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Oral contraceptive pills (OCP) are very popular in female athletes not only for contraceptive effects but also due to the possibility of cycle manipulation. Moreover, it is debatable whether the manipulation of the menstrual cycle has a beneficial effect on exercise performance. Therefore, the aim of this study was to investigate potential differences in knee-extensor and flexor strength performance of first division team sport athletes between phases of the oral contraceptive cycle. Sixteen female handball players (age: 23.3 ± 3.1 years; body mass: 67.0 ± 8.52 kg; body stature: 1.68 ± 0.05 m) using a monophasic OCP participated in strength performance tests, once during OCP consumption (CONS) and once during withdrawal (WITH). Tests were performed on a dynamometer to measure knee-extensor and flexor maximal voluntary isokinetic and isometric torque. Prior to each test, body mass was assessed, and venous blood samples were collected. Wilcoxon signed-rank test and magnitude-based inferences have been conducted to analyze differences between WITH and CONS. Significance was accepted at P < 0.05. No significant differences between oral contraceptive cycle phases of knee-extensor and flexor strength parameters and body mass have been indicated (all at P > 0.05). Follicle-stimulating hormone (FSH) ( P = 0.001) and luteinizing hormone ( P = 0.013) were significantly higher in WITH, whereby estradiol and progesterone showed no significant difference between phases (both at P > 0.05). These results support the notion that knee-extensor and flexor isokinetic and isometric strength performance does not differ between phases of oral contraceptive cycle in well-trained team sport athletes. OCP intake is suggested to cause a stable but downregulated hormone cycle, which has no effect on knee-extensor and flexor strength when comparing oral contraceptive cycle phases. Therefore, manipulation of the female cycle using OCP in order to achieve a higher knee-extensor and flexor strength performance does not seem to be justified; however, it is currently unclear if cycle manipulation might affect other physiological systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Reif, Wessner, Haider, Tschan and Triska.)

This article reports test-retest reliability data of laboratory- and field-based performance tests as well as body composition analyses of younger and older Kosovan adults. In total, 57 healthy young (18-35 years) and 61 older (>60 years) participants took part in two identical test sessions, with a median [25 th - 75 th percentile] of 14 [13-21] days in between. Functional performance tests included 30-s chair stand test (CST), 30-s arm curl test (ACT), six-minutes walking test (6MWT), sit and reach test, timed up and go test (TUG), as well as the assessment of gait speed (GS) at normal and fast pace. Isometric handgrip strength (HGS) was used to estimate strength of the dominant hand. Isokinetic peak torque (PT) and average power (AvgP) for knee extension and flexion were determined at velocities of 60°/s and 120°/s. Body composition assessments included body fat percentage, skeletal muscle mass (SMM) and index (SMI) as well as appendicular skeletal muscle mass (ASMM) and index. Secondary endpoints included self-perceived health status and potential co-morbidities. All performance test outcomes as well as body fat percentage, SMM, ASMM, and self-perceived health were significantly better in young as compared to older participants ( p < 0.001). Improvements from test to retest were observed for CST ( p < 0.001), PT flexion (60°/s: p  = 0.001, 120°/s: p  = 0.041), AvgP flexion (60°/s: p < 0.001, 120°/s: p < 0.001), AvgP extension (120°/s: p  = 0.050), but also for SMM ( p  = 0.021) and SMI ( p  = 0.021). Only for CST and HGS a time x age group interaction was detected ( p < 0.05). Acceptable reliability (ICC > 0.7) was observed for all parameters in both age groups, except for some of the measures from the isokinetic dynamometry, where ICCs were generally lower in older participants, but fell below 0.7 for AvgP flexion at 60°/s (ICC = 0.6) and at 120°/s (ICC = 0.67) as well as for PT flexion at 120°/s (ICC = 0.69). These data's importance lay upon their potential use in epidemiological studies observing muscle strength, peak torque, power, physical performance and body composition over various age groups, either in the same or similar populations, or for comparison to other populations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships, which have or could be perceived to have influenced the work reported in this article., (© 2021 The Author(s).)

Purpose: This study aimed to assess and compare the systemic response of oxygen uptake kinetics and muscle deoxygenation between a 30-min rest protocol and a multivisit protocol on the parameters of the power-duration relationship (i.e., critical power [CP] and W')., Methods: Nine endurance-trained triathletes reported to the laboratory on five occasions: a preliminary graded exercise test and a familiarization, a 30-min single-visit protocol (time trials of 10, 5, and 2 min in that order interspersed with 30 min rest), and a multivisit protocol (time trials of 10, 5, and 2 min in randomized order interspersed by >24 h rest). Heart rate (HR) was recorded continuously, respiratory gases were measured breath by breath, and deoxygenation was recorded at 10 Hz using near-infrared spectroscopy (NIRS) during all tests. Blood lactate (BLa-) concentration was measured before all time trials. Maximal HR (HRmax), oxygen uptake (V˙O2) during the first 2 min (V˙O2onset), mean response time, end-exercise V˙O2 (V˙O2peak), V˙O2 amplitude (amplV˙O2), O2 deficit, NIRS τ, amplitude (amplNIRS), and time delay were assessed. To compare the two protocols and to assess the differences in W' and CP, a paired sample t-test was used as well as a two-way ANOVA to assess the differences between trials and/or protocols, including trial-protocol interactions., Results: No significant differences, and trivial effect sizes, were found for W' and CP between protocols (P = 0.106-0.114, d < 0.01-0.08). Furthermore, no significant differences between protocols were found for all parameters, except for [BLa-]. Significant differences between trials were found for V˙O2ampl, V˙O2onset, NIRS τ, amplNIRS, [BLa-], and HRmax., Conclusion: Results suggest that W' and CP can be determined using the 30-min rest protocol without confounding effects of previous severe exercise compared with the multivisit protocol., (Copyright © 2020 by the American College of Sports Medicine.)

Hamstring injuries remain the most common injury type across many professional sports. Despite a variety of intervention strategies, its incidence in soccer players playing in the UEFA Champions League has increased by 4% per year over the last decade. Test batteries trying to identify potential risk factors have produced inconclusive results. The purpose of the current study was to prospectively record hamstring injuries, to investigate the incidence and characteristics of the injuries, and to identify possible risk factors in elite male soccer players, playing in the Kosovo national premier league. A total of 143 soccer players from 11 teams in Kosovo were recruited. To identify possible prevalent musculoskeletal or medical conditions a widespread health and fitness assessment was performed including isokinetic strength testing, Nordic hamstring strength test, functional tests, and a comprehensive anamnesis surveying previous hamstring injuries. On average 27.9% of the players sustained at least one hamstring injury with three players suffering bilateral strains with the re-injury rate being 23%. Injured players were significantly older and heavier and had a higher body mass index compared to non-injured ones (p < 0.05). There was a lower passing rate in the Nordic hamstring strength test and a higher injury incidence among the previously injured players compared to non-injured ones (p < 0.05). Except for hamstring/quadriceps ratio and relative torque at 60°/sec (p < 0.05) for dominant and non-dominant leg, there were no other significant differences in isokinetic strength regardless of the angular velocity. No differences were observed for functional tests between cohorts. Regression analysis revealed that age, Nordic hamstring strength test, previous injury history, and isokinetic concentric torque at 240°/sec could determine hamstring injuries by 25.9%, with no other significant predicting risk factors. The battery of laboratory and field-based tests performed during preseason to determine performance related skills showed limited diagnostic conclusiveness, making it difficult to detect players at risk for future hamstring injuries., Competing Interests: The authors have declared that no competing interests exist.

With advancing age, the skeletal muscle extracellular matrix (ECM) undergoes fibrotic changes that may lead to increased muscle stiffness, injury susceptibility and strength loss. This study tested the potential of different exercises to counter these changes by stimulating the activity of genes associated with ECM remodeling. Twenty-six healthy men (66.9 ± 3.9 years) were stratified to two of four groups, performing unilateral (i) conventional resistance exercise, (ii) conventional resistance exercise followed by self-myofascial release (CEBR), (iii) eccentric-only exercise (ECC) or (iv) plyometric jumps (PLY). The non-trained leg served as control. Six hours post-exercise, vastus lateralis muscle biopsy samples were analyzed for the expression of genes associated with ECM collagen synthesis (COL1A1), matrix metallopeptidases (collagen degradation; MMPs) and peptidase inhibitors (TIMP1). Significant between-group differences were found for MMP3, MMP15 and TIMP1, with the greatest responses in MMP3 and TIMP1 seen in CEBR and in MMP15 in ECC. MMP9 (3.24-3.81-fold change) and COL1A1 (1.47-2.40-fold change) were increased in CEBR and PLY, although between-group differences were non-significant. The expression of ECM-related genes is exercise-specific, with CEBR and PLY triggering either earlier or stronger remodeling than other stimuli. Training studies will test whether execution of such exercises may help counter age-associated muscle fibrosis.

Skeletal muscle represents the largest body-composition component in humans. In addition to its primary function in the maintenance of upright posture and the production of movement, it also plays important roles in many other physiological processes, including thermogenesis, metabolism and the secretion of peptides for communication with other tissues. Research attempting to unveil these processes has traditionally focused on muscle fibers, i.e., the contractile muscle cells. However, it is a frequently overlooked fact that muscle fibers reside in a three-dimensional scaffolding that consists of various collagens, glycoproteins, proteoglycans, and elastin, and is commonly referred to as extracellular matrix (ECM). While initially believed to be relatively inert, current research reveals the involvement of ECM cells in numerous important physiological processes. In interaction with other cells, such as fibroblasts or cells of the immune system, the ECM regulates muscle development, growth and repair and is essential for effective muscle contraction and force transmission. Since muscle ECM is highly malleable, its texture and, consequently, physiological roles may be affected by physical training and disuse, aging or various diseases, such as diabetes. With the aim to stimulate increased efforts to study this still poorly understood tissue, this narrative review summarizes the current body of knowledge on (i) the composition and structure of the ECM, (ii) molecular pathways involved in ECM remodeling, (iii) the physiological roles of muscle ECM, (iv) dysregulations of ECM with aging and disease as well as (v) the adaptations of muscle ECM to training and disuse., (Copyright © 2020 Csapo, Gumpenberger and Wessner.)

Bioavailability of nutrients is highly diverse and depends on a variety of endogenous and exogenous factors in humans. This data article reports on the plasma response of 10 human subjects (5 females, 5 males) to a single dose of a multivitamin drink within 6h (blood taken after 1, 2, 4, and 6h). Nutrients, which were considered in the assessment, were folate (Radioimmuno Assay), vitamin B12 (Radioimmuno Assay) and resveratrol and its plasma metabolites resveratrol-3- O -glucuronide (R3G), resveratrol-4'- O -glucuronide (R4G), resveratrol-3- O -sulfate (R3S) and resveratrol-3- O -4'- O -disulfate (RD, all HPLC). Biological outcome measures were malondialdehyde (MDA, HPLC) and Ferric Reducing ability potential (FRAP, Microplate reader). Mean plasma concentration increased over time significantly for folate (p < 0.05, maximum concentration (Tmax) after 2h), R3G, R4G, R3S (all p < 0.05, Tmax after 1h), RD (p < 0.05, Tmax after 2h) as well as MDA, which decreased (p < 0.05, Tmax after 2h). No significant change was observed for vitamin B12 and FRAP. Within this mean development, individual changes of participants were highly diverse such as for folate from +42 to +422%, for MDA from -49 to +30% or vitamin B12 from -4 to +33%. For R4G 4 out of 10 subjects showed even no increase in plasma at all. For R4G plasma response ranged from 0 to 36 ng/ml, for R3G from 0 to 53 ng/ml or for R4S from 62 to 265 ng/ml. There was no gender difference regarding the plasma response., (© 2020 The Authors.)

The purpose of this study was to investigate the effect of six months strength training with or without supplementing protein and vitamins, on chromosomal integrity of buccal cells in institutionalized elderly. One hundred seventeen women and men (65-98 years) performed either resistance training (RT), RT combined with a nutritional supplement (RTS) or cognitive training (CT) twice per week for six months. Participants' fitness was measured using the 6 min walking, the chair rise, and the handgrip strength test. Genotoxicity and cytotoxicity parameters were investigated with the Buccal Micronucleus Cytome (BMcyt) assay. Six minutes walking and chair rise performance improved significantly, however, no changes of the parameters of the BMcyt were detected. Age and micronuclei (MN) frequency correlated significantly, for both women (r = 0.597, p = 0.000) and men (r = 0.508, p = 0.000). Squared regressions revealed a significant increase in the MN frequency of buccal cells with age (R 2  = 0.466, p = 0.000). Interestingly and contrary to what was shown in blood lymphocytes, chromosomal damage in buccal cells increases until very old age, which might qualify them as a valid biomarker for aging. Unexpectedly, in this group of institutionalized elderly, resistance training using elastic bands had no effect on chromosomal damage in buccal cells., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Former athletes who continue a regular, performance-oriented training throughout life provide a unique model for studying successful aging. With this in mind, the current study aimed to compare the effects of an acute resistance exercise on proteolytic and myogenic markers in older weightlifters and untrained participants., Methods: Sixteen older men (8 former weightlifters, 8 age-matched untrained controls) with an age of 61.2±8.2 years volunteered to participate in the study. Two days after assessing 1-RM, an acute exercise protocol (3 sets, 70-75% of one-repetition maximum until voluntary fatigue) was applied unilaterally on the dominant leg while the other leg served as control. Three hours after termination of the exercise, skeletal muscle tissue was obtained from m. vastus lateralis of both legs., Results: Acute resistance exercise led to an up-regulation (>1.5-fold) of 14 genes in controls and of 13 genes in weightlifters. The transcription factors FOS and early growth response 1 (EGR1), as well as the E3 protein ligase TRIM63 comprised the most responsive genes to resistance exercise (EGR1:15.7-fold increase, P=0.003, FOS: 36.3-fold increase, P<0.001; TRIM63: 2.9-fold increase, P<0.001). In addition, myostatin levels were decreased in the exercised leg (0.6-fold, P<0.001). FOXO3 gene expression was significantly higher in weightlifters than in untrained controls (1.5-fold, P=0.042)., Conclusions: Trained and untrained older adults respond to an acute bout of resistance exercise in a very similar way irrespective of training status, although some differences exist in FOXO3, potentially reflecting the superior capacity of trained persons in regulating cellular homeostasis.

Background: Institutionalized elderly are at higher risk for micronutrient deficiency. In particular, fat soluble micronutrients, which additionally have antioxidative function, are of interest. The purpose of this secondary investigation of the Vienna Active Ageing Study was to assess and evaluate the plasma status of retinol, alpha- and gamma-tocopherol, alpha- and beta-carotene, lutein, zeaxanthin, beta-cryptoxanthin, and lycopene, as well as vitamin D (25(OH)D) in a cohort of institutionalized elderly. We further determined the effect of six months strength training with or without supplementing (antioxidant) vitamins and protein on the plasma status of these ten micronutrients., Methods: Three groups ( n = 117, age = 83.1 ± 6.1 years)-resistance training (RT), RT combined with protein and vitamin supplementation (RTS), or cognitive training (CT)-performed two guided training sessions per week for six months. Micronutrients were measured with High Performance Liquid Chromatography (HPLC) at baseline and after 6 months of intervention. Physical fitness was assessed by the 6-min-walking, the 30-s chair rise, isokinetic dynamometry, and the handgrip strength tests., Results: At baseline, the plasma status of retinol was satisfactory, for alpha-tocopherol, beta-carotene, and 25(OH)D, the percentage of individuals with an insufficient status was 33%, 73% and 61%/81% (when using 50 nmol/L or 75 nmol/L as threshold levels for 25(OH)D), respectively. Plasma analyses were supported by intake data. Six months of elastic band resistance training with or without protein-vitamin supplementation had no biological impact on the status of fat soluble micronutrients. Even for vitamin D, which was part of the nutritional supplement (additional 20 µg/d), the plasma status did not increase significantly, however it contributed to a lower percentage of elderly below the threshold levels of 50/75 nmol/L (49%/74%)., Conclusions: The findings of the study lead to the strong recommendation for regular physical activity and increased consumption of plant-based foods in institutionalized elderly. When supported by blood analysis, supplementing micronutrients in a moderate range should also be considered.

Implementing sit/stand workstations in sedentary work environments is a common way to reduce sedentary time, but their medium-term effect on cognitive performance is unclear. To address this circumstance, eighteen office workers participated in a two-arm, randomised controlled cross-over trial (ClinicalTrials.gov Identifier: NCT02825303), either working at a traditional (sit) or an interventional (sit/stand) workplace for 23 weeks. Cognitive performance (working speed, reaction time, concentration performance, accuracy), workload and relevant covariates (salivary cortisol level, heart rate, physical activity, sitting time) were measured pre- and post-intervention under laboratory conditions. MANOVA and RMANOVA results did not show differences in performance parameters and workload, respectively, between sit/stand and traditional workplace users. Differences in text editing accuracy and cortisol levels for sit/stand workstation users indicate potential connectivity to cognitive parameters which should be further examined with large-scale studies. Practitioner summary: Medium-term effects of working at sit/stand workstations on cognitive performance and workload are unexplored. This randomised controlled trial suggests that cognitive performance and workload are unaffected for sit/stand workstation users after 23 weeks of use. However, accuracy appeared to improve and physiological stress appeared to be altered. Abbreviations : BMI: body mass index; IPAQ: International physical activity questionnaire; MET: metabolic equivalent of task; MANOVA: multivariate ANOVA; NASA TLX: NASA task load index; RMANOVA: repeated measures ANOVA.

The extracellular matrix (ECM) plays an essential role in the development, growth and repair of skeletal muscles and serves to transmit contractile force. However, its regulation is poorly understood. This study investigates the age-specificity of the effects of acute resistance exercise on ECM gene expression. To this purpose, five young (YM, 23.8 ± 2.2 yrs.) and 5 elderly (EM, 66.8 ± 4.1 yrs.) men performed one session of unilateral leg press and leg extension exercises. Six hours post-exercise, biopsies were taken from the vastus lateralis muscles of both legs. A PCR array was used to profile the expression of 84 ECM-related genes, of which 6 were validated by qPCR. The PCR array found 9 and 4 ECM-associated genes to be selectively altered (>1.5-fold change) in YM or EM only. Four further genes were upregulated in YM but downregulated in EM. Of the 6 genes validated on individual samples MMP9 expression increased in YM (9.7-fold) and decreased (0.2-fold) in EM. MMP15 was downregulated in EM only (0.6-fold). A significant correlation between leg extension 1 RM and changes in COL7A1 expression (ρ = 0.71) suggests a potential influence of fitness levels. In conclusion, acute resistance exercise affects ECM gene expression at least partly in an age-specific manner. The altered expression of genes encoding matrix metalloproteinases (MMP3, MMP9, MMP15) highlights the role of remodelling processes in the response to an acute bout of resistance exercise. Larger studies are required to verify the age-associated differences in gene expression profiles and establish their functional implications.

Background: Age related loss of skeletal muscle mass is accompanied by changes in muscle quality leading to impairment of functional status., Aim: This study investigated the effect of resistance training and nutritional supply on muscle mass and muscle quality in very old institutionalized adults., Design: Prospective, randomized, multi-arm parallel and controlled intervention study., Setting: This study was conducted in five retirement care facilities., Population: This subgroup of the Vienna Active Ageing Study included 54 women and men (82.4±6.0 years) with impaired health status. Participants were randomly assigned either to elastic band resistance training (N.=16), training with nutritional supplementation (N.=21) or control group (N.=17)., Methods: Health status was assessed at baseline with functional tests, cognitive status, nutritional status, sum of medications as well as sum of diseases. Skeletal muscle mass, determined by dual-energy X-ray absorptiometry, isokinetic knee extension and flexion force and handgrip strength were assessed at baseline and after 6 months. Muscle quality of lower extremities was defined as ratio of the extensor (MQ&#95;LE (Ext.)) or flexor strength (MQ&#95;LE (Flex.)) to lean leg mass. Muscle quality of upper extremity was defined as ratio of handgrip strength to lean arm mass. Follow-up examinations were performed after 12 and 18 months of intervention., Results: Muscle quality, but not muscle mass, showed significant correlations to functional tests at baseline (0.300 - 0.614, P<0.05). Resistance training significantly enhanced muscle quality of lower extremity after 6 months (MQ&#95;LE (Ext.) +19.8%, MQ&#95;LE (Flex.) +30.8%, P<0.05). Nutritional supplementation could not further increase the training effect. Participants with lower muscle quality at baseline benefit most from the training intervention. Skeletal muscle mass was not changed by any intervention., Conclusions: Resistance training with elastic bands improved muscle quality in very old people. Additional nutritional supplementation was not able to further improve the effects obtained by training alone., Clinical Rehabilitation Impact: Elastic band resistance training could be safely used to improve muscle quality even in old people with impaired health status. Weak and chronically ill participants benefit most from this training.

Visceral obesity is frequently associated with the development of type 2 diabetes (T2D), a highly prevalent chronic disease that features insulin resistance and pancreatic β -cell dysfunction as important hallmarks. Recent evidence indicates that the chronic, low-grade inflammation commonly associated with visceral obesity plays a major role connecting the excessive visceral fat deposition with the development of insulin resistance and pancreatic β -cell dysfunction. Herein, we review the mechanisms by which nutrients modulate obesity-associated inflammation.

The purpose of this study was to investigated the effect of age - over or under life-expectancy (LE) - on six months resistance training alone or combined with a nutritional supplement, and cognitive training by analyzing markers for oxidative stress and antioxidant defense in institutionalized elderly, living in Vienna. Three groups (n = 117, age = 83.1 ± 6.1 years) - resistance training (RT), RT combined with protein and vitamin supplementation (RTS) or cognitive training (CT) - performed two guided training sessions per week for six months. Oxidative stress, antioxidant defense and DNA strand breaks were analyzed and transformed into an "antioxidant factor" to compare the total effect of the intervention. Physical fitness was assessed by the 6-min-walking, the chair-rise and the handgrip strength tests. We observed significant negative baseline correlations between 8-oxo-7.8-dihydroguanosine and handgrip strength (r = -0.350, p = 0.001), and between high sensitive troponin-T and the 6-min-walking test (r = -0.210, p = 0.035). RT and RTS groups, showed significant improvements in physical performance. Over LE, subjects of the RT group demonstrated a significant greater response in the "antioxidant factor" compared to RTS and CT (RT vs. RTS p = 0.033, RT vs. CT p = 0.028), whereas no difference was observed between the intervention groups under LE. Six months of elastic band resistance training lead to improvements in antioxidant defense, DNA stability and oxidative damage, summarized in the "antioxidant factor", however mainly in subjects over their statistical LE. Consuming a supplement containing antioxidants might inhibit optimal cellular response to exercise. The study was approved by the ethics committee of the City of Vienna (EK-11-151-0811) and registered at ClinicalTrials.gov, NCT01775111., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Schools are a key setting for large-scale primordial non-communicable disease prevention in young people, but little data on sustainability of impacts on cardiometabolic risk markers is available., Methods: Six and a half year follow-up of a natural experiment. In 2008, six public schools in the municipality of Svendborg (Denmark) augmented their curricular physical education (intervention) and four matched schools served as controls. At long term follow up in 2015 n = 312 participants aged 5-11 years had complete data (33% of children providing necessary baseline data). The intervention, that consisted of a trebling of weekly physical education lessons and courses provided to physical education teachers, was provided at intervention schools up until 6th grade. Participants attended 6th to 10th grade at follow-up. Differences in the homeostasis model assessment of insulin resistance, blood pressure, triglycerides, cholesterol ratios, cardiorespiratory fitness, waist-circumference, and a composite score of these, between participants attending intervention and control schools were analysed by mixed linear regression models. Differences in physical activity at follow-up was analysed cross-sectionally (no baseline available) in n = 495., Results: Compared to controls, children at intervention schools had a non-significant - 0.07 (- 0.32 to 0.18) standard deviations lower composite risk score 6.5 years after project initiation. Likewise, no statistically significant differences between intervention and control schools were found for any of the other outcomes (p-values ≥ 0.41). However, six of seven outcomes were in a direction favouring intervention schools. No statistically significant differences between intervention and control schools were observed for physical activity outcomes (p-values ≥ 0.13)., Conclusions: An augmented physical activity program including 270 min of weekly physical education provided for three to seven years did not materialize in statistically significant differences in established risk markers in children from intervention compared to control schools. As the intervention was discontinued after 6th grade, the post-intervention effect of augmented physical education throughout adolescence is unknown. School-based physical activity programs may benefit from incorporating instruments for behaviour translation to leisure time in their intervention models to increase the probability of achieving public health relevance., Trial Registration: ClinicalTrials.gov Identifier: NCT03510494 .

Background: High physical fitness levels in childhood and adolescence are associated with positive health-related outcomes later in life. Albeit many researchers investigated rural-urban differences in physical fitness, the outcomes of these studies are inconsistent and data on Kosovo are widely missing. Thus, this study aims to examine anthropometric and physical fitness parameters in 14 to 15 year old Kosovan adolescents living in rural and urban areas., Methods: Two schools from Pristina (mostly urban population) and two schools in the surrounding villages of the district of Deçan (mostly rural population) were selected. Anthropometric and physical fitness parameters were determined from a total of 354 adolescents (216 urban: 14.5 ± 0.4 years, 138 rural: age 14.5 ± 0.4 years) who volunteered to participate in this cross-sectional study performed in 2013/14., Results: The prevalence of overweight and obesity was 18.9% in girls and 28.2% in males and excess body fat was detected in 18.2% of the girls and 15.9% of the boys with no differences between rural and urban adolescents. Rural adolescents performed slightly better in relative handgrip strength (+4.7%, p = 0.032) and running speed (10 m: +2.2%, p = 0.012; 20 m: +1.9%, p = 0.035), but no other differences were detected in standing long jump, counter movement jump, cardiorespiratory fitness and sit and reach test. A multinomial logistic regression analysis revealed that being a female was associated with a lower relative risk for overweight (RR = 0.11, 95% CI: 0.03-0.34, p < 0.001) and high body fat content (RR = 0.20, 95% CI: 0.05-0.56, p < 0.001). In addition, higher handgrip strength, longer sprinting time and lower aerobic fitness were associated with a higher relative risk for overweight and excess body fat. In contrast, lower handgrip strength increased the risk for experiencing thinness (RR = 0.92, 95% CI: 0.89-0.96, p < 0.001)., Conclusions: It could be shown that there is a high prevalence of overweight and obesity, especially in 14 to 15 year old boys in Kosovo which does not differ between rural and urban areas. Worse physical performance is associated with a higher risk for overweight and obesity highlighting the importance for interventions in this area and for starting longitudinal observations of a secular trend.

Background: The aim of the present study was to assess the role of eccentric exercise intensity in the development of and recovery from delayed onset muscle soreness (DOMS)., Methods: Using a cross-over study design, 15 healthy, male college students were tested on two occasions. The training stimulus consisted of an exhaustive series of eccentric muscle contractions of the elbow flexors at either 100% (high intensity) or 50% (low intensity) of the individual concentric one-repetition maximum. Blood samples were taken at baseline as well as 24, 48, 72 and 96 hours postexercise, and analyzed for creatine kinase, myoglobin, interleukin-6 and prostaglandin-2. Additionally, upper arm circumference (CIRC) and DOMS-related sensation of pain (PAIN) were measured., Results: Following high intensity training, CIRC was significantly greater (P=0.007). Further, creatine kinase, myoglobin and interleukin-6 tended to be higher, although the main effect of the factor "intensity" just failed to reach significance (creatine kinase: P=0.056, myoglobin: P=0.064, interleukin-6: P=0.091). No differences were found for prostaglandin-2 (P=0.783) and PAIN (P=0.147)., Conclusions: When performed at greater intensity, fatiguing eccentric resistance exercise of the elbow flexors leads to greater muscle swelling and, potentially, increases in serum markers reflecting lesions in the muscle's cellular membrane.

Telomere length (TL) in blood cells is widely used in human studies as a molecular marker of ageing. Circulating cell-free DNA (cfDNA) as well as unconjugated bilirubin (UCB) are dynamic blood constituents whose involvement in age-associated diseases is largely unexplored. To our knowledge, there are no published studies integrating all three parameters, especially in individuals of advanced age. Here we present a secondary analysis from the Vienna Active Aging Study (VAAS), a randomized controlled intervention trial in institutionalized elderly individuals (n = 101). Using an exploratory approach we combine three blood-based molecular markers (TL, UCB and cfDNA) with a range of primary and secondary outcomes from the intervention. We further look at the changes occurring in these parameters after 6-month resistance exercise training with or without supplementation. A correlation between UCB and TL was evident at baseline (p < 0.05), and both were associated with increased chromosomal anomalies such as nucleoplasmatic bridges and nuclear buds (p < 0.05). Of the three main markers explored in this paper, only cfDNA decreased significantly (p < 0.05) after 6-month training and dietary intervention. No clear relationship could be established between cfDNA and either UCB or TL. The trial was registered at ClinicalTrials.gov (NCT01775111).

Background: Ageing, inactivity and obesity are associated with chronic low-grade inflammation contributing to a variety of lifestyle-related diseases. Transforming growth factor-β (TGF-β) is a multimodal protein with various cellular functions ranging from tissue remodelling to the regulation of inflammation and immune functions. While it is generally accepted that aerobic exercise exerts beneficial effects on several aspects of immune functions, even in older adults, the effect of resistance training remains unclear. The aim of this study was to investigate whether progressive resistance training (6 months) with or without nutritional supplementation (protein and vitamins) would influence circulating C-reactive protein and TGF-β levels as well as TGF-β signalling in peripheral mononuclear cells (PBMCs) of institutionalised adults with a median age of 84.5 (65.0-97.4) years., Results: Elastic band resistance training significantly improved performance as shown by the arm-lifting test (p = 0.007), chair stand test (p = 0.001) and 6-min walking test (p = 0.026). These results were paralleled by a reduction in TGF-β receptor I (TGF-βRI) mRNA expression in PBMCs (p = 0.006), while circulating inflammatory markers were unaffected. Protein and vitamin supplementation did not provoke any additional effects. Interestingly, muscular endurance of upper and lower body and aerobic performance at baseline were negatively associated with changes in circulating TGF-β at the early phase of the study. Furthermore, drop-outs of the study were characterised not only by lower physical performance but also higher TGF-β and TGF-βRI mRNA expression, and lower miRNA-21 expression., Conclusions: Progressive resistance training with elastic bands did not influence chronic low-grade inflammation but potentially affected TGF-β signalling in PBMCs through altered TGF-βRI mRNA expression. There appears to be an association between physical performance and TGF-β expression in PBMCs of older adults, in which the exact mechanisms need to be clarified.

Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

Purpose: Regular resistance exercise training and a balanced diet may counteract the age-related muscular decline on a molecular level. The aim of this study was to investigate the influence of elastic band resistance training and nutritional supplementation on circulating muscle growth and degradation factors, physical performance and muscle quality (MQ) of institutionalized elderly., Methods: Within the Vienna Active Ageing Study, 91 women aged 83.6 (65.0-92.2) years were randomly assigned to one of the three intervention groups (RT, resistance training; RTS, resistance training plus nutritional supplementation; CT, cognitive training). Circulating levels of myostatin, activin A, follistatin, IGF-1 and GDF-15, as well as MQ and functional parameters were tested at baseline as well as after 3 and 6 months of intervention., Results: MQ of lower extremities significantly increased in the RT group (+14 %) and RTS group (+12 %) after 6 months. Performance improved in the RT and RTS groups for chair stand test (RT: +18 %; RTS: +15 %). Follistatin increased only in the RT group (+18 %) in the latter phase of the intervention, accompanied by a decrease in the activin A-to-follistatin ratio (-7 %). IGF-1, myostatin and GDF-15 levels were not affected by the intervention., Conclusion: Our data confirm that strength training improves physical performance and MQ even in very old institutionalized women. This amelioration appears to be mediated by blocking muscle degradation pathways via follistatin rather than inducing muscle growth through the IGF-1 pathway. As plasma levels of biomarkers reflect an overall status of various organ systems, future studies of tissue levels are suggested.

Purpose: The aim of the present study was to examine the acute effects of graded physiological strain on soccer kicking performance., Methods: Twenty-eight semi-professional soccer players completed both experimental and control procedure. The experimental protocol incorporated repeated shooting trials combined with a progressive discontinuous maximal shuttle-run intervention. The initial running velocity was 8 km/h and increasing for 1 km/h every 3 min until exhaustion. The control protocol comprised only eight subsequent shooting trials. The soccer-specific kicking accuracy (KA; average distance from the ball-entry point to the goal center), kicking velocity (KV), and kicking quality (KQ; kicking accuracy divided by the time elapsed from hitting the ball to the point of entry) were evaluated via reproducible and valid test over five individually determined exercise intensity zones., Results: Compared with baseline or exercise at intensities below the second lactate threshold (LT2), physiological exertion above the LT2 (blood lactate > 4 mmol/L) resulted in meaningful decrease in KA (11-13%; p < 0.05), KV (3-4%; p < 0.05), and overall KQ (13-15%; p < 0.01). The light and moderate-intensity exercise below the LT2 had no significant effect on soccer kicking performance., Conclusions: The results suggest that high-intensity physiological exertion above the player's LT2 impairs soccer kicking performance. In contrast, light to moderate physiological stress appears to be neither harmful nor beneficial for kicking performance.

The study aimed to evaluate the test-retest reliability of a newly developed 356 Soccer Shooting Test (356-SST), and the discriminative ability of this test with respect to the soccer players' proficiency level and leg dominance. Sixty-six male soccer players, divided into three groups based on their proficiency level (amateur, n = 24; novice semi-professional, n = 18; and experienced semi-professional players, n = 24), performed 10 kicks following a two-step run up. Forty-eight of them repeated the test on a separate day. The following shooting variables were derived: ball velocity (BV; measured via radar gun), shooting accuracy (SA; average distance from the ball-entry point to the goal centre), and shooting quality (SQ; shooting accuracy divided by the time elapsed from hitting the ball to the point of entry). No systematic bias was evident in the selected shooting variables (SA: 1.98±0.65 vs. 2.00±0.63 m; BV: 24.6±2.3 vs. 24.5±1.9 m s-1; SQ: 2.92±1.0 vs. 2.93±1.0 m s-1; all p>0.05). The intra-class correlation coefficients were high (ICC = 0.70-0.88), and the coefficients of variation were low (CV = 5.3-5.4%). Finally, all three 356-SST variables identify, with adequate sensitivity, differences in soccer shooting ability with respect to the players' proficiency and leg dominance. The results suggest that the 356-SST is a reliable and sensitive test of specific shooting ability in men's soccer. Future studies should test the validity of these findings in a fatigued state, as well as in other populations.

Objectives: To evaluate the effects of elastic band resistance training in combination with nutrient supplementation on muscular strength and the ability to perform mobility-related activities of daily living in older adults living in retirement care facilities., Design: Randomized controlled trial, with a 6-month intervention period., Setting: A retirement care facility, Vienna, Austria., Participants: One hundred and seventeen older adults (14 males (12%) and 103 females (88%)), aged 65 to 97 years (mean age: 82.8 ± 6.0), having a mini-mental state examination score ≥ 23 and no chronic diseases posing a medical contraindication to training therapy., Intervention: Participants were randomly assigned, but stratified by sex, to one of three intervention groups: supervised resistance exercise training (RT), RT in combination with nutrient supplementation (RTS), or cognitive training group (CT). All interventions were performed two times a week for 6 months. RT was designed to train all major muscle groups using elastic bands. The nutrient supplement (rich in proteins, vitamin D, B2, B12) was distributed every morning as well as after each RT session., Measurements: A battery of motor ability tests and functional test were performed prior to as well as following 3 months and finally after 6 months of intervention. These tests included isokinetic torque measurements of the knee extensors and flexors in concentric mode at 60 and 120°/s, isometric handgrip strength, senior arm-lifting test, chair stand test, maximum walking speed and a 6-minute walking test (6 MWT)., Results: A repeated-measures ANOVA analysis revealed significant improvements in physical function of lower (p=0.002) and upper extremities (p=0.006) for RT and/or RTS in comparison to CT. For isokinetic measurements, 6 MWT, and gait speed time effects (p<0.05) were detected without any group × time interaction effects. Dropouts showed lower performance in chair stand test (p=0.012), 6 MWT (p=0.003), and gait speed (p=0.013) at baseline than that of the finishers of the study., Conclusion: Six months of a low intensity resistance exercise using elastic bands and own body weight is safe and beneficial in improving functional performance of institutionalised older people. Multinutrient supplementation did not offer additional benefits to the effects of RT in improving muscular performance., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Gait variability is an important indicator of gait performance. However, the reliability of the parameters used for its quantification, obtained from trunk linear accelerations, has still not been thoroughly investigated. The aim of this study is to assess the reliability of gait variability assessment in healthy older individuals based on lower trunk accelerations during a six-minute walk test and to examine the reliability of the data acquired in shorter periods. Twenty-nine subjects (84±5 years) performed the test while wearing one inertial sensor on the lower trunk. Gait variability parameters (standard deviation and coefficient of variation of the stride duration, and correlation coefficients of accelerations between neighbouring strides) were calculated from the accelerations over 35 rectilinear strides observed during six series of one-minute intervals extracted from the original signal. The reliability of these parameters was assessed using intraclass correlation coefficients (ICC). Results showed no significant changes across the six series for any of the parameters, with very high ICC values (0.93-0.95), indicating a strong reliability of the observed quantities. Therefore, gait variability analysis based on lower trunk acceleration data is a reliable and informative quantity in gait performance assessment in older individuals, and 1min interval is sufficient to ensure reliable results., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Increased DNA and chromosomal damage are linked to aging and age-related diseases like cardiovascular diseases, diabetes or cancer. Physical activity and an optimal status of micro- and macronutrients are known to reduce the incidence of MN, a marker for chromosomal instability and mutagenicity. Once older people reach a certain age they change from a home-living situation to an institutionalized situation, which is often accompanied by malnutrition, depression and inactivity. We conducted the current study to investigate the effect of a six month progressive resistance training (RT), with or without protein and vitamin supplementation (RTS) or cognitive training (CT) only, on chromosomal damage measured by the cytokinesis block micronucleus cytome assay in 97 Austrian institutionalized women and men (65-98years). All three intervention groups demonstrated a tendency of a reduced frequency of cells with MN (-15%) as well as for the total number of MN (-20%), however no significant time-effect was observed. Besides a significant increase in plasma B12 and red blood cell folate status, the six month change of B12 was negatively correlated with the six month change of the MN frequency in the RTS group (r=-0.584, p=0.009). Our results suggest that in this age group either physical or cognitive training may result in similar biochemical changes and therefore enhance resistance against genomic instability. Supplementation with the vitamins B12 and folic acid could contribute to reduced chromosomal damage in institutionalized elderly., (Copyright © 2015 Elsevier Inc. All rights reserved.)

There is a high need for blood-based biomarkers detecting age-related changes in muscular performance at an early stage. Therefore, we investigated whether serum levels of growth and differentiation factor-15 (GDF-15), activin A, myostatin, follistatin, and insulin-like growth factor-1 (IGF-1) would reflect age- and physical performance-related differences between young (22-28 years) and elderly (65-92 years) females. Isokinetic peak torque of knee extension (PTE) was measured in young females to obtain reference values for the discrimination of different stages of age-associated muscle weakness. Additionally, elderly women were screened for sarcopenia using the algorithm of the European Working Group on Sarcopenia in Older People (low muscle mass in addition to low PTE and/or low walking speed). IGF-1 levels were higher and GDF-15 levels were lower in young females in comparison to the elderly (p < 0.01), whereas members of the activin A/myostatin/follistatin axis showed similar levels across age groups. In older women, IGF-1 correlated negatively with age (ρ = -0.359, p < 0.01) and positively with muscle mass (ρ = 0.365, p < 0.01). In contrast, GDF-15 correlated positively with age (ρ = 0.388, p < 0.001) and negatively with muscle mass (ρ = -0.320, p < 0.01). However, none of the serum markers differed between women classified as non-, mildly and severely dynapenic/sarcopenic. Multiple linear regression analyses revealed that a combination of all blood-based biomarkers obtained in addition to age and fat mass moderately predicted muscle mass (+2.9%). Neither a single nor a combined set of tested biomarkers reflected the presence of dynapenia or sarcopenia in elderly women. However, due to the associations of IGF-1 and GDF-15 with correlates of muscle mass and function, these parameters remain promising candidates in a potential set of blood-based biomarkers to diagnose sarcopenia and/or dynapenia., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aging and its aligned loss of muscle mass are associated with higher levels of DNA damage and deteriorated antioxidant defence. To improve the body's overall resistance against DNA damage, maintaining a healthy and active lifestyle is desirable, especially in the elderly. As people age, many have to change their residence from home living to an institution, which is often accompanied by malnutrition, depression and inactivity. The current study aimed at investigating the effect of a 6-month progressive resistance training (RT), with or without protein and vitamin supplementation (RTS), or cognitive training (CT), on DNA strand breaks in 105 Austrian institutionalised women and men (65-98 years). DNA damage was detected by performing the single cell gel electrophoresis (comet) assay. Physical fitness was assessed using the chair rise, the 6-min-walking and the handgrip strength test. In addition, antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were analysed. Basal DNA damage (lysis) increased significantly after 3 months of intervention in the RT group (T1 - T2 + 20%, P = 0.001) and the RTS group (T1 - T2 + 17%, P = 0.002) and showed a similar tendency in the CT group (T1 - T2 + 21%, P = 0.059). %DNA in tail decreased in cells exposed to H2O2 significantly in the RT (T1 - T2 - 24%, P = 0.030; T1 - T3 - 18%, P = 0.019) and CT (T1 - T2 - 21%, P = 0.004; T1 - T3 - 13%, P = 0.038) groups. Only RT and RTS groups showed significant differences overtime in enzyme activity (RT + 22% CAT-activity T1 - T3, P = 0.013; RTS + 6% SOD-activity T2 - T3, P = 0.005). Contrary to the time effects, no difference between groups was detected for any parameter at any time point. Our results suggest that both CT and RT improve resistance against H2O2 induced DNA damage and that a nutritional supplement has no further protective effect in institutionalised elderly., (© The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The TGF-β superfamily has been shown to play an important role in a wide range of physiological as well as pathological processes including ageing, immune modulation, atherosclerosis and cancer development. The aim of the current study was to investigate (i) whether TGF-β signalling in peripheral blood mononuclear cells (PBMCs) would differ between young and old females and (ii) whether physical performance parameters of elderly women would be related to the expression of TGF-β or its receptors. Sixteen healthy young (22-28 years; YF) and 90 healthy older (65-92 years; OF) females participated in the study. In addition to several components of health-related physical fitness, circulating CRP and TGF-β levels were determined together with the mRNA expression of TGF-β, TGF-βRI, TGF-βRII, and miRNA-21 (known to interfere with TGF-β signalling) in PBMCs. Physical fitness as determined by 6-minutes walking test (YF:median 932 (range 573-1254) m; OF:360 (114-558) m), handgrip strength (YF: 32 (24-39) kg; OF:18(10-30) kg), relative isokinetic peak torque of knee extensors (YF:1.9 (1.2- 2.3) Nm/kg; OF:1.0 (0.2-1.9) Nm/kg and flexors (YF: 1.1 (0.7- 1.5) Nm/kg; OF: 0.5 (0.2-1.0) Nm/kg was substantially lower in older women (p<0.001 for all comparisons). These changes were paralleled by an increase in hs-CRP (YF: 0.9 (0.1-4.3)mg/L; OF: 2.3 (0.3-56.7)mg/L,p<0.001). Serum levels of TGF-β and TGF-β mRNA levels from PBMCs did not differ between young and old women whereas, both TGF- βRI/GAPDH (YF: 4.07 (1.38-14.60); OF: 2.08 (0.14-28.81); p=0.020) and TGF-βRII/GAPDH levels (YF: 3.16 (1.14- 10.25); OF: 1.71 (0.51-14.86); p=0.020) were lower with respect to old age. In elderly women, only TGF-βRΙ expression correlated negatively with miRNA-21 expression in PBMCs (ρ=-0.315; p=0.004). Interestingly, hs-CRP and miRNA correlated positively with handgrip strength (ρ=0.237 and ρ=243, p<0.05), while none of the TGF-β-related parameters were related to physical performance. The results suggest that age affects TGF-β signalling in leukocytes by altering the expression levels of its receptors. These changes seem to occur independently of physical fitness of old women., (Copyright © 2015 International Society of Exercise and Immunology. All rights reserved.)

Ageing goes hand in hand with altered DNA repair and defence mechanisms against DNA damage. To improve the body's overall resistance against chromosomal damage, maintaining a healthy and active lifestyle is of great concern, especially in the elderly. As more and more people are getting older, they change from home living to an institutionalised situation, which is often accompanied by malnutrition, depression and inactivity. So far, there is a lack of data on chromosomal damage in relation to age and fitness status. The aim of this study was to examine the effect of age and aerobic fitness on endpoints of DNA damage in 105 institutionalised women and men (65-98 years) living in Vienna. Chromosomal damage was measured by conducting the cytokinesis block micronucleus cytome assay. Aerobic fitness of the participants was assessed using the 6-min walking test. To investigate the effect of age on micronuclei (MN) frequency and evaluate the particular age group, our data were merged with data from a recent study by Wallner et al. (Effects of unconjugated bilirubin on chromosomal damage in individuals with Gilbert's syndrome measured with the micronucleus cytome assay. Mutagenesis 2012; 27: 731-735). Age and MN frequency correlated significantly for squared regression (r = 0.577; P = 0.000) and showed a levelling-off at ~60 years of age. Furthermore, we observed a significant negative linear correlation (r = -0.222; P = 0.03) between MN frequency and 6-min walking performance. There was a plateau-like effect of the MN frequency above the age of 60-70 years, indicating a higher resistance against chromosomal damage of the 'survivors' of the regular lifespan. This study suggests that aerobic fitness 'protects' against chromosomal damage at high age., (© The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Reprogramming of gene expression is fundamental for skeletal muscle adaptations in response to endurance exercise. This study investigated the time course-dependent changes in the muscular transcriptome after an endurance exercise trial consisting of 1 h of intense cycling immediately followed by 1 h of intense running. Skeletal muscle samples were taken at baseline, 3 h, 48 h, and 96 h postexercise from eight healthy, endurance-trained men. RNA was extracted from muscle. Differential gene expression was evaluated using Illumina microarrays and validated with qPCR. Gene set enrichment analysis identified enriched molecular signatures chosen from the Molecular Signatures Database. Three hours postexercise, 102 gene sets were upregulated [family wise error rate (FWER), P < 0.05], including groups of genes related with leukocyte migration, immune and chaperone activation, and cyclic AMP responsive element binding protein (CREB) 1 signaling. Forty-eight hours postexercise, among 19 enriched gene sets (FWER, P < 0.05), two gene sets related to actin cytoskeleton remodeling were upregulated. Ninety-six hours postexercise, 83 gene sets were enriched (FWER, P < 0.05), 80 of which were upregulated, including gene groups related to chemokine signaling, cell stress management, and extracellular matrix remodeling. These data provide comprehensive insights into the molecular pathways involved in acute stress, recovery, and adaptive muscular responses to endurance exercise. The novel 96 h postexercise transcriptome indicates substantial transcriptional activity potentially associated with the prolonged presence of leukocytes in the muscles. This suggests that muscular recovery, from a transcriptional perspective, is incomplete 96 h after endurance exercise involving muscle damage.

High Capacity Runner (HCR) rats have been developed by divergent artificial selection for treadmill endurance running capacity to explore an aerobic biology-disease connection. The beneficial effects of resveratrol supplementation have been demonstrated in endurance running and the antioxidant capacity of resveratrol is also demonstrated. In this study we examine whether 12 weeks of treadmill exercise training and/or resveratrol can enhance performance in HCR. Indeed, resveratrol increased aerobic performance and strength of upper limbs of these rats. Moreover, we have found that resveratrol activated the AMP-activated protein kinase, SIRT1, and mitochondrial transcription factor A (p<0.05). The changes in mitochondrial fission/fusion and Lon protease/HSP78 levels suggest that exercise training does not significantly induce damage of proteins. Moreover, neither exercise training nor resveratrol supplementation altered the content of protein carbonyls. Changes in the levels of forkhead transcription factor 1 and SIRT4 could suggest increased fat utilization and improved insulin sensitivity. These data indicate, that resveratrol supplementation enhances aerobic performance due to the activation of the AMPK-SIRT1-PGC-1α pathway., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.

This article discusses the inevitable use of growth factors for enhancing muscle strength and athletic performance. Much effort has been expended on developing a treatment of muscle wasting associated with a range of diseases and aging. Frailty in the aging population is a major socioeconomic and medical problem. Emerging molecular techniques have made it possible to gain a better understanding of the growth factor genes and how they are activated by physical activity. The ways that misuse of growth factors may be detected and verified in athletes and future challenges for detecting manipulation of signaling pathways are discussed., (Copyright 2010. Published by Elsevier Inc.)

With the discovery of microRNAs (miRNAs), an exceptional means of regulating gene expression was introduced a few years ago. MiRNAs function to inactivate specific messenger RNA transcripts leading to depletion of the corresponding protein, whereby computational studies have shown that about one third of all animal genes might be miRNA targets. Recent publications highlight the involvement of miRNAs in regulating the immune response. The aim of this review is to provide an overview of miRNA biogenesis and function, to illustrate their impact on both the innate as well as the adaptive immune system, to show the regulation of skeletal muscle plasticity and inflammation, and finally to present their possible role within the field of exercise immunology.

Growth factors (GFs) act as signalling agents for cells and become a more and more popular mean to influence the human body and its tissues. This review gives an overview of the current possibilities to use such agents in the field of sports related injuries and thus providing the athlete with a whole new potential to minimize recovery time. GFs and its application have been studied intensively for a long time starting with animal studies. For some of this GFs this research has been brought onto the next level to clinical phase trials. Agents such as insulin like growth factor 1 (IGF-1), mechano growth factor (MGF), basic fibroblast growth factor (B-FGF), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor b (TGF-b), bone morphogenetic protein (BMP) and leukemia inhibitory factor (LIF) are being discussed in this review. These GFs not only have the potential to be used to cure injuries but also are being in the centre of interest for doping abusers and are a powerful yet not fully understood technique to gain performance.

Prolonged or repeated stimulation of Toll-like receptor (TLR) 4 leads to hyporesponsiveness of monocyte-derived macrophages, which seems to be a hallmark of immunosuppression related to sepsis and cancer. Two negative regulators of TLR-4 signaling are IL-1 receptor-associated kinase M and B-cell leukemia 3. Here, we demonstrate that the expression of both proteins is inhibited when the TLR-7/TLR-8 agonist CL097 is added to monocyte cultures despite costimulation with the TLR-4 agonist LPS or hyaluronic acid. Reduction of IL-1 receptor-associated kinase M and B-cell leukemia 3 was paralleled by a significant increased cytokine induction of TNF-alpha, IL-10, and IL-12 observed after intracellular and extracellular TLR stimulation. In ex vivo stimulated whole blood of patients who have prolonged sepsis or metastatic cancer, TLR-7/TLR-8 agonists retained their ability of increased stimulation of TNF-alpha. These data might add to the understanding of sepsis and cancer-associated immune suppression in men.

Objective: To investigate the effect of neuromuscular electrical stimulation (NMES) on skeletal muscle metabolism after major abdominal surgery., Summary Background Data: Protein catabolism associated with surgical interventions leads to reduced muscle strength, increased clinical complications and prolonged convalescence. Immobilization is suggested as a major stimulus for muscle wasting. This study investigates the potency of NMES on skeletal muscle growth factors and degradation processes in surgical patients., Methods: This observer blind study included 26 patients after major abdominal surgery mainly due to cancer aged 60 +/- 10 years. Starting on the first postoperative day, 1 randomly assigned thigh of each patient was treated on 4 consecutive days with NMES, whereas the other leg was used as sham-stimulated control. Thereafter, muscle biopsies from both legs were performed. Differences in mRNA level, protein expression, and enzyme activity between legs were analyzed by cross-over analysis of variance (Clinical Trial Registration Number: NCT00635440)., Results: NMES significantly increased total RNA content and total sarcoplasmatic protein content. NMES significantly reduced ubiquitin-conjugated sarcoplasmatic proteins and proteasome activity. The mechano growth factor mRNA level correlated positively with the applied current and negatively with the body mass index of the patients. The increase in insulin like growth factor-1Ea mRNA after NMES correlated negatively with the age of the patients., Conclusions: This study shows that NMES significantly increases total RNA content and reduces protein degradation in postoperative patients. Moreover, the induction of growth factors by NMES reveals dependency on body mass index, age, and applied current. We conclude that NMES is a useful clinical tool to reduce protein catabolism in postoperative patients.

Recently we showed that the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) sensitizes arsenic trioxide (As2O3)-resistant tumor cells to a clinically achievable concentration (1 microM) of As2O3 via a reactive oxygen species (ROS)-dependent mechanism. The aim of the present study was to evaluate, whether this combined effect of As2O3 and DHA is also applicable to other PUFAs [i.e., eicospentaenoic acid (EPA), arachidonic acid (AA), and gamma-linolenic acid (GLA)]. Fourteen tumor cell lines were incubated with As2O3 (1 microM), PUFA (25-100 microM), or the combination thereof (+/- vitamin E). Cell viability (colorimetric), apoptosis (bivariate annexin V/propidium iodide staining, detection of hypodiploid DNA), and thiobarbituric acid reactive substances (TBARS) were evaluated. Twelve of 14 As2O3-resistant cell lines tested were resistant to PUFA monotherapy. However, combined treatment with As2O3 and either PUFA significantly reduced cell viability in a dose-dependent manner with AA being the most potent As2O3 enhancer. The combined cytotoxic effect of As2O3/AA treatment was due to induction of apoptosis, preceded by increased intracellular TBARS and was abolished by the antioxidant vitamin E. Importantly, the combined effect of As2O3 and AA was selectively toxic for malignant cells because no cytotoxic effect was observed in normal skin fibroblasts and human microvascular endothelial cells. In conclusion, our study shows that also other PUFAs than DHA-and in particular the omega-6-PUFA AA--can be used as effective modulators of tumor cell chemosensitivity to clinically achievable concentrations of As2O3. Enhanced lipid peroxidation most likely constitutes the key mechanism for the combined effect.

Electromagnetic interventions in general and those considering the musculoskeletal system in particular hold many obscurities. Several studies revealing positive effects of electromagnetic fields oppose those showing no beneficial effects. After a historical review and a discussion of basic details on electromagnetic signals, this article provides information on the effects of electromagnetic fields on a cellular level and gives an account of preclinical and clinical studies focused on electromagnetic interventions by means of weak pulsed electromagnetic fields on musculoskeletal disorders.

Background & Aims: Reports regarding the pro- or anti-inflammatory effects of lipid emulsion used in parenteral nutrition are conflicting. Aim was to assess the effect of different intravenous lipid emulsions on immunological function in humans., Methods: We performed a computerized bibliographic search, searched reference lists in trial reports, hand-searched journals and contacted experts in the field. Randomized clinical trials evaluating the immunological effects of different parenteral lipid emulsions were included. Three authors independently performed data extraction, statistical processes were performed by two experts. Immunological parameters were classified by two immunologists as marker of improved or worsened immune function. A meta-analysis with standardized effect size estimation was performed for the comparison between long-chain triglycerides vs. glucose or other fat emulsions., Results: Of 682 assessed studies, 120 compared the immunological effects of intravenously applied lipid emulsions. Of 30 randomized trials, 14 were included in the meta-analysis. None of the lipid regimens showed any clear effect on the evolution of the immunological status or mortality in humans. Length of hospital stay and stay in the intensive care unit could not be evaluated., Conclusion: We found no evidence that lipid emulsions and in particular those containing long-chain triglycerides have an unfavorable effect on immune function.

The chemotherapeutic agent irinotecan (IT) is highly effective against several types of cancer, although its use is limited due to severe intestinal toxicity. The aim of this study was to evaluate inflammatory and oxidative stress-related processes contributing to small intestinal mucosa damage and to determine the extent to which green tea polyphenols could ameliorate the detrimental effects induced by IT. In Expt. 1, mice were challenged intraperitoneally with IT or saline on 2 consecutive days. For time kinetic measurements, the IT-treated mice were killed at 3, 24, 48, 72, and 96 h after the 2nd dose of IT. Three hours after IT administration, the ileum glutathione concentration dropped significantly. Lipid peroxidation and inflammation, as measured by macrophage inflammatory protein-2 content, myeloperoxidase activity, and nuclear factor-kappaB translocation, were highest between 24 and 48 h after IT treatment. In Expt. 2, green tea polyphenols (1 g/L) were supplied via drinking water for 7 d before and 3 d after treatment with IT. Green tea polyphenols significantly affected the glutathione:glutathione disulfide ratio but not lipid peroxidation, macrophage inflammatory protein-2 levels, myeloperoxidase activity, or nuclear factor-kappaB activation. Our study reveals that IT administration is associated with oxidative stress and inflammation, both occurring simultaneously to IT-induced mucosal damage. The antioxidative defense is affected soon after IT administration. Green tea polyphenols supplied orally protected against oxidation in our experimental model and could be one approach to reducing the risk of IT-induced side effects in the clinical setting.

Skeletal muscle atrophy is associated with situations of acute and chronical illness, such as sepsis, surgery, trauma and immobility. Additionally, it is a common problem during the physiological process of aging. The myofibrillar proteins myosin and actin, which are essential for muscle contraction, are the major targets during the process of protein degradation. This leads to a general loss of muscle mass, muscle strength and to increased muscle fatigue. In critically ill or immobile patients skeletal muscle atrophy is accompanied by enhanced inflammation, reduced wound healing, weaning complications and difficulties in mobilisation. During aging it results in falls, fractures, physical injuries and loss of mobility. Relating to the primary stimulators - hormones, muscle lengthening, stress, inflammation, neuronal activity - research is now focusing on the investigation of the signal transduction pathways, which influence protein synthesis and protein degradation during skeletal muscle atrophy.

Background: An overwhelming production of reactive oxygen species concomitant with a decrease in antioxidative capacity plays an important role in modulation of the immune system in critically ill patients. The purpose of this study was to assess the influence of a combined oral supply of the antioxidants R-alpha-lipoic acid (LA) and glutamine (GLN) on the immunity of endotoxemic mice, with a special focus on tissue glutathione levels., Methods: Female Balb/c mice were fed diets enriched with GLN (3 g/100 kcal), LA (0.74 mg/100 kcal), a combination of GLN and LA, or an isocaloric and isonitrogenous control diet for 10 days. On day 7, the mice were challenged intraperitoneally with 25 microg lipopolysaccharide. Seventy-two hours later, the number and phenotype of lymphocytes in Peyer's patches (PP) and spleen of the endotoxemic mice were measured. In addition, glutathione levels were determined in the small intestine, spleen and liver., Results: In PP only the combined supply of GLN and LA significantly increased the total cell yield (+19%), which was predominantly due to an increased number of B cells. In the spleen, both LA (+17%) and the combination of GLN and LA (+22%) were able to enhance total cell yield. The glutathione content of the small intestine was increased by feeding LA alone, whereas in the spleen GLN plus LA was most effective., Conclusion: Supplying combined GLN and LA to endotoxemic mice is effective in selectively increasing the number of systemic and intestinal B lymphocytes. Furthermore, LA augmented the level of the main intracellular antioxidant glutathione in the small intestine. On the basis of these data we recommend investigation of the effects of LA and GLN supplementation in patients with sepsis.

Multiple trauma patients have an impaired immune system and thus frequently develop life-threatening septic complications. Because there is an ongoing debate on which are the most predictive immunologic parameters of clinical outcome, we prospectively studied 19 multiple trauma patients with sepsis (mean age, 38.7 +/- 15.8 years; mean Injury Severity Score, 40.6 +/- 11.6) over a period of 14 days. The following parameters were measured daily after admission to the intensive care unit: ex vivo lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production, monocyte human leukocyte antigen (HLA)-DR expression, constitutive interleukin (IL) 6 secretion, white blood cell count, and C-reactive protein. In addition, procalcitonin, neopterin, LPS-binding protein, and constitutive TNF-alpha secretion were measured every third day. Immediately after trauma, all patients had significantly lower levels of HLA-DR and ex vivo LPS-stimulated TNF-alpha secretion than healthy controls (n = 7; P < 0.001). On the day after clinical diagnosis of sepsis, before any other parameter differed between survivors (n = 13) and nonsurvivors (n = 6), ex vivo LPS-induced TNF-alpha secretion was significantly lower (P < 0.05) in nonsurvivors than in survivors. We conclude that ex vivo LPS-induced TNF-alpha production is an earlier predictor of clinical outcome in multiple trauma patients with sepsis than monocyte HLA-DR expression, constitutive IL-6 secretion, or any other parameter assessed.

Toll-like receptors (TLR) represent an ancient front-line defence system that enables the host organism to sense the presence of microbial components within minutes. As inducers of inflammation, TLR act as important triggers of distinct entities such as sepsis or autoimmune disease exacerbation. We report here that vitamin D3 [1alpha,25-dihydroxycholecalciferol, 1,25(OH)(2)D3] suppresses the expression of TLR2 and TLR4 protein and mRNA in human monocytes in a time- and dose-dependent fashion. Despite 1,25(OH)(2)D3-induced up-regulation of CD14, challenge of human monocytes with either LPS or lipoteichoic acid resulted in impaired TNF-alpha and procoagulatory tissue factor (CD142) production, emphasizing the critical role of TLR in the induction of inflammation. Moreover, reduced TLR levels in 1,25(OH)(2)D3-treated phagocytes were accompanied by impaired NF-kappaB/RelA translocation to the nucleus and by reduced p38 and p42/44 (extracellular signal-regulated kinase 1/2) phosphorylation upon TLR-ligand engagement. Both TLR down-regulation and CD14 up-regulation were substantially inhibited by the vitamin D receptor (VDR) antagonist ZK 159222, indicating that the immunomodulatory effect of 1,25(OH)(2)D3 on innate immunity receptors requires VDR transcription factor activation. Our data provide strong evidence that 1,25(OH)(2)D3 primes monocytes to respond less effectively to bacterial cell wall components in a VDR-dependent mechanism, most likely due to decreased levels of TLR2 and TLR4.