Eight weeks of high-intensity interval training versus stretching do not change the psychoneuroendocrine response to a social stress test in emotionally impulsive humans.

PURPOSE: Research supports physical activity as a method to heighten stress resistance and resilience through positive metabolic alterations mostly affecting the neuroendocrine system. High-intensity interval training (HIIT) has been proposed as a highly effective time-saving method to induce those changes. However, existing literature relies heavily on cross-sectional analyses, with few randomised controlled trials highlighting the necessity for more exercise interventions. Thus, this study aims to investigate the effects of HIIT versus an active control group on the stress response to an acute psychosocial stressor in emotionally impulsive humans (suggested as being strong stress responders). METHODS: The study protocol was registered online (DRKS00016589) before data collection. Sedentary, emotionally impulsive adults (30.69 ± 8.20 y) were recruited for a supervised intervention of 8 weeks and randomly allocated to either a HIIT (n = 25) or a stretching group (n = 19, acting as active controls). Participants were submitted to a test battery, including saliva samples, questionnaires (self-efficacy- and perceived stress-related), visual analogue scales (physical exercise- and stress-related), and resting electroencephalography and electrocardiography assessing their reaction to an acute psychological stressor (Trier Social Stress Test) before and after the exercise intervention. RESULTS: HIIT increased aerobic fitness in all participants, whereas stretching did not. Participants from the HIIT group reported perceiving exercising more intensively than those from the active control group (ƞp2 = 0.108, p = 0.038). No further group differences were detected. Both interventions largely increased levels of joy post-TSST (ƞp2 = 0.209, p = 0.003) whilst decreasing tension (ƞp2 = 0.262, p < 0.001) and worries (ƞp2 = 0.113, p = 0.037). Finally, both interventions largely increased perceived levels of general self-efficacy (ƞp2 = 0.120, p = 0.029). CONCLUSION: This study suggests that 8 weeks of HIIT does not change the psychoneuroendocrine response to an acute psychological stress test compared to an active control group in emotionally impulsive humans. Further replications of supervised exercise studies highly powered with active and passive controls are warranted.

The effects of menstrual cycle phases on immune function and inflammation at rest and after acute exercise: A systematic review and meta-analysis.

The immune system plays an important role in mediating exercise responses and adaptations. However, whether fluctuating hormone concentrations across the menstrual cycle may impact these processes remains unknown. The aim of this systematic review with meta-analysis was to compare baseline concentrations as well as exercise-induced changes in immune and inflammatory parameters between menstrual cycle phases. A systematic literature search was conducted according to the PRISMA guidelines using Pubmed/MEDLINE, ISI Web of Science, and SPORTDiscus. Of the 159 studies included in the qualitative synthesis, 110 studies were used for meta-analysis. Due to the designs of the included studies, only the follicular and luteal phase could be compared. The estimated standardized mean differences based on the random-effects model revealed higher numbers of leukocytes (-0.48 [-0.73; -0.23], p < 0.001), monocytes (-0.73 [-1.37; -0.10], p = 0.023), granulocytes (-0.85 [-0.1.48; -0.21], p = 0.009), neutrophils (-0.32 [-0.52; -0.12], p = 0.001), and leptin concentrations (-0.37 [-0.5; -0.23], p = 0.003) in the luteal compared to the follicular phase at rest. Other parameters (adaptive immune cells, cytokines, chemokines, and cell adhesion molecules) showed no systematic baseline differences. Seventeen studies investigated the exercise-induced response of these parameters, providing some indications for a higher pro-inflammatory response in the luteal phase. In conclusion, parameters of innate immunity showed cycle-dependent regulation at rest, while little is known on the exercise responses. Due to a large heterogeneity and a lack of cycle phase standardization among the included studies, future research should focus on comparing at least three distinct hormonal profiles to derive more specific recommendations for exercise prescription.

Influence of a 12-month supervised, intensive resistance, aerobic and impact exercise intervention on muscle strength in prostate cancer patients undergoing anti-hormone therapy: Study protocol for the randomized, controlled Burgdorf study.

INTRODUCTION: Reduced testosterone levels due to androgen deprivation therapy (ADT) in prostate cancer patients cause common side effects, such as reduced muscle strength and bone density, increased fat mass, sexual dysfunction and fatigue. Short-term exercise during ADT has proven to be safe and effective in exhibiting a positive impact on body composition, sexual dysfunction and fatigue. However, there are only three randomized controlled trials that investigate one-year supervised impact exercise interventions, none of which examined follow-up effects after the intervention. Therefore, this study will conduct a one-year impact exercise intervention and assess follow-up effects up to one year later. MATERIAL AND METHODS: The aim of the randomized, controlled Burgdorf study is to assess the effects of a supervised 12-month intensive multimodal exercise intervention in comparison to a moderate aerobic exercise intervention, on muscle strength in prostate cancer patients receiving ADT. Additionally, quality of life, fatigue, body composition, erectile dysfunction, bone pain, physical activity level, endurance capacity, body-mass-index, waist and hip circumference and prostate-specific antigen- and testosterone levels will be assessed up to one year later. DISCUSSION: The Burgdorf study is the first study to conduct two different one-year supervised exercise interventions, and follow-up with patients for up to one year after the intervention. Results could provide important insights into the long-term effects of interventions on those parameters negatively affected by ADT, which could specify or newly establish care structures. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00009975. Registered 2016-02-09, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00009975.

[Clinical, radiological, and histopathological features of pulmonary post-COVID syndrome : A form of autoimmune-mediated interstitial lung disease?] / Klinische, radiologische und histopathologische Merkmale des pulmonalen Post-COVID-Syndroms : Eine Form der autoimmunvermittelten interstitiellen Lungenerkrankung?

BACKGROUND: About 10% of patients develop persistent symptoms after mild/moderate COVID-19. We have previously reported detection of antinuclear autoantibodies/extractable nuclear antigens (ANA/ENA) in patients with severe COVID-19. OBJECTIVES: The aim of this small pilot study was to characterize long-/post-COVID and to evaluate possible similarities between lung involvement in long-/post-COVID and connective tissue disease (CTD). METHODS: We prospectively enrolled 33 previously healthy patients with persistent pulmonal symptoms after mild/moderate COVID-19 without hospitalization (median age, 39 years). We performed clinical evaluation including pulmonary function tests, computed tomography (CT), and serology for ANA/ENA. In 29 of 33 patients, transbronchial biopsies (TBBs) were taken for histopathological assessment. RESULTS: Most patients presented with disturbed oxygen pulse in spiroergometry and slight lymphocytosis in bronchoalveolar lavage (BAL) fluid. The CT pattern showed bronchial wall thickening and increased low-attenuation volume. Autoantibodies were detected in 13 of 33 patients (39.4%). Histopathological assessment showed interstitial lymphocytosis with alveolar fibrin and organizing pneumonia. Ultrastructural analyses revealed interstitial collagen deposition. CONCLUSION: While histopathology of pulmonary long-/post-COVID alone is unspecific, the combination with clinical and radiological features together with detection of autoantibodies would allow for a diagnosis of interstitial pneumonia with autoimmune features (IPAF). Since we observe interstitial collagen deposition and since IPAF/CTD-ILD might progress to fibrosis, the persistence of autoantibodies and possible fibrotic change should be closely monitored in autoantibody-positive long-/post-COVID patients.

The Matrilin-3 T298M mutation predisposes for post-traumatic osteoarthritis in a knock-in mouse model.

OBJECTIVE: The human matrilin-3 T303M (in mouse T298M) mutation has been proposed to predispose for osteoarthritis, but due to the lack of an appropriate animal model this hypothesis could not be tested. This study was carried out to identify pathogenic mechanisms in a transgenic mouse line by which the mutation might contribute to disease development. METHODS: A mouse line carrying the T298M point mutation in the Matn3 locus was generated and features of skeletal development in ageing animals were characterized by immunohistology, micro computed tomography, transmission electron microscopy and atomic force microscopy. The effect of transgenic matrilin-3 was also studied after surgically induced osteoarthritis. RESULTS: The matrilin-3 T298M mutation influences endochondral ossification and leads to larger cartilage collagen fibril diameters. This in turn leads to an increased compressive stiffness of the articular cartilage, which, upon challenge, aggravates osteoarthritis development. CONCLUSIONS: The mouse matrilin-3 T298M mutation causes a predisposition for post-traumatic osteoarthritis and the corresponding knock-in mouse line therefore represents a valid model for investigating the pathogenic mechanisms involved in osteoarthritis development.

Sensorimotor training and whole-body vibration training have the potential to reduce motor and sensory symptoms of chemotherapy-induced peripheral neuropathy-a randomized controlled pilot trial.

Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and clinically relevant side effect of chemotherapy. The symptoms diminish patients' quality of life and represent a decisive limiting factor for medical therapy. To date, effective treatment options are lacking. Specific exercise interventions have proven promising to target relevant symptoms. We conducted a prospective, four-armed, randomized, controlled trial, to evaluate the effects of sensorimotor training (SMT) and whole-body vibration training (WBV) on patients with CIPN. Participants (N = 40) were randomized to either one of two intervention groups (SMT N = 10 or WBV N = 10) or oncological control group (N = 10) and matched by gender and age with a healthy control (N = 10). The intervention groups exercised twice a week for 6 weeks. Primary endpoint was the reduction of CIPN-related symptoms (improve peripheral deep sensitivity, Achilles tendon reflex (ASR) and patellar tendon reflex (PSR), light-touch perception, sense of position, and lower leg strength). Secondary endpoints were nerve conduction velocity and amplitude, balance control, quality of life, and CIPN-related pain. Patients exercising improved sensory and associated motor symptoms. Significant intergroup differences were found for the tendon reflexes (ASR P = .017 and PSR P = .020), peripheral deep sensitivity (P = .010), and pain (P = .043). Furthermore, tendencies were found regarding the subjective improvement of symptoms (P = .075) and two subscales of the EORTC-QLQ-C30 questionnaire: pain (P = .054) and dyspnea (P = .054). The results for the SMT group were superior regarding the tendon reflexes, and a tendency regarding the subjective report of symptoms, while WBV was superior regarding pain. SMT and WBV behold a large potential to reduce CIPN-related symptoms and can be considered feasible and safe for patients with CIPN (compliance 97.5%, no adverse events).Registration: DRKS00013027.

Nonoperative treatment of muscle injuries - recommendations from the GOTS expert meeting.

BACKGROUND: Muscle injuries are some of the most common injuries in sports; they have a high recurrence rate and can result in the loss of ability to participate in training or competition. In clinical practice, a wide variety of treatment strategies are commonly applied. However, a limited amount of evidence-based data exists, and most therapeutic approaches are solely based on "best practice". Thus, there is a need for consensus to provide strategies and recommendations for the treatment of muscle injuries. METHODS: The 2016 GOTS Expert Meeting, initiated by the German-Austrian-Swiss Society for Orthopaedic Traumatologic Sports Medicine (GOTS), focused on the topic of muscle and tendon injuries and was held in Spreewald/Berlin, Germany. The committee was composed of twenty-two medical specialists. Nine of them were delegated to a subcommittee focusing on the nonoperative treatment of muscle injuries. The recommendations and statements that were developed were reviewed by the entire consensus committee and voted on by the members. RESULTS: The committee reached a consensus on the utility and effectiveness of the management of muscle injuries. MAIN RESULTS: the "PRICE" principle to target the first inflammatory response is one of the most relevant steps in the treatment of muscle injuries. Haematoma aspiration may be considered in the early stages after injury. There is presently no clear evidence that intramuscular injections are of use in the treatment of muscle injuries. The ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) should be regarded critically because there is currently no hard evidence to support their use, although they are appropriate in exceptional cases. CONCLUSIONS: The present work provides a structured overview of the various nonoperative treatment strategies of muscle injuries and evaluates their effectiveness with respect to the existing scientific evidence and clinical expertise in the context of basic science on the healing process of muscle injuries. The committee agreed that there is a compelling need for further studies, including high-quality randomized investigations to completely evaluate the effectiveness of the existing therapeutic approaches. The given recommendations may be updated and adjusted as further evidence will be generated.

Downregulation of the α1- and ß1-subunit of sGC in Arterial Smooth Muscle Cells of OPSCC Is HPV-Independent.

The nitric oxide (NO)-sensitive soluble guanylyl cyclase (sGC) is a heterodimeric enzyme with an α and ß subunit. NO binds to heme of the ß1-subunit of sGC, activates the enzyme in the reduced heme iron state in vascular smooth muscle cells (VSMCs), and generates cGMP-inducing vasodilatation and suppression of VSMC proliferation. In the complex tumor milieu with higher levels of reactive oxygen species (ROS), sGC heme iron may become oxidized and insensitive to NO. To change sGC from an NO-insensitive to NO-sensitive state or NO-independent manner, protein expression of sGC in VSMC is required. Whether sGCα1ß1 exists at the protein level in arterial VSMCs of oropharyngeal squamous cell carcinoma (OPSCC) is unknown. In addition, whether differences in the genetic profile between human papillomavirus (HPV)-positive and HPV-negative OPSCC contributes to the regulation of sGCα1ß1 is unclear. Therefore, we compared the effects of HPV-positive and HPV-negative OPSCC on the expression of sGCα1ß1 in arterial VSMCs from tumor-free and tumor-containing regions of human tissue sections using quantitative immunohistochemistry. In comparison to the tumor-free region, we found a decrease in expression of both α1- and ß1-subunits in the arterial VSMC layer of the tumor-containing areas. The OPSCC-induced significant downregulation of the α1- and ß1-subunits of sGC in arterial VSMC was HPV-independent. We conclude that the response of sGC to NO in tumor arterial VSMCs may be impaired by oxidation of the heme of the ß1-subunit, and thus, α1- and ß1-subunits of sGC could be targeted to degradation under oxidative stress in OPSCC in an HPV-independent manner. The degradation of sGCα1ß1 in VSMCs may result in increased proliferation of VSMCs, promoting tumor arteriogenesis in OPSCC. This can be interrupted by preserving the active heterodimer sGCα1ß1 in arterial VSMCs.

The effects of exercise intensity and post-exercise recovery time on cortical activation as revealed by EEG alpha peak frequency.

Acute physical exercise (APE) induces an increase in the individual alpha peak frequency (iAPF), a cortical parameter associated with neural information processing speed. The aim of this study was to further scrutinize the influence of different APE intensities on post-exercise iAPF as well as its time course after exercise cessation. 95 healthy young (18-35 years) subjects participated in two randomized controlled experiments (EX1 and EX2). In EX1, all participants completed a graded exercise test (GXT) until exhaustion and were randomly allocated into different delay groups (immediately 0, 30, 60 and 90 min after GXT). The iAPF was determined before, immediately after as well as after the group-specific delay following the GXT. In EX2, participants exercised for 35 min at either 45-50%, 65-70% or 85-90% of their maximum heart rate (HRmax). The iAPF was determined before, immediately after as well as 20 min after exercise cessation. In EX1, the iAPF was significantly increased immediately after the GXT in all groups. This effect was not any more detectable after 30 min following exercise cessation. In EX2, a significant increase of the iAPF was found only after high-intensity (85-90% HRmax) exercise. The results indicate intense or exhaustive physical exercise is required to induce a transient increase in the iAPF that persists about 30 min following exercise cessation. Based on these findings, further research will have to scrutinize the behavioral implications associated with iAPF modulations following exercise.

Exercise during short-term exposure to hypoxia or hyperoxia - novel treatment strategies for type 2 diabetic patients?!

Both hypoxia (decreased oxygen availability) and hyperoxia (increased oxygen availability) have been shown to alter exercise adaptations in healthy subjects. This review aims to clarify the possible benefits of exercise during short-term exposure to hypoxia or hyperoxia for patients with type 2 diabetes mellitus (T2DM). There is evidence that exercise during short-term exposure to hypoxia can acutely increase skeletal muscle glucose uptake more than exercise in normoxia, and that post-exercise insulin sensitivity in T2DM patients is more increased when exercise is performed under hypoxic conditions. Furthermore, interventional studies show that glycemic control can be improved through regular physical exercise in short-term hypoxia at a lower workload than in normoxia, and that exercise training in short-term hypoxia can contribute to increased weight loss in overweight/obese (insulin-resistant) subjects. While numerous studies involving healthy subjects report that regular exercise in hypoxia can increase vascular health (skeletal muscle capillarization and vascular dilator function) to a higher extent than exercise training in normoxia, there is no convincing evidence yet that hypoxia has such additive effects in T2DM patients in the long term. Some studies indicate that the use of hyperoxia during exercise can decrease lactate concentrations and subjective ratings of perceived exertion. Thus, there are interesting starting points for future studies to further evaluate possible beneficial effects of exercise in short-term hypoxia or hyperoxia at different oxygen concentrations and exposure durations. In general, exposure to hypoxia/hyperoxia should be considered with caution. Possible health risks-especially for T2DM patients-are also analyzed in this review.

[Effects of a Four-Week Rehabilitation Program on Motor Performance, Quality of Life and Fatigue in Childhood Cancer Patients and Healthy Siblings]. / Einfluss einer vierwöchigen familienorientierten Rehabilitation auf die motorische Leistungsfähigkeit, Lebensqualität und Fatigue bei krebskranken Kindern und gesunden Geschwistern.

Aim In Germany all childhood cancer patients and their families are offered the opportunity to participate in a four-week, family-oriented, inpatient rehabilitation program in order to facilitate (re-)integration into everyday life. The aim of this study is to evaluate the effect of this rehabilitation program on motor performance, quality of life (QoL) and fatigue. Methods Motor performance, QoL and fatigue were assessed in 22 childhood cancer patients and 20 healthy siblings at the beginning (t1) and the end (t2) of the four-week rehabilitation program, as well as 6 months later (t3). Results At t1 significant differences between groups were found in motor performance and physical well-being. Improvements in motor performance, QoL and fatigue were found in both groups. Conclusion Different preconditions must be considered. Childhood cancer patients as well as healthy siblings benefit from a family-oriented rehabilitation program.

Associations between aerobic exercise levels and physical and mental health outcomes in men with bone metastatic prostate cancer: a cross-sectional investigation.

Cancer patients with bone metastases have previously been excluded from participation in physical activity programmes due to concerns of skeletal fractures. Our aim was to provide initial information on the association between physical activity levels and physical and mental health outcomes in prostate cancer patients with bone metastases. Between 2012 and 2015, 55 prostate cancer patients (mean age 69.7 ± 8.3; BMI 28.6 ± 4.0) with bone metastases (58.2% >2 regions affected) undertook assessments for self-reported physical activity, physical and mental health outcomes (SF-36), objective physical performance measures and body composition by DXA. Sixteen men (29%) met the current aerobic exercise guidelines for cancer survivors, while 39 (71%) reported lower aerobic exercise levels. Men not meeting aerobic exercise guidelines had lower physical functioning (p = .004), role functioning (physical and emotional) (p < .05), general health scores (p = .014) as well all lower measures of physical performance (p < .05). Lower levels of aerobic exercise are associated with reduced physical and mental health outcomes in prostate cancer patients with bone metastases. While previous research has focused primarily in those with non-metastatic disease, our initial results suggest that higher levels of aerobic exercise may preserve physical and mental health outcomes in prostate cancer patients with bone metastases. Clinical Trial Registry: Trial Registration: ACTRN12611001158954.

Impact of aerobic exercise training during chemotherapy on cancer related cognitive impairments in patients suffering from acute myeloid leukemia or myelodysplastic syndrome - Study protocol of a randomized placebo-controlled trial.

Cancer related cognitive impairments (CRCI) are frequently reported by patients prior to, during and after medical treatment. Although this cognitive decline severely affects patients' quality of life, little is known about effective treatments. Exercise programs represent a promising supportive strategy in this field. However, evidence is sparse and existing studies display methodological limitations. In the planned study, 83 men and women newly diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) will be randomized into one of three treatment groups. During 4weeks of induction chemotherapy with Anthracycline and Cytarabin patients allocated to exercise group will cycle 3×/week for 30min at moderate to vigorous intensity on an ergometer. Patients allocated to placebo group will receive a supervised myofascial release training (3×/week, approx. 30min) and patients at control group will get usual care. As primary endpoints a cognitive test battery will be conducted measuring performances depending on verbal/spatial memory and executive functioning. Secondary endpoints will be self-perceived cognitive functioning, as well as neurotrophic and inflammatory serum markers. All assessments will be conducted immediately after hospitalization and before chemotherapy is commenced, immediately before discharge of hospital after 4-5weeks as well as before continuing medical treatment 3-4weeks after discharge. This will be the first study investigating the impact of an aerobic exercise training on CRCI in AML/MDS patients. We hope that the study design and the state-of-the-art assessments will help to increase knowledge about CRCI in general and exercise as potential treatment option in this under investigated population.

Effects of Wearing Compression Stockings on the Physical Performance of T2DM Men with MetS.

Metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are associated with macro- and microcirculatory complications that reduce physical performance. Wearing compression garments to potentially optimize hemodynamics has been discussed. This study investigates the effects of wearing compression stockings on physical performance-related variables in type 2 diabetic men with metabolic syndrome (n=9, 57±12 years, BMI: 36±4 kg/m(2)). Participants served as their own controls in a randomized 3*3 crossover study wearing below-knee stockings with either compression (24 or 30 mmHg ankle pressure) or no compression. Venous pooling and lower limb oxygenation profiles were determined with near-infrared spectroscopy and arterial oxygen saturation was determined using a pulse oxymeter. Measurements were performed in the supine lying position, during standing, following 10 tiptoe exercises and after submaximal intensity cycling. In addition, lactate and erythrocyte deformability were analyzed in capillary blood pre- and post-exercise. Erythrocyte deformability was analyzed using a laser-assisted optical rotational red cell analyzer. No significant differences in any variables when wearing different compression or regular stockings were evident at any point of measurement. This study did not reveal any beneficial effects of wearing compression stockings at rest and during acute bouts of moderately intense exercise in this particular patient group.

Endurance training alters enzymatic and rheological properties of red blood cells (RBC) in type 2 diabetic men during in vivo RBC aging.

This study examines the effects of endurance training on red blood cells (RBC) in seventeen non-insulin-dependent type 2 diabetic men with a special focus on in vivo RBC aging. Venous blood was collected pre- and post-training at rest. RBC from whole blood and RBC separated according to cell age by density-gradient centrifugation were analyzed. RBC deformability was measured by ektacytometry. Immunohistochemical staining was performed to quantify the RBC-nitric oxide (NO) synthase activation (RBC-NOSSer1177) because RBC-NOS-produced NO can contribute to increased RBC deformability. The proportion of "young" RBC was significantly higher post-training. RBC deformability of all RBC (RBC of all ages) remained unaltered post-training. During RBC aging, RBC deformability decreased in both pre- and post-training. However, the training significantly increased RBC deformability in "young" and reduced their deformability in aging RBC. RBC-NOS activation remained unaltered in all RBC post-training. It tendentially increased in aging RBC pre-training, but did not change during aging post-training. The training significantly reduced RBC-NOS activation in "old" RBC. Endurance training may improve the RBC system (higher amount of "young" RBC which are more deformable). It remains speculative whether changes in older RBC (reduced RBC-NOS activation and deformability) could lead to more rapid elimination of aged RBC.

Acute effects of superimposed electromyostimulation during cycling on myokines and markers of muscle damage.

OBJECTIVES: The purpose of the present study was to evaluate the effects of superimposed electromyostimulation (E) during cycling on myokines and markers of muscle damage, as E might be a useful tool to induce a high local stimulus to skeletal muscle during endurance training without performing high external workloads. METHODS: 13 subjects participated in three experimental trials each lasting 60 min in a randomized order. 1) Cycling (C), 2) Cycling with superimposed E (C+E) and 3) E. Interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), creatine kinase (CK) and myoglobin were determined before (pre) and 0', 30', 60', 240' and 24h after each intervention. RESULTS: Only C+E caused significant increases in levels of CK and myoglobin. BDNF and IL-6 significantly increased after C and C+E, however increases for IL-6 were significantly higher after C+E compared to C. CONCLUSION: The present study showed that superimposed E during cycling might be a useful tool to induce a high local stimulus to skeletal muscle even when performing low to moderate external workloads. This effect might be due the activation of additional muscle fibers and mild eccentric work due to the concomitant activation of agonist and antagonist. However the higher load to skeletal muscle has to be taken into account.

Physical exercise and epigenetic adaptations of the cardiovascular system.

During the last decade, epigenetics became one of the fastest growing research fields in numerous clinical and basic science disciplines. Evidence suggests that chromatin modifications (e.g., histone modifications and DNA methylation) as well as the expression of micro-RNA molecules play a crucial role in the pathogenesis of several cardiovascular diseases. On the one hand, they are involved in the development of general risk factors like chronic inflammation, but on the other hand, epigenetic modifications are conducive to smooth muscle cell, cardiomyocyte, and endothelial progenitor cell proliferation/differentiation as well as to extracellular matrix processing and endothelial function (e.g., endothelial nitric oxide synthase regulation). Therefore, epigenetic medical drugs have gained increased attention and provided the first promising results in the context of cardiovascular malignancies. Beside other lifestyle factors, physical activity and sports essentially contribute to cardiovascular health and regeneration. In this review we focus on recent research proposing physical activity as a potent epigenetic regulator that has the potential to counteract pathophysiological alterations in almost all the aforementioned cardiovascular cells and tissues. As with epigenetic medical drugs, more knowledge about the molecular mechanisms and dose-response relationships of exercise is needed to optimize the outcome of preventive and rehabilitative exercise programs and recommendations.

Exercise-induced Natural Killer Cell Activation is Driven by Epigenetic Modifications.

Exercise has been proven to reduce the risk and progression of various diseases, such as cancer, diabetes and neurodegenerative disorders. Increasing evidence suggests that exercise affects the cytokine profile and changes distribution and function of tumor-competitive immune cells. Initial studies have shown that different exercise interventions are associated with epigenetic modifications in different tissues and cell types, such as muscle, fat, brain and blood. The present investigation examines the effect of an intense endurance run (half marathon) on global epigenetic modifications in natural killer (NK) cells in 14 cancer patients compared to 14 healthy controls. We were able to show that histone acetylation and NKG2D expression, a functional NK cell marker, were elevated for at least 24 h after the run. Thus, this is the first study to present a potential mechanism of how exercise may impact NK cell activity on the subcellular level. Further studies should focus on epigenetic mechanisms and dose-dependent effects of exercise.

Endurance training alters skeletal muscle MCT contents in T2DM men.

Patients suffering from type 2 diabetes mellitus (T2DM) often exhibit chronic elevated lactate levels which can promote peripheral insulin resistance by disturbing skeletal muscle insulin-signaling. Monocarboxylate transporter (MCT) proteins transfer lactate molecules through cellular membranes. MCT-1 and MCT-4 are the main protein isoforms expressed in human skeletal muscle, with MCT-1 showing a higher affinity (lower Km) for lactate than MCT-4. T2DM patients have reduced membranous MCT-1 proteins. Consequently, the lactate transport between muscle cells and the circulation as well as within an intracellular lactate shuttle, involving mitochondria (where lactate can be further metabolized), can be negatively affected. This study investigates whether moderate cycling endurance training (3 times per week for 3 months) can change skele-tal muscle MCT contents in T2DM men (n=8, years=56±9, body mass index (BMI)=32±4 kg/m(2)). Protein content analyses (immuno-histochemical stainings) were performed in bio-psies taken from the vastus lateralis muscle. Intracellular MCT-1 proteins were up-regulated (relative increase+89%), while intracellular MCT-4 contents were down-regulated (relative decrease - 41%) following endurance training. Sarcolemmal MCT-1 and MCT-4 did not change. The question of whether the training-induced up-regulation of intracellular MCT-1 leads to an improved lactate transport (and clearance) in T2DM patients requires further research.