A 10-step participatory program for developing, implementing, and evaluating physical activity promoting actions in nursing homes in Germany.

BACKGROUND: Since multidimensional barriers challenge nursing homes, a socio-ecological approach is needed for physical activity promotion in this setting. So far, little is known about how such an approach can be transferred into the successful development and implementation of PA-promoting actions together with stakeholders on-site. We aimed to investigate the actions and dimensions of PA-promoting actions and their sustainable implementation. To contribute to closing this gap, we present a 10-step program for co-developing and co-evaluating PA-promoting actions in nursing homes through an integrated counselling approach. METHODS: We used a multiple case study approach that built upon manifold data sources, collected in 7 nursing homes over 3 years between 2021 and 2023. We collected fieldnotes and photologs from 14 future workshops (2 per home); 7 evaluation workshops (1 per home); 36 individual counsellings (2 sessions per resident), as well as 87 implementation protocols (action type and frequency), 11 evaluation questionnaires (changes among resources, cooperations, and collaborations); 7 goal attainment scales and 18 individual activity schedules. In addition, we retrieved and documented progress information at regular intervals by phone or email. RESULTS: With staff, residents, relatives, and volunteers, we co-developed 112 ideas for PA promotion; from which 54 ideas were implemented and integrated into everyday life, differentiated into "activities of daily living," "structured activities," and "activity-friendly environments."; 18 residents in 4 homes participated in individual counselling to develop individual activity schedules. Eighteen actions were rated as "(much) more successful than expected"; 10 "(much) worse than expected," and 23 "as successful as expected." Three actions were not evaluated. DISCUSSION: The participatory integrated counselling approach led to home-specific actions and promoted implementation into everyday life. The number and dimensions of actions implemented largely depended on the mission and vision of the respective home. The lack of staff could partially be compensated for by involving neighbourhoods, volunteers, and community organisations, such as local clubs. CONCLUSION: To effectively promote PA in nursing homes, a tailored approach considering structural conditions, locations, volunteer engagement, and organisational visions is essential. Long-lasting partnerships and low-threshold opportunities prove promising. Future research should delve into structural-level change processes and outcomes in this context.

Physical Activity, Sedentary Behavior, and Their Predictors Among Nursing Home Residents-Cross-Sectional Results of the BaSAlt Study.

Little is known about physical activity (PA) and sedentary behavior (SB) among nursing home residents although PA is known as a health promoter. This study examined PA, SB, and their predictors among nursing home residents (n = 63). Dependent variables were accelerometry-based PA and SB. Predictor variables included in a path analysis were age, sex, body mass index, Barthel Index, cognitive status (Mini-Mental State Examination), physical performance (hand grip strength and habitual walking speed), and well-being (World Health Organization-5 well-being index). PA was very low (M steps per day = 2,433) and SB was high (M percentage of sedentary time = 89.4%). PA was significantly predicted by age (ß = -0.27, p = .008), body mass index (ß = -0.29, p = .002), Barthel Index (ß = 0.24, p = .040), and hand grip strength (ß = 0.30, p = .048). SB was significantly predicted by body mass index (ß = 0.27, p = .008) and Barthel Index (ß = -0.30, p = .012). Results might be helpful for everyday practice to identify individuals at high risk for low PA and high SB.

The Acute, Short-, and Long-Term Effects of Endurance Exercise on Skeletal Muscle Transcriptome Profiles.

A better understanding of the cellular and molecular mechanisms that are involved in skeletal muscle adaptation to exercise is fundamentally important to take full advantage of the enormous benefits that exercise training offers in disease prevention and therapy. The aim of this study was to elucidate the transcriptional signatures that distinguish the endurance-trained and untrained muscles in young adult males (24 ± 3.5 years). We characterized baseline differences as well as acute exercise-induced transcriptome responses in vastus lateralis biopsy specimens of endurance-trained athletes (ET; n = 8; VO2max, 67.2 ± 8.9 mL/min/kg) and sedentary healthy volunteers (SED; n = 8; VO2max, 40.3 ± 7.6 mL/min/kg) using microarray technology. A second cohort of SED volunteers (SED-T; n = 10) followed an 8-week endurance training program to assess expression changes of selected marker genes in the course of skeletal muscle adaptation. We deciphered differential baseline signatures that reflected major differences in the oxidative and metabolic capacity of the endurance-trained and untrained muscles. SED-T individuals in the training group displayed an up-regulation of nodal regulators of oxidative adaptation after 3 weeks of training and a significant shift toward the ET signature after 8 weeks. Transcriptome changes provoked by 1 h of intense cycling exercise only poorly overlapped with the genes that constituted the differential baseline signature of ETs and SEDs. Overall, acute exercise-induced transcriptional responses were connected to pathways of contractile, oxidative, and inflammatory stress and revealed a complex and highly regulated framework of interwoven signaling cascades to cope with exercise-provoked homeostatic challenges. While temporal transcriptional programs that were activated in SEDs and ETs were quite similar, the quantitative divergence in the acute response transcriptomes implicated divergent kinetics of gene induction and repression following an acute bout of exercise. Together, our results provide an extensive examination of the transcriptional framework that underlies skeletal muscle plasticity.

[Sarcopenia, physical activity and sedentary behavior among nursing home residents in Germany]. / Sarkopenie, körperliche Aktivität und sedentäres Verhalten von Pflegeheimbewohnenden in Deutschland.

BACKGROUND: Residents in nursing homes show a high prevalence of the musculoskeletal syndrome sarcopenia and tend not to achieve current physical activity recommendations. OBJECTIVE: The aim of this study is to identify differences in physical activity and sedentary behavior of sarcopenic residents compared with nonsarcopenic and presarcopenic residents. METHODS: Sarcopenia assessment was performed among 63 nursing home residents in Baden-Wuerttemberg (D) using the European Working Group on Sarcopenia in Older People 2 specifications. Structured activity sessions (per week), accelerometer-based physical activity (steps/day), and sedentary behavior (percentual/day) were examined. The group comparisons were determined with Kruskal-Wallis tests and Dunn-Bonferroni post hoc tests. RESULTS: Significant differences were found for number of steps (p = 0.005) and percentual sedentary behavior (p = 0.019). Moreover, steps per day presented significant results in group comparison for no sarcopenia (2824.4 [423-14275]) with probable sarcopenia (1703.9 [118-5663]) and confirmed/severe sarcopenia (1571.2 [240-2392]) (both p = 0.022; |r| = 0.34). Sedentary behavior demonstrated significant differences in groups with no sarcopenia (87.9% [69.1-94.3]) and with probable sarcopenia (91.7% [80.4-9835]) (p = 0.018; |r| = 0.35). CONCLUSION: Nonsarcopenic residents demonstrated a higher number of steps and lower sedentary behavior compared with presarcopenic and sarcopenic residents. Increasing steps, reducing sedentary behavior and promoting activities of daily living can contribute to the prevention and treatment of sarcopenia in the nursing home setting.

Acute and long-term exercise adaptation of adipose tissue and skeletal muscle in humans: a matched transcriptomics approach after 8-week training-intervention.

BACKGROUND: Exercise exerts many health benefits by directly inducing molecular alterations in physically utilized skeletal muscle. Molecular adaptations of subcutaneous adipose tissue (SCAT) might also contribute to the prevention of metabolic diseases. AIM: To characterize the response of human SCAT based on changes in transcripts and mitochondrial respiration to acute and repeated bouts of exercise in comparison to skeletal muscle. METHODS: Sedentary participants (27 ± 4 yrs) with overweight or obesity underwent 8-week supervised endurance exercise 3×1h/week at 80% VO2peak. Before, 60 min after the first and last exercise bout and 5 days post intervention, biopsies were taken for transcriptomic analyses and high-resolution respirometry (n = 14, 8 female/6 male). RESULTS: In SCAT, we found 37 acutely regulated transcripts (FC > 1.2, FDR < 10%) after the first exercise bout compared to 394, respectively, in skeletal muscle. Regulation of only 5 transcripts overlapped between tissues highlighting their differential response. Upstream and enrichment analyses revealed reduced transcripts of lipid uptake, storage and lipogenesis directly after exercise in SCAT and point to ß-adrenergic regulation as potential major driver. The data also suggest an exercise-induced modulation of the circadian clock in SCAT. Neither term was associated with transcriptomic changes in skeletal muscle. No evidence for beigeing/browning was found in SCAT along with unchanged respiration. CONCLUSIONS: Adipose tissue responds completely distinct from adaptations of skeletal muscle to exercise. The acute and repeated reduction in transcripts of lipid storage and lipogenesis, interconnected with a modulated circadian rhythm, can counteract metabolic syndrome progression toward diabetes.

The impact of rehabilitation sport on breast cancer-related lymphoedema and quality of life.

PURPOSE: Surgery and radiotherapy as part of breast cancer treatment can lead to lymphoedema of the upper extremities (breast cancer-related lymphoedema = BCRL) and reduce the quality of life (health-related quality of life = HRQoL). The aim of the present study was to investigate the influence of paddling in a dragon boat (PP) on HRQoL and BCRL in breast cancer survivors (BCS). METHODS: Between April and October 2017, a prospective case-control study evaluated the effects of PP compared to a control group. In the paddle group (n = 28), weekly arm circumference measurements were taken at four defined anatomic areas of the arm before and after training; in the control group (n = 70), the measurements were taken once a month. At the beginning and end of the study, questionnaires from both groups (SF 36, EORTC QLQ C30) were evaluated to understand the differences in HRQoL. RESULTS: The paddle group started with a higher HRQoL compared to the control group. Most interesting, whether the affected or unaffected arm, whether before or after training-the arm circumference decreased over time in the paddling group. A pre-existing lymphoedema was not negatively influenced by paddling. In the paddle group, the physical health was constant over the season, while the physical health of the control group decreased significantly over time. CONCLUSION: PP in a dragon boat does not lead to the development or worsening of pre-existing lymphoedema due to breast cancer therapy, and seems to have a positive effect on the quality of life.

Prevalence of pathological FFRCT values without coronary artery stenosis in an asymptomatic marathon runner cohort.

OBJECTIVES: To evaluate computed tomography fractional flow reserve (FFRCT) values in distal parts of the coronaries in an asymptomatic cohort of marathon runners without any coronary stenosis for potentially false-positive values. METHODS: Ninety-eight asymptomatic male marathon runners (age 53 ± 7 years) were enrolled in a prospective monocentric study and underwent coronary computed tomography angiography (CCTA). CCTA data were analyzed for visual coronary artery stenosis. FFRCT was evaluated in 59 participants without coronary artery stenosis in proximal, mid, and distal coronary sections using an on-site software prototype. RESULTS: In participants without coronary artery stenosis, abnormal FFRCT values ≤ 0.8 in distal segments were found in 22 participants (37%); in 19 participants in the LAD; in 5 participants in the LCX; and in 4 participants in the RCA. Vessel diameters in participants with FFRCT values > 0.80 compared to ≤ 0.80 were 1.6 ± 0.3 mm versus 1.5 ± 0.3 mm for distal LAD (p = 0.025), 1.8 ± 0.3 mm versus 1.6 ± 0.5 mm for distal LCX (p = 0.183), and 2.0 ± 0.4 mm versus 1.5 ± 0.2 mm for distal RCA (p < 0.001). CONCLUSIONS: Abnormal FFRCT values of ≤ 0.8 frequently occurred in distal coronary segments in subjects without any anatomical coronary artery stenosis. This effect is only to some degree explainable by small distal vessel diameters. Therefore, the validity of hemodynamic relevance evaluation using FFRCT in distal coronary artery segment stenosis is reduced. KEY POINTS: • Abnormal FFRCT values (≤ 0.8) occurred in over a third of the subjects in the distal LAD despite the absence of coronary artery stenosis.. • Therefore, the validity of hemodynamic relevance evaluation in distal coronary artery segment stenosis is reduced. • Decision-making based on abnormal FFRCT values in distal vessel sections should be performed with caution and only in combination with visual assessment of the grade of stenosis..

Individual cardiovascular responsiveness to work-matched exercise within the moderate- and severe-intensity domains.

PURPOSE: We investigated the cardiovascular individual response to 6 weeks (3×/week) of work-matched within the severe-intensity domain (high-intensity interval training, HIIT) or moderate-intensity domain (moderate-intensity continuous training, MICT). In addition, we analyzed the cardiovascular factors at baseline underlying the response variability. METHODS: 42 healthy sedentary participants were randomly assigned to HIIT or MICT. We applied the region of practical equivalence-method for identifying the levels of responders to the maximal oxygen uptake (V̇O2max) response. For investigating the influence of cardiovascular markers, we trained a Bayesian machine learning model on cardiovascular markers. RESULTS: Despite that HIIT and MICT induced significant increases in V̇O2max, HIIT had greater improvements than MICT (p < 0.001). Greater variability was observed in MICT, with approximately 50% classified as "non-responder" and "undecided". 20 "responders", one "undecided" and no "non-responders" were observed in HIIT. The variability in the ∆V̇O2max was associated with initial cardiorespiratory fitness, arterial stiffness, and left-ventricular (LV) mass and LV end-diastolic diameter in HIIT; whereas, microvascular responsiveness and right-ventricular (RV) excursion velocity showed a significant association in MICT. CONCLUSION: Our findings highlight the critical influence of exercise-intensity domains and biological variability on the individual V̇O2max response. The incidence of "non-responders" in MICT was one third of the group; whereas, no "non-responders" were observed in HIIT. The incidence of "responders" was 11 out of 21 participants in MICT, and 20 out of 21 participants in HIIT. The response in HIIT showed associations with baseline fitness, arterial stiffness, and LV-morphology; whereas, it was associated with RV systolic function in MICT.

Effects of Training Status and Exercise Mode on Global Gene Expression in Skeletal Muscle.

The aim of this study was to investigate differences in skeletal muscle gene expression of highly trained endurance and strength athletes in comparison to untrained individuals at rest and in response to either an acute bout of endurance or strength exercise. Endurance (ET, n = 8, VO2max 67 ± 9 mL/kg/min) and strength athletes (ST, n = 8, 5.8 ± 3.0 training years) as well as untrained controls (E-UT and S-UT, each n = 8) performed an acute endurance or strength exercise test. One day before testing (Pre), 30 min (30'Post) and 3 h (180'Post) afterwards, a skeletal muscle biopsy was obtained from the m. vastus lateralis. Skeletal muscle mRNA was isolated and analyzed by Affymetrix-microarray technology. Pathway analyses were performed to evaluate the effects of training status (trained vs. untrained) and exercise mode-specific (ET vs. ST) transcriptional responses. Differences in global skeletal muscle gene expression between trained and untrained were smaller compared to differences in exercise mode. Maximum differences between ET and ST were found between Pre and 180'Post. Pathway analyses showed increased expression of exercise-related genes, such as nuclear transcription factors (NR4A family), metabolism and vascularization (PGC1-α and VEGF-A), and muscle growth/structure (myostatin, IRS1/2 and HIF1-α. The most upregulated genes in response to acute endurance or strength exercise were the NR4A genes (NR4A1, NR4A2, NR4A3). The mode of acute exercise had a significant effect on transcriptional regulation Pre vs. 180'Post. In contrast, the effect of training status on human skeletal muscle gene expression profiles was negligible compared to strength or endurance specialization. The highest variability in gene expression, especially for the NR4A-family, was observed in trained individuals at 180'Post. Assessment of these receptors might be suitable to obtain a deeper understanding of skeletal muscle adaptive processes to develop optimized training strategies.

[Twin research in Germany]. / Medizinische Zwillingsforschung in Deutschland.

The worldwide development of twin cohorts began after World War II. These cohorts now include around 1.5 million twins, and more than 2748 twin studies have been published between 1950 and 2012. Each year, the number of twin publications increases by another 500 to 1000. The underrepresentation of German twin studies cannot be solely explained by the abuse of medical research under National Socialism. Developing and expanding large twin cohorts is a challenge in terms of both ethics and data protection. However, twin cohorts enable long-term and real-time research on many medical issues and contribute to answer the question of predisposition or environment as possible disease triggers - even after the sequencing of the human genome.There are currently two German twin cohorts: the biomedical cohort HealthTwiSt, with around 1500 pairs of twins, and TwinLife, a sociological-psychological cohort with around 4000 pairs of twins. There are also disease-specific cohorts. The TwinHealth Consortium in the Faculty of Medicine at the University of Tübingen was established in 2016 with the aim of enabling open-ended and sustainable twin research in Tübingen to answer various scientific questions.With the help of systematic literature research and medical history, this article gives an overview of the worldwide development of twin studies and databases over the last 100 years. The example of the Tübingen TwinHealth Initiative illuminates the structure of a twin cohort and its legal, ethical, and data protection aspects.

Transcriptional memory in skeletal muscle. Don't forget (to) exercise.

Transcriptional memory describes an ancient and highly conserved form of cellular learning that enables cells to benefit from recent experience by retaining a mitotically inheritable but reversible memory of the initial transcriptional response when encountering an environmental or physiological stimulus. Herein, we will review recent progress made in the understanding of how cells can make use of diverse constituents of the epigenetic toolbox to retain a transcriptional memory of past states and perturbations. Specifically, we will outline how these mechanisms will help to improve our understanding of skeletal muscle plasticity in health and disease. We describe the epigenetic road map that allows skeletal muscle fibers to navigate through training-induced adaptation processes, and how epigenetic memory marks can preserve an autobiographical history of lifestyle behavior changes, pathological challenges, and aging. We will further consider some key findings in the field of exercise epigenomics to emphasize major challenges when interpreting dynamic changes in the chromatin landscape in response to acute exercise and training.

Identification and regulation of the xenometabolite derivatives cis- and trans-3,4-methylene-heptanoylcarnitine in plasma and skeletal muscle of exercising humans.

Little is known about xenometabolites in human metabolism, particularly under exercising conditions. Previously, an exercise-modifiable, likely xenometabolite derivative, cis-3,4-methylene-heptanoylcarnitine, was reported in human plasma. Here, we identified trans-3,4-methylene-heptanoylcarnitine, and its cis-isomer, in plasma and skeletal muscle by liquid chromatography-mass spectrometry. We analyzed the regulation by exercise and the arterial-to-venous differences of these cyclopropane ring-containing carnitine esters over the hepatosplanchnic bed and the exercising leg in plasma samples obtained in three separate studies from young, lean and healthy males. Compared with other medium-chain acylcarnitines, the plasma concentrations of the 3,4-methylene-heptanoylcarnitine isomers only marginally increased with exercise. Both isomers showed a more than twofold increase in the skeletal muscle tissue of the exercising leg; this may have been due to the net effect of fatty acid oxidation in the exercising muscle and uptake from blood. The latter idea is supported by a more than twofold increased net uptake in the exercising leg only. Both isomers showed a constant release from the hepatosplanchnic bed, with an increased release of the trans-isomer after exercise. The isomers differ in their plasma concentration, with a four times higher concentration of the cis-isomer regardless of the exercise state. This is the first approach studying kinetics and fluxes of xenolipid isomers from tissues under exercise conditions, supporting the hypothesis that hepatic metabolism of cyclopropane ring-containing fatty acids is one source of these acylcarnitines in plasma. The data also provide clear evidence for an exercise-dependent regulation of xenometabolites, opening perspectives for future studies about the physiological role of this largely unknown class of metabolites.

Predictive Ability of a Laboratory Performance Test in Mountain Bike Cross-country Olympic Athletes.

Mountain bike Cross-Country Olympic (XCO) has an intermittent performance profile, underlining the importance of anaerobic metabolism. Traditional performance tests in cycling primarily quantify aerobic metabolism and inadequately meet the demands in XCO. The aim was therefore to validate a specific test that quantifies these requirements by means of an XCO race.Twenty-three competitive XCO athletes (17.9±3.6 years) performed a previously developed performance test and an XCO race within one week. Correlations between individual anaerobic threshold (IAT), 4 mmol lactate threshold (LT4), maximal aerobic power (MAP), maximal effort time trials (TT) for 10-300 s and mean power output of the race (POR) were calculated. In addition, a multiple regression model of the predictive value of the test was calculated.Variables correlated significantly (p<.01) with POR: IAT (r=.81), LT4 (r=0.79), MAP (r=0.91), TT10 (r=0.75), TT30 (r=0.85), TT60 (r=0.84) and TT300 (r=0.86). In the regression model, sex and body mass were set influencing variables (R²adj.=0.70), whereby MAP had the highest correlation with POR and significantly improved the predictive value of the model (R²adj.=0.86).The high correlation of collected performance variables with POR indicated the MTB-PT's additional benefit for performance testing in XCO because it is specific but very feasible.

Quality Control of Serum and Plasma by Quantification of (4E,14Z)-Sphingadienine-C18-1-Phosphate Uncovers Common Preanalytical Errors During Handling of Whole Blood.

BACKGROUND: Nonadherence to standard operating procedures (SOPs) during handling and processing of whole blood is one of the most frequent causes affecting the quality of serum and plasma. Yet, the quality of blood samples is of the utmost importance for reliable, conclusive research findings, valid diagnostics, and appropriate therapeutic decisions. METHODS: UHPLC-MS-driven nontargeted metabolomics was applied to identify biomarkers that reflected time to processing of blood samples, and a targeted UHPLC-MS analysis was used to quantify and validate these biomarkers. RESULTS: We found that (4E,14Z)-sphingadienine-C18-1-phosphate (S1P-d18:2) was suitable for the reliable assessment of the pronounced changes in the quality of serum and plasma caused by errors in the phase between collection and centrifugation of whole blood samples. We rigorously validated S1P-d18:2, which included the use of practicality tests on >1400 randomly selected serum and plasma samples that were originally collected during single- and multicenter trials and then stored in 11 biobanks in 3 countries. Neither life-threatening disease states nor strenuous metabolic challenges (i.e., high-intensity exercise) affected the concentration of S1P-d18:2. Cutoff values for sample assessment were defined (plasma, ≤0.085 µg/mL; serum, ≤0.154 µg/mL). CONCLUSIONS: Unbiased valid monitoring to check for adherence to SOP-dictated time for processing to plasma or serum and/or time to storage of whole blood at 4 °C is now feasible. This novel quality assessment step could enable scientists to uncover common preanalytical errors, allowing for identification of serum and plasma samples that should be excluded from certain investigations. It should also allow control of samples before long-term storage in biobanks.

Effects of extracellular orotic acid on acute contraction-induced adaptation patterns in C2C12 cells.

Dietary administration of orotic acid (OA), an intermediate in the pyrimidine biosynthetic pathway, is considered to provide a wide range of beneficial effects, including cardioprotection and exercise adaptation. Its mechanisms of action, when applied extracellularly, however, are barely understood. In this study, we evaluated potential effects of OA on skeletal muscle using an in vitro contraction model of electrically pulse-stimulated (EPS) C2C12 myotubes. By analyzing a subset of genes representing inflammatory, metabolic, and structural adaptation pathways, we could show that OA supplementation diminishes the EPS-provoked expression of inflammatory transcripts (interleukin 6, Il6; chemokine (C-X-C Motif) ligand 5, Cxcl5), and attenuated transcript levels of nuclear receptor subfamily 4 group A member 3 (Nr4A3), early growth response 1 (Egr1), activating transcription factor 3 (Atf3), and fast-oxidative MyHC-IIA isoform (Myh2). By contrast, OA had no suppressive effect on the pathogen-provoked inflammatory gene response in skeletal muscle cells, as demonstrated by stimulation of C2C12 myotubes with bacterial LPS. In addition, we observed a suppressive effect of OA on EPS-induced phosphorylation of AMP-activated protein kinase (AMPK), whereas EPS-triggered phosphorylation/activation of the mammalian target of rapamycin (mTOR) was not affected. Finally, we demonstrate that OA positively influences glycogen levels in EP-stimulated myotubes. Taken together, our results suggest that in skeletal muscle cells, OA modulates both the inflammatory and the metabolic reaction provoked by acute contraction. These results might have important clinical implications, specifically in cardiovascular and exercise medicine.

Mid-term development of the right ventricle in competitive athletes.

BACKGROUND: Long-term intensive training induces physiological, morphological, and functional adaption of the athlete's heart. PURPOSE: To evaluate the development of athlete's heart during a mid-term follow-up of competitive athletes using cardiac magnetic resonance (CMR). MATERIAL AND METHODS: Eighteen competitive long-distance runners and triathletes (age 43 ± 13 years, 3 women) were prospectively examined in a longitudinal follow-up study 5.05 ± 0.6 years after baseline. CMR at 1.5-T was performed for functional and late gadolinium enhancement (LGE) imaging. Left ventricular (LV) and right ventricular (RV) end-diastolic volume (LVEDV, RVEDV) as well as ejection fraction (LVEF, RVEF), LV myocardial mass (LVMM), and atrial sizes were determined and compared to baseline in matched pairs statistics for paired difference. RESULTS: LVEDV (197 ± 38 mL vs. 196 ± 38 mL, paired difference -0.9 mL, P = 0.7) and LVEF (62 ± 7% vs. 62 ± 5%, paired difference 0.1%, P = 0.9) did not change during the follow-up period, whereas LVMM increased significantly (149 ± 31 g vs.164 ± 32 g, paired difference 14 g, P < 0.0001). RVEDV significantly increased from 221 ± 47 mL at baseline to 230 ± 52 mL (paired difference 10 mL, P = 0.0033). RVEF decreased from baseline 57 ± 8% to 53 ± 7% (paired difference -3%, P = 0.0234). Left atrial size showed no significant changes (24 ± 5 cm2 vs. 25 ± 6 cm2, paired difference 0.5 cm2, P = 0.17) and right atrial size increased significantly (30 ± 5 cm2 vs. 32 ± 4 cm2, paired difference 2 cm2, P = 0.0054). CONCLUSION: This study supports the theory of ongoing remodeling in an athlete's heart. Predominantly the right heart can further enlarge in a mid-term period. This response seems not linearly dependent on a steady, decreased, or increased training volume.

Sex-specific variation in signaling pathways and gene expression patterns in human leukocytes in response to endotoxin and exercise.

BACKGROUND: While exercise effects on the immune system have received increasing attention in recent years, it remains unclear to what extent gender and fluctuations in sex hormones during menstrual cycle influence immunological responses to exercise. METHODS: We investigated mRNA changes induced through exhaustive exercise (half-marathon; pre-exercise and post-exercise [30 min, 3 h, 24 h] on whole blood cultures ± lipopolysaccharide [LPS] [1 h]) with a specific focus on sex differences (men vs women in luteal phase) as an extension of our previous study. RESULTS: Inflammation related signaling pathways, TLRs, cytosolic DNA sensing and RIG-I like receptors were differentially activated between sexes in LPS-stimulated cultures. Genes differentially regulated between sexes included TNIP-1, TNIP-3, IL-6, HIVEP1, CXCL3, CCR3, IL-8, and CD69, revealing a bias towards less anti-inflammatory gene regulation in women compared to men. In addition, several genes relevant to brain function (KMO, DDIT4, VEGFA, IGF1R, IGF2R, and FGD4) showed differential activation between sexes. Some of these genes (e.g., KMO in women, DDIT4 in both sexes) potentially constitute neuroprotective mechanisms. CONCLUSIONS: These data reveal that the exercise-induced change in gene expression might be gender and menstrual cycle phase dependent.

Effects of Acute Endurance Exercise on Plasma Protein Profiles of Endurance-Trained and Untrained Individuals over Time.

Acute physical exercise and repeated exercise stimuli affect whole-body metabolic and immunologic homeostasis. The aim of this study was to determine plasma protein profiles of trained (EET, n = 19) and untrained (SED, n = 17) individuals at rest and in response to an acute bout of endurance exercise. Participants completed a bicycle exercise test at an intensity corresponding to 80% of their VO2max. Plasma samples were taken before, directly after, and three hours after exercise and analyzed using multiplex immunoassays. Seventy-eight plasma variables were included in the final analysis. Twenty-nine variables displayed significant acute exercise effects in both groups. Seven proteins differed between groups, without being affected by acute exercise. Among these A2Macro and IL-5 were higher in EET individuals while leptin showed elevated levels in SED individuals. Fifteen variables revealed group and time differences with elevated levels for IL-3, IL-7, IL-10, and TNFR2 in EET individuals. An interaction effect could be observed for nine variables including IL-6, MMP-2, MMP-3, and muscle damage markers. The proteins that differ between groups indicate a long-term exercise effect on plasma protein concentrations. These findings might be of importance in the development of exercise-based strategies in the prevention and therapy of chronic metabolic and inflammatory diseases and for training monitoring.

Exercise, skeletal muscle and inflammation: ARE-binding proteins as key regulators in inflammatory and adaptive networks.

The role of inflammation in skeletal muscle adaptation to exercise is complex and has hardly been elucidated so far. While the acute inflammatory response to exercise seems to promote skeletal muscle training adaptation and regeneration, persistent, low-grade inflammation, as seen in a multitude of chronic diseases, is obviously detrimental. The regulation of cytokine production in skeletal muscle cells has been relatively well studied, yet little is known about the compensatory and anti-inflammatory mechanisms that resolve inflammation and restore tissue homeostasis. One important strategy to ensure sequential, timely and controlled resolution of inflammation relies on the regulated stability of mRNAs encoding pro-inflammatory mediators. Many key transcripts in early immune responses are characterized by the presence of AU-rich elements (AREs) in the 3'-untranslated regions of their mRNAs, allowing efficient fine-tuning of gene expression patterns at the post-transcriptional level. AREs exert their function by recruiting particular RNA-binding proteins, resulting, in most cases, in de-stabilization of the target transcripts. The best-characterized ARE-binding proteins are HuR, CUGBP1, KSRP, AUF1, and the three ZFP36 proteins, especially TTP/ZFP36. Here, we give a general introduction into the role of inflammation in the adaptation of skeletal muscle to exercise. Subsequently, we focus on potential roles of ARE-binding proteins in skeletal muscle tissue in general and specifically exercise-induced skeletal muscle remodeling. Finally, we present novel data suggesting a specific function of TTP/ZFP36 in exercise-induced skeletal muscle plasticity.