Living Lab Data of Patient Needs and Expectations for eHealth-Based Cardiac Rehabilitation in Germany and Spain From the TIMELY Study: Cross-Sectional Analysis.

BACKGROUND: The use of eHealth technology in cardiac rehabilitation (CR) is a promising approach to enhance patient outcomes since adherence to healthy lifestyles and risk factor management during phase III CR maintenance is often poorly supported. However, patients' needs and expectations have not been extensively analyzed to inform the design of such eHealth solutions. OBJECTIVE: The goal of this study was to provide a detailed patient perspective on the most important functionalities to include in an eHealth solution to assist them in phase III CR maintenance. METHODS: A guided survey as part of a Living Lab approach was conducted in Germany (n=49) and Spain (n=30) involving women (16/79, 20%) and men (63/79, 80%) with coronary artery disease (mean age 57 years, SD 9 years) participating in a structured center-based CR program. The survey covered patients' perceived importance of different CR components in general, current usage of technology/technical devices, and helpfulness of the potential features of eHealth in CR. Questionnaires were used to identify personality traits (psychological flexibility, optimism/pessimism, positive/negative affect), potentially predisposing patients to acceptance of an app/monitoring devices. RESULTS: All the patients in this study owned a smartphone, while 30%-40% used smartwatches and fitness trackers. Patients expressed the need for an eHealth platform that is user-friendly, personalized, and easily accessible, and 71% (56/79) of the patients believed that technology could help them to maintain health goals after CR. Among the offered components, support for regular physical exercise, including updated schedules and progress documentation, was rated the highest. In addition, patients rated the availability of information on diagnosis, current medication, test results, and risk scores as (very) useful. Of note, for each item, except smoking cessation, 35%-50% of the patients indicated a high need for support to achieve their long-term health goals, suggesting the need for individualized care. No major differences were detected between Spanish and German patients (all P>.05) and only younger age (P=.03) but not sex, education level, or personality traits (all P>.05) were associated with the acceptance of eHealth components. CONCLUSIONS: The patient perspectives collected in this study indicate high acceptance of personalized user-friendly eHealth platforms with remote monitoring to improve adherence to healthy lifestyles among patients with coronary artery disease during phase III CR maintenance. The identified patient needs comprise support in physical exercise, including regular updates on personalized training recommendations. Availability of diagnoses, laboratory results, and medications, as part of a mobile electronic health record were also rated as very useful. TRIAL REGISTRATION: ClinicalTrials.gov NCT05461729; https://clinicaltrials.gov/study/NCT05461729.

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.

Altered tissue oxygenation in patients with post COVID-19 syndrome.

BACKGROUND: Post COVID-19 syndrome (PCS) is a complex condition with partly substantial impact on patients' social and professional life and overall life quality. Currently, the underlying cause(s) of PCS are unknown. Since PCS-specific symptoms could be associated with systemic alterations in tissue oxygen supply, we aimed to investigate changes in tissue oxygenation in patients with PCS. METHODS: A case-control study including 30 PCS patients (66.6 % males, 48.6 ± 11.2 years, mean time after (first) acute infection: 324 days), 16 cardiologic patients (CVD) (65.5 % males, 56.7 ± 6.3 years) and 11 young healthy controls (55 % males, 28.5 ± 7.4 years) was conducted. Near infrared spectroscopy (NIRS) was used to assess changes in tissue oxygenation during an arterial occlusion protocol on the non-dominant forearm (brachioradialis, 760/850 nm, 5 Hz). The protocol included 10-min rest, a 2-min baseline measurement followed by a 3-min ischemic period (upper-arm cuff, 50 mmHg above resting systolic blood pressure) and a 3-min reoxygenation period. PCS patients were grouped by presence of arterial hypertension and elevated BMI to assess the impact of risk factors. RESULTS: No differences in mean tissue oxygenation in the pre-occlusion phase existed between groups (p ≥ 0.566). During ischemia, comparisons of linear regressions slopes revealed slower oxygen desaturation for PCS patients (-0.064 %/s) compared to CVD patients (-0.08 %/s) and healthy subjects (-0.145 %/s) (p < 0.001). After cuff release, slowest speed for reoxygenation was detected in PCS patients at 0.84 %/s compared to CVD patients (1.04 %/s) and healthy controls (CG: 2.07 %/s) (p < 0.001). The differences between PCS patients and CVD patients during ischemia remained significant also after correction for risk factors. Analyses of complications during acute infection, persistence of PCS symptoms (time after acute infection), or PCS severity (number of lead symptoms) as confounding factors did not reveal a significant effect. CONCLUSIONS: This study provides evidence that the rate of tissue oxygen consumption is persistently altered in PCS and that PCS patients show an even slower decline in tissue oxygenation during occlusion than CVD patients. Our observations may at least partly explain PCS-specific symptoms such as physical impairment and fatigue.

miR-486 attenuates cardiac ischemia/reperfusion injury and mediates the beneficial effect of exercise for myocardial protection.

Exercise and its regulated molecules have myocardial protective effects against cardiac ischemia/reperfusion (I/R) injury. The muscle-enriched miR-486 was previously identified to be upregulated in the exercised heart, which prompted us to investigate the functional roles of miR-486 in cardiac I/R injury and to further explore its potential in contributing to exercise-induced protection against I/R injury. Our data showed that miR-486 was significantly downregulated in the heart upon cardiac I/R injury. Both preventive and therapeutic interventions of adeno-associated virus 9 (AAV9)-mediated miR-486 overexpression could reduce cardiac I/R injury. Using AAV9 expressing miR-486 with a cTnT promoter, we further demonstrated that cardiac muscle cell-targeted miR-486 overexpression was also sufficient to protect against cardiac I/R injury. Consistently, miR-486 was downregulated in oxygen-glucose deprivation/reperfusion (OGDR)-stressed cardiomyocytes, while upregulating miR-486 inhibited cardiomyocyte apoptosis through PTEN and FoxO1 inhibition and AKT/mTOR activation. Finally, we observed that miR-486 was necessary for exercise-induced protection against cardiac I/R injury. In conclusion, miR-486 is protective against cardiac I/R injury and myocardial apoptosis through targeting of PTEN and FoxO1 and activation of the AKT/mTOR pathway, and mediates the beneficial effect of exercise for myocardial protection. Increasing miR-486 might be a promising therapeutic strategy for myocardial protection.

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.

Cardiac endurance training alters plasma profiles of circular RNA MBOAT2.

Marathon running is an extreme physical activity, which determines cardiopulmonary adaption of athletes. Circular RNAs (circRNAs) as potential biomarkers in the blood stream have so far not been tested after such strenuous activities. In silico approaches were performed to identify the potential candidate circRNA MBOAT2. Next, we demonstrated high stability and conservation of circRNA MBOAT2 as well as its abundancy in human plasma. In addition to Sanger sequencing of the circRNA specific head-to-tail junction, or back-splice site, we established a synthetic plasmid standard which allowed exact copy number calculations of circRNA MBOAT2. We then analyzed plasmatic circRNA MBOAT2 and observed a significantly lower level 24 h after the marathon. Such alterations were correlated to physical exercise parameters confirming the role of circRNA MBOAT2 as a promising noncoding RNA biomarker detecting cardiopulmonary adaption.NEW & NOTEWORTHY In brief, we herein report a timeline of circulating circular RNA (circRNA) MBOAT2 in a cohort of marathon runners. Time-course analysis of plasmatic circRNA MBOAT2 demonstrated a significantly lowered level 24 h after the marathon. Abundancy of circRNA was correlated to physical exercise parameters highlighting the role of circRNA MBOAT2 as a valuable noncoding RNA biomarker detecting and following up cardiopulmonary adaption.

Combined effects of moderate exercise and short-term fasting on markers of immune function in healthy human subjects.

This study aimed to investigate the effects of a short-term (36 h) fasting period combined with an acute bout of exercise on markers of immune function and inflammation in healthy human subjects. Fourteen moderately trained male subjects (aged 19-39 yr) participated in a 36-h fasting trial (FA-T), followed by an acute bout of moderate exercise (60% V̇o2max). After 1 wk, the same subjects, as their own control, participated in a nonfasting trial (NFA-T) in which they performed an exercise trial of the same duration and intensity. Blood samples were taken before, immediately after, and 1 h after each exercise bout and analyzed for several immunological and metabolic markers. At baseline, fasting subjects showed lower levels of T cell apoptosis, lymphocyte-proliferative responses, IL-6, monocyte chemoattractant protein-1 (MCP-1), insulin, and leptin (P < 0.05) as well as higher levels of neutrophil oxidative burst and thiobarbituric acid reactive substances (TBARS) than those in the NFA-T (P < 0.05). After the exercise protocol, fasted subjects revealed higher T cell apoptosis, neutrophil oxidative burst, TBARS, TNFα, and MCP-1 levels as well as lower levels of lymphocyte-proliferative response, IL-6, insulin, and leptin than those in the NFA-T (P < 0.05). Short-term fasting aggravates perturbations in markers of immune function, and inflammation was induced by an acute moderate-intensity exercise protocol.

Aerobic endurance training status affects lymphocyte apoptosis sensitivity by induction of molecular genetic adaptations.

Apoptosis is a genetically regulated form of programmed cell death which promotes the elimination of potentially detrimental immune cells. However, exercise-associated apoptosis is thought to induce a temporarily decline of the adaptive immune competence in the early post-exercise period. The purpose of the present study was to investigate if the aerobic endurance training status affects the sensitivity of human peripheral blood lymphocytes towards different types of apoptosis inducers and secondly, if this is mediated by the modulation of apoptosis-associated proteins and microRNAs. Collected at resting conditions, isolated lymphocytes of endurance trained athletes (ET) and healthy untrained subjects were either exposed to phytohemagglutinin-L (PHA-L), hydrogen peroxide (H2O2), or dexamethasone (DEX) as apoptosis inducer. Results revealed no significant differences between ET and UT in terms of lymphocyte apoptosis immediately following isolation as determined by flow cytometry using annexin V staining. After 24 h of ex vivo cultivation, lymphocytes of ET showed a reduced sensitivity to PHA-L-induced lymphocyte apoptosis which was accompanied by a noticeably up-regulation of the prominent apoptosis inhibitor genes X-linked inhibitor of apoptosis (XIAP) and Cyclin dependent kinase inhibitor 1B (CDKN1B) as analyzed by quantitative real-time PCR. Moreover, a trend was observed for the suppression of the corresponding pro-apoptotic miR-221. Lymphocyte apoptosis in control, H2O2 and DEX treated cells was not affected by aerobic endurance training status. However, distinct molecular signatures could be identified in un-treated control samples characterized by a counterbalanced modulation of pro- and anti-apoptotic mediators in ET. The results of the current study suggest that lymphocytes adapt to repetitive endurance exercise training by promoting lymphocyte homeostasis and increasing their resistance to apoptosis. This could be based on an up-regulation of anti-apoptotic proteins and a reduction in pro-apoptotic microRNAs which together tightly regulate the genetically defined apoptotic pathways governed by the type of apoptosis stimuli. Thus, the lymphocytes of endurance-trained athletes may be primed to counteract the transient immune suppression post-exercise.

Exercise training reverses inflammation and muscle wasting after tobacco smoke exposure.

Long-term cigarette smoking induces inflammatory processes in the pulmonary system that are suggested to "spill over" into systemic inflammation. Regular exercise has been shown to have anti-inflammatory properties. The aim of the study was to investigate the effects of therapeutic exercise on inflammation and muscle wasting in smoke-exposed mice. C57BL/6J mice ( n = 30) were separated into three groups to receive either 1) no specific treatment (control group), 2) 8-mo exposure to cigarette smoke [smoke-exposed (SE) group], or 3) 8 mo of cigarette smoke combined with exercise training during the last 2 mo (SEex group). The inflammatory status was analyzed by quantifying levels of various plasma proteins using multiplex ELISA and detection of lymphocyte surface markers by flow cytometry. Muscle tissue was analyzed by histological techniques and measurements of RNA/protein expression. SE led to decreased maximal O2 uptake (V̇o2max) and maximal running speed ( Vmax), which was reversed by exercise ( P < 0.05). Expression of ICAM-1, VCAM-1, and CD62L on T cells increased and was reversed by exercise ( P < 0.05). Similarly, SE induced an increase of various inflammatory cytokines, which were downregulated by exercise. In muscle, exercise improved the structure, oxidative capacity, and metabolism by reducing ubiquitin proteasome system activation, stimulating insulin-like growth factor 1 expression, and the SE-induced inhibition of mammalian target of rapamycin signaling pathway ( P < 0.05). Exercise training reverses smoke-induced decline in exercise capacity, systemic inflammation, and muscle wasting by addressing immune-regulating, anabolic, and metabolic pathways.

Low-to-moderate intensity aerobic exercise training modulates irritable bowel syndrome through antioxidative and inflammatory mechanisms in women: Results of a randomized controlled trial.

Our aim was to explore the putative beneficial effects of low-to-moderate intensity exercise training program in patients with irritable bowel syndrome (IBS). This study evaluated the changes in blood oxidative stress status, inflammatory biomarkers and IBS severity symptoms following 24 weeks of moderate aerobic exercise in sedentary IBS patients. A total of 109 female volunteers (aged 18-41 yrs) who fulfilled Rome III criteria for the diagnosis of IBS were screened and 60 were randomized to exercise (EX, n = 30) and non-exercise (NON-EX, n = 30) groups. Exercise intervention favorably attenuated inflammation as indicated by plasma cytokines (IL-1ß, IL-6, IL-8, IL-10 and TNF-α), adenosine deaminase, oxidative stress (XO, MDA and NO) and enhanced antioxidants (SOD, CAT and GSH-Px) (P < .05), and these alterations correlate with promising improvements in IBS symptoms (P < .05). Taken together, low-to-moderate intensity exercise training program attenuates symptoms in IBS. Symptom improvement was associated with a reversal of the ratio of anti- to pro-inflammatory cytokines as well as facilitating blood redox homeostasis, suggesting an immune- and redox modulating function for exercise training.

Probing depth is an independent risk factor for HbA1c levels in diabetic patients under physical training: a cross-sectional pilot-study.

BACKGROUND: This cross-sectional study investigates the potential association between active periodontal disease and high HbA1c levels in type-2-diabetes mellitus subjects under physical training. METHODS: Women and men with a diagnosis of non-insulin-dependent diabetes mellitus and ongoing physical and an ongoing exercise program were included. Periodontal conditions were assessed according to the CDC-AAP case definitions. Venous blood samples were collected for the quantitative analysis of HbA1c. Associations between the variables were examined with univariate and multivariate regression models. RESULTS: Forty-four subjects with a mean age of 63.4 ± 7.0 years were examined. Twenty-nine subjects had no periodontitis, 11 had a moderate and 4 had a severe form of periodontal disease. High fasting serum glucose (p < 0.0001), high BMI scores (p = 0.001), low diastolic blood pressure (p = 0.030) and high probing depth (p = 0.036) were significantly associated with high HbA1c levels. CONCLUSIONS: Within the limitations of this study HbA1c levels are positively associated with high probing pocket depth in patients with non-insulin-dependent diabetes mellitus under physical exercise training. Control and management of active periodontal diseases in non-insulin-dependent patients with diabetes mellitus is reasonable in order to maximize therapeutic outcome of lifestyle interventions.

Forced exercise-induced osteoarthritis is attenuated in mice lacking the small leucine-rich proteoglycan decorin.

OBJECTIVE: Interterritorial regions of articular cartilage matrix are rich in decorin, a small leucine-rich proteoglycan and important structural protein, also involved in many signalling events. Decorin sequesters transforming growth factor ß (TGFß), thereby regulating its activity. Here, we analysed whether increased bioavailability of TGFß in decorin-deficient (Dcn-/-) cartilage leads to changes in biomechanical properties and resistance to osteoarthritis (OA). METHODS: Unchallenged knee cartilage was analysed by atomic force microscopy (AFM) and immunohistochemistry. Active transforming growth factor ß-1 (TGFß1) content within cultured chondrocyte supernatants was measured by ELISA. Quantitative real-time (RT)-PCR was used to analyse mRNA expression of glycosaminoglycan (GAG)-modifying enzymes in C28/I2 cells following TGFß1 treatment. In addition, OA was induced in Dcn-/- and wild-type (WT) mice via forced exercise on a treadmill. RESULTS: AFM analysis revealed a strikingly higher compressive stiffness in Dcn-/- than in WT cartilage. This was accompanied by increased negative charge and enhanced sulfation of GAG chains, but not by alterations in the levels of collagens or proteoglycan core proteins. In addition, decorin-deficient chondrocytes were shown to release more active TGFß1. Increased TGFß signalling led to enhanced Chst11 sulfotransferase expression inducing an increased negative charge density of cartilage matrix. These negative charges might attract more water resulting in augmented compressive stiffness of the tissue. Therefore, decorin-deficient mice developed significantly less OA after forced exercise than WT mice. CONCLUSIONS: Our study demonstrates that the disruption of decorin-restricted TGFß signalling leads to higher stiffness of articular cartilage matrix, rendering joints more resistant to OA. Therefore, the loss of an important structural component can improve cartilage homeostasis.

Consensus Statement Immunonutrition and Exercise.

In this consensus statement on immunonutrition and exercise, a panel of knowledgeable contributors from across the globe provides a consensus of updated science, including the background, the aspects for which a consensus actually exists, the controversies and, when possible, suggested directions for future research.

Effects of Traumeel (Tr14) on recovery and inflammatory immune response after repeated bouts of exercise: a double-blind RCT.

PURPOSE: The purpose of this double-blind, randomized, placebo-controlled clinical trial was to investigate the effects of the natural combination medicine Traumeel (Tr14) consisting of 14 diluted biological and mineral components on the inflammatory immune response and recovery up to 72 h after repetitive bouts of bicycle tests. METHODS: Antigen-stimulated IL-1ra and IL-6 were defined as primary outcome measures. Moreover, various immunological and serum muscle damage markers were investigated. The evaluation was performed using the score of the area under the curve with respect to increase (AUCi) for 24 and 72 h after the second exercise test (EX2). RESULTS: The Tr14 group indicated a lower decrease of lymphocytes by tendency (p = 0.06) and a lower activation of lymphocyte activation markers (CD62L absolute: p = 0.04; CD69: p = 0.01 and CD69 absolute: p = 0.05) in the period 24 h after EX2. In addition, the Tr14 group indicated a higher expression of antigen-stimulated CCL3 (p = 0.01), CCL4 (p = 0.07) and serum CCL2 (p = 0.05) in the period 24 h after EX2. There was a tendentially lower decrease of monocytes (p = 0.09) and a lower expression of antigen-stimulated MMP-3 (p = 0.01) in the Tr14 group in the period 72 h after EX2. However, antigen-stimulated IL-1ra and IL-6 showed no group differences. CONCLUSION: In line with the previous results, it was shown that Tr14 attenuates the adaptive immune response partially. Furthermore, the results indicate that Tr14 is able to stimulate the innate immune system via an increased production of pro-inflammatory chemokines. It is speculated that the higher expression of chemokines might play a role in the regeneration and recovery after exercise.

A randomized controlled trial examining the effects of 16 weeks of moderate-to-intensive cycling and honey supplementation on lymphocyte oxidative DNA damage and cytokine changes in male road cyclists.

The aim of this study was to investigate whether honey supplementation (70g, ninety minutes before each training session) attenuates changes in lymphocyte counts, DNA damage, cytokines, antioxidative and peroxidative biomarkers following moderate-to-intensive exercise training in male road cyclists. Healthy nonprofessional cyclists (n=24, aged 17-26years) were randomly assigned to exercise+supplement (EX+S, n=12) and exercise (EX, n=12) groups for an experimental period of 16weeks. Moderate-to-intensive exercise training increased lymphocytes DNA damage, cytokines and peroxidative biomarkers as well as decreased antioxidative biomarkers in the EX group. These changes were significantly attenuated in the EX+S group. Furthermore, for both groups the observed changes in peroxidative and antioxidative biomarkers could be correlated positively and negatively, respectively, with lymphocyte DNA damage and cytokines. Findings suggest that honey attenuates oxidative stress and lymphocyte DNA damage after exercise, activities that are most likely attributable to its high antioxidant capacity.

Effects of Traumeel (Tr14) on Exercise-Induced Muscle Damage Response in Healthy Subjects: A Double-Blind RCT.

The present double-blind, randomized, placebo-controlled clinical trial intended to test whether ingestion of a natural combination medicine (Tr14 tablets) affects serum muscle damage and inflammatory immune response after downhill running. 96 male subjects received Tr14 tablets, which consist of 14 diluted biological and mineral components, or a placebo for 72 h after the exercise test, respectively. Changes in postexercise levels of various serum muscle damage and immunological markers were investigated. The area under the curve with respect to the increase (AUCi) of perceived pain score and creatine kinase (CK) were defined as primary outcome measures. While for CK the p value of the difference between the two groups is borderline, the pain score and muscle strength were not statistically significant. However, a trend towards lower levels of muscle damage (CK, p = 0.05; LDH, p = 0.06) in the Tr14 group was shown. Less pronounced lymphopenia (p = 0.02), a trend towards a lower expression of CD69 count (p = 0.07), and antigen-stimulated ICAM-1 (p = 0.01) were found in the verum group. The Tr14 group showed a tendentially lower increase of neutrophils (p = 0.10), BDNF (p = 0.03), stem cell factor (p = 0.09), and GM-CSF (p = 0.09) to higher levels. The results of the current study indicate that Tr14 seems to limit exercise-induced muscle damage most likely via attenuation of both innate and adaptive immune responses. This study was registered with ClinicalTrials.gov (NCT01912469).

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.

Magnesium and disturbances in carbohydrate metabolism.

Magnesium is actively involved in a number of metabolic reactions as an important co-factor, with special emphasis on carbohydrate metabolism. After a brief overview of the regulation of intra- and extracellular magnesium, the present review first describes the regulatory role of magnesium in important metabolic pathways involved in energy metabolism and glycaemic control. Next the clinical significance of hypomagnesaemic conditions with regard to the management of glucose in prediabetic stages, such as insulin resistance/impaired glucose tolerance and in type 2 diabetes mellitus are characterized. Cross-sectional as well as longitudinal studies suggest that a reduced dietary magnesium intake serves as a risk factor for the incidence of both impaired glucose regulation and type 2 diabetes. Mechanisms that might be responsible for diabetes-associated hypomagnesaemia are discussed. Furthermore, the role of hypomagnesaemia in the development and progression of chronic diabetic complications are addressed. Finally, the available literature on the effects of magnesium supplementation on glycaemic control parameters during prediabetic conditions (preventive approach) as well as type 2 diabetes mellitus (therapeutic approach) are reviewed systematically. There is considerable evidence that chronic magnesium supplementation may delay the progression from impaired glucose regulation to type 2 diabetes; however, the effects of oral magnesium supplementation as an adjunct therapy for type 2 diabetes are quite heterogeneous with respect to the various measures of glycaemic control. The results of this review suggest a requirement for critical consideration of the pros and cons of magnesium replacement therapy, based on variables such as magnesium status, stage of disease and glycaemic control.