Section Editor, Jörn Rittweger provides his thoughts on "What Are Good Muscle Endpoints for Translational Studies?". In his important work, he highlights the importance of muscles for our health because of their size, their involvement in energy metabolism and their relevance for locomotion. He further suggests that at least eight different muscle functions are important to health. Well accepted methods exist for three relevant muscular endpoints, namely for power, strength and muscle mass, and these endpoints are utilized in clinical studies. However, such validated methods lack a number of additional muscle functions that are not yet fully scientifically explored. This applies foremost to not only the metabolic functions of muscles, but also to their role in storage and dissipation of mechanical energy. His work concludes by emphasizing how physiological knowledge can be an important base for the guidance of clinical diagnostics. Following this important message, the group of TMEP Section Editor Pieter de Lange shares their work entitled "Exercise with Energy Restriction as a Means of Losing Body Mass While Preserving Muscle Quality and Ameliorating Comorbidities: Towards A Therapy for Obesity?". Obesity and related comorbidities have reached pandemic proportions worldwide, particularly during the past decade. Therefore, finding effective intervention strategies not only requires scientific focus but these strategies are also of public interest. Based on both human and animal studies, this narrative review summarizes the effects of dietary and exercise-based programs on loss of different body mass components. Furthermore, both the gain and lack of loss of lean mass in view of muscle quality maintenance are discussed and data related to the mechanisms underlying the conservation of functional muscle mass provided. They also provide evidence of the interaction between energy restriction by diet and exercise-induced metabolic demands at the molecular level. This insight into the mechanisms underlines the relevance of translational considerations for personalized exercise prescription. Obesity and an unhealthy lifestyle are also known to be among the risk factors for type 2 diabetes (T2DM). The research group of TMEP Section Editor Thomas Yates highlights research opportunities and challenges for combining exercise and medical therapies by means of a narrative review entitled "Exercise, Pharmaceutical Therapies and Type 2 Diabetes: Looking beyond Glycemic Control to Whole Body Health and Function". The authors provide evidence on newer generations of glucose-lowering therapies that also induce concomitant weight loss, particularly on glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is). Based on current knowledge, they stress the importance of investigating the interaction or synergy between exercise and other glucose-lowering or weight loss therapies, to make exercise a tailored therapy rather than a generic treatment in the management of T2DM. This review, therefore, clearly highlights the need of precise exercise prescription, originating from an in-depth mechanistic understanding of the effects of exercise. Cancer is another important metabolic and chronic inflammatory disease that may also be associated with obesity. TMEP Section Editor Jesper F Christensen and Associate Editor Ciaran M Fairman provide a very interesting viewpoint in their article,"Targeted Exercise Training for Cancer Patients: Moving beyond Generic Exercise Guidelines in Clinical Oncology". This paper aims to update the current knowledge and the clinical rationale for targeted exercise interventions in exercise oncology. Moreover, a framework for systematic guidance of the design and execution of targeted exercise interventions in oncology is presented. The authors hope that their framework can encourage further research into targeted exercise interventions in oncology and may also be used as a guideline for the design of future trials to increase quality and impact. The group of TMEP Section Editor Helen Dawes, shares their original data in the context of neurological and psychiatric diseases in the article entitled "Physical Activity and Fatigue in Multiple Sclerosis: Secondary Outcomes from a Double-blinded Randomized Controlled Trial of Cocoa Flavonoid Drinks". In this study, they performed intensive phenotyping of the inter-relationships of the time of day, physical activity levels and fatigue to determine exercise prescription in a group of people with multiple sclerosis (MS) participating in a six-week randomized controlled trial of morning flavonoid intake. It was found that fatigue levels increased during the day and higher levels of fatigue reduced physical activity; yet physical activity itself did not lead to increased fatigue. Additionally, morning cocoa intake reduced daytime fatigue and fatigue related to subsequent physical activity. Therefore, combined prescription of morning exercise and dietary flavonoids may optimize the exercise and physical activity potential in people with MS. This study nicely demonstrates the importance of understanding and considering possible covariants such as nutrition and chronobiology to determine an optimal exercise prescription model. TMEP Section Editor Jonathan Myers and colleague Baruch Vainshelboim present a narrative review on "Resistance Training for Rehabilitation of Patients with Idiopathic Pulmonary Fibrosis". In this paper, the pathophysiology and clinical manifestations of Idiopathic Pulmonary Fibrosis (IPF) are summarized with an emphasis on the numerous health and clinical benefits of resistance training among older adults and patients with this respiratory disease. This article effectively explores the potential mechanisms by which systematic resistance training may help overcome exercise limitations in IPF, providing a therapeutic opportunity for rehabilitation. Furthermore, the authors provide important recommendations for pulmonary rehabilitation programs that are based on resistance training for patients with IPF. With this paper, the authors highlight that disease-adapted exercise prescription requires a pathophysiological understanding to justify the inclusion of specific exercise regimens. In the final paper of this special issue, the research group of Section Editor Anthony C Hackney shares their original data on the "Energy Availability and RED-S Risk Factors in Competitive, Non-elite Male Endurance Athletes". This paper particularly emphasizes the entire spectrum of TMEP, that is more than just the most common types of non-communicable diseases, but also includes chronic conditions that may be for example induced by athletic training. In this study, the authors assessed the associations of energy availability and risk factors of relative energy deficiency in sport (RED-S) in 60 competitive, recreationally trained male endurance athletes. They found that hormonal and bone biomarkers were within normal clinical ranges, even when the energy availability was low. The authors further state that athletes are considered at a high risk for RED-S if their energy availability is low (<30 kcal/kg FFM), which is based primarily upon research in women. However, the included recreationally trained male endurance athletes were below this criterion but displayed no RED-S symptomology. Thus, the authors suggest that the <30 kcal/kg FFM criterion may not be a valid categorization for a high risk of RED-S in non-elite male endurance athletes, highlighting the importance of using other criteria. While the purpose of this first issue is to stimulate further discussion on the topic of translational medicine and exercise prescription from different disciplines, we wish to highlight that these topics are not exhaustive and there are many more questions that must be addressed. With TMEP, we aim to introduce a platform for the transparent dissemination of research findings, where special consideration will be given to novel types of exercise prescriptions, including technology-based intervention approaches as well as mechanism-driven studies with translation to exercise prescription. Moreover, TMEP encourages submissions of "negative findings" and/or possible reports of harmful adverse events (e.g. if trials are terminated prematurely) as long as the quality of the study can be assured (i.e. indicated by relevance/novelty of the question, rigorous methodology, transparency and reproducibility). We strongly encourage submissions from all parts of the world to further improve our understanding on exercise prescription based on mechanistic approaches and by that commence a new era of evidence-based precision exercise medicine.