This study examines the association between aerobic capacity and biomarkers of skeletal- and cardiac muscle damage among amateur triathletes after a full distance Ironman. Men and women (N = 55) were recruited from local sport clubs. One month before an Ironman triathlon, they conducted a 20 m shuttle run test to determine aerobic capacity. Blood samples were taken immediately after finishing the triathlon, and analyzed for cardiac Troponin T (cTnT), Myosin heavy chain-a (MHC-a), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), Creatin Kinas (CK), and Myoglobin. Regression models examining the association between the biomarkers and aerobic capacity expressed in both relative terms (mLO2*kg-1*min-1) and absolute terms (LO2*min-1) controlled for weight were fitted. A total of 39 subjects (26% females) had complete data and were included in the analysis. No association between aerobic capacity and cardiac muscle damage was observed. For myoglobin, adding aerobic capacity (mLO2*kg-1*min-1) increased the adjusted r2 from 0.026 to 0.210 (F: 8.927, p = 0.005) and for CK the adjusted r2 increased from -0.015 to 0.267 (F: 13.778, p = 0.001). In the models where aerobic capacity was entered in absolute terms the adjusted r2 increased from 0.07 to 0.227 (F: 10.386, p = 0.003) for myoglobin and for CK from -0.029 to 0.281 (F: 15.215, p < 0.001). A negative association between aerobic capacity and skeletal muscle damage was seen but despite the well-known cardio-protective health effect of high aerobic fitness, no such association could be observed in this study.
The impact of high-intensity interval training (HIIT) on the central nervous system (CNS) in autoimmune neuroinflammation is not known. The aim of this study was to determine the direct effects of HIIT on the CNS and development of experimental autoimmune encephalomyelitis (EAE). Healthy mice were subjected to HIIT by treadmill running and the proteolipid protein (PLP) transfer EAE model was utilized. To examine neuroprotection, PLP-reactive lymph-node cells (LNCs) were transferred to HIIT and sedentary (SED) mice. To examine immunomodulation, PLP-reactive LNCs from HIIT and SED donor mice were transferred to naïve recipients and analyzed in vitro. HIIT in recipient mice did not affect the development of EAE following exposure to PLP-reactive LNCs. HIIT mice exhibited enhanced migration of systemic autoimmune cells into the CNS and increased demyelination. In contrast, EAE severity in recipient mice injected with PLP-reactive LNCs from HIIT donor mice was significantly diminished. The latter positive effect was associated with decreased migration of autoimmune cells into the CNS and inhibition of very late antigen (VLA)-4 expression in LNCs. Thus, the beneficial effect of HIIT on EAE development is attributed solely to systemic immunomodulatory effects, likely because of systemic inhibition of autoreactive cell migration and reduced VLA-4 integrin expression.
Middle-aged adults engaging in unhealthy lifestyle behaviors are at higher risk of chronic diseases. However, little is known about the co-occurrence of these behaviors and their determinants. This cohort study examined the co-occurrence of unhealthy lifestyle behaviors (alcohol consumption, diet, physical inactivity, and smoking) in 30,154 middle-aged adults and their associations with sociodemographic factors, social support, and disease history. Alcohol use was measured by the AUDIT, diet by the MiniMeal-Q, and physical inactivity and smoking by single questions. Participants had a mean age of 58 years, with 51% being female. Of them, 14% had no unhealthy behaviors, 38% had one, 36% had two, 10% had three, and 2% had all four. The most common co-occurrence was between physical inactivity and poor diet (38%). Higher education decreased the likelihood of having three or four unhealthy behaviors, while financial difficulties, having no one around who appreciated one's efforts, and suffering of a lung disease increased it. In conclusion, middle-aged adults exhibit varying levels of unhealthy lifestyle behaviors. Higher education is linked to reduced engagement in multiple unhealthy behaviors, whereas financial strain, lower quality of social support, and lung disease increase the risk.
Chronotype reflects individual preferences for timing activities throughout the day, determined by the circadian system, environment and behavior. The relationship between chronotype, physical activity, and cardiovascular health has not been established. We studied the association between chronotype, physical activity patterns, and an estimated 10-year risk of first-onset cardiovascular disease (CVD) in the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort. A cross-sectional analysis was performed in a middle-aged population (n = 812, 48% male). Self-assessed chronotype was classified as extreme morning, moderate morning, intermediate, moderate evening, or extreme evening. Time spent sedentary (SED) and in moderate to vigorous physical activity (MVPA) were derived from hip accelerometer. The newly introduced Systematic COronary Risk Evaluation 2 (SCORE2) model was used to estimate CVD risk based on gender, age, smoking status, systolic blood pressure, and non-HDL cholesterol. Extreme evening chronotypes exhibited the most sedentary lifestyle and least MVPA (55.3 ± 10.2 and 5.3 ± 2.9% of wear-time, respectively), with a dose-dependent relationship between chronotype and SED/MVPA (p < 0.001 and p = 0.001, respectively). In a multivariate generalized linear regression model, extreme evening chronotype was associated with increased SCORE2 risk compared to extreme morning type independent of confounders (β = 0.45, SE = 0.21, p = 0.031). Mediation analysis indicated SED was a significant mediator of the relationship between chronotype and SCORE2. Evening chronotype is associated with unhealthier physical activity patterns and poorer cardiovascular health compared to morning chronotype. Chronotype should be considered in lifestyle counseling and primary prevention programs as a potential modifiable risk factor.
Skeletal muscle architecture significantly influences the performance capacity of a muscle. A DTI-based method has been recently considered as a new reference standard to validate measurement of muscle structure in vivo. This study sought to quantify muscle architecture parameters such as fascicle length (FL), pennation angle (PA) and muscle thickness (tm) in post-stroke patients using diffusion tensor imaging (DTI) and to quantitatively compare the differences with 2D ultrasonography (US) and DTI. Muscle fascicles were reconstructed to examine the anatomy of the medial gastrocnemius, posterior soleus and tibialis anterior in seven stroke survivors using US- and DTI-based techniques, respectively. By aligning the US and DTI coordinate system, DTI reconstructed muscle fascicles at the same scanning plane of the US data can be identified. The architecture parameters estimated based on two imaging modalities were further compared. Significant differences were observed for PA and tm between two methods. Although mean FL was not significantly different, there were considerable intra-individual differences in FL and PA. On the individual level, parameters measured by US agreed poorly with those from DTI in both deep and superficial muscles. The significant differences in muscle parameters we observed suggested that the DTI-based method seems to be a better method to quantify muscle architecture parameters which can provide important information for treatment planning and to personalize a computational muscle model.
Emerging concepts for on-chip biotechnologies aim to replace microfluidic flow by active, molecular-motor driven transport of cytoskeletal filaments, including applications in bio-simulation, biocomputation, diagnostics, and drug screening. Many of these applications require reliable detection, with minimal data acquisition, of filaments at many, local checkpoints in a device consisting of a potentially complex network of channels that guide filament motion. Here we develop such a detection system using actomyosin motility. Detection points consist of pairs of gold lines running perpendicular to nanochannels that guide motion of fluorescent actin filaments. Fluorescence interference contrast (FLIC) is used to locally enhance the signal at the gold lines. A cross-correlation method is used to suppress errors, allowing reliable detection of single or multiple filaments. Optimal device design parameters are discussed. The results open for automatic read-out of filament count and velocity in high-throughput motility assays, helping establish the viability of active, motor-driven on-chip applications.
Cognitive aging creates major individual and societal burden, motivating search for treatment and preventive care strategies. Behavioural interventions can improve cognitive performance in older age, but effects are small. Basic research has implicated dopaminergic signalling in plasticity. We investigated whether supplementation with the dopamine-precursor L-dopa improves effects of cognitive training on performance. Sixty-three participants for this randomised, parallel-group, double-blind, placebo-controlled trial were recruited via newspaper advertisements. Inclusion criteria were: age of 65-75 years, Mini-Mental State Examination score >25, absence of serious medical conditions. Eligible subjects were randomly allocated to either receive 100/25 mg L-dopa/benserazide (n = 32) or placebo (n = 31) prior to each of twenty cognitive training sessions administered during a four-week period. Participants and staff were blinded to group assignment. Primary outcomes were latent variables of spatial and verbal fluid intelligence. Compared to the placebo group, subjects receiving L-dopa improved less in spatial intelligence (-0.267 SDs; 95%CI [-0.498, -0.036]; p = 0.024). Change in verbal intelligence did not significantly differ between the groups (-0.081 SDs, 95%CI [-0.242, 0.080]; p = 0.323). Subjects receiving L-dopa also progressed slower through the training and the groups displayed differential volumetric changes in the midbrain. No statistically significant differences were found for the secondary cognitive outcomes. Adverse events occurred for 10 (31%) and 7 (23%) participants in the active and control groups, correspondingly. The results speak against early pharmacological interventions in older healthy adults to improve broader cognitive functions by targeting the dopaminergic system and provide no support for learning-enhancing properties of L-dopa supplements in the healthy elderly. The findings warrant closer investigation about the cognitive effects of early dopamine-replacement therapy in neurological disorders. This trial was preregistered at the European Clinical Trial Registry, EudraCT#2016-000891-54 (2016-10-05).
To investigate whether coronary artery disease (CAD) burden is associated with plasma levels of the myocardial biomarkers Troponin I (TropI) and NT-proBNP in a large population-based sample using a cross-sectional design. Coronary computerized tomography (CT) angiography was performed in 25,859 subjects without a history of atherosclerotic disease from SCAPIS study (age 50-65, 52% women). TropI and NT-proBNP were measured in plasma. Segment involvement score (SIS) was the primary exposure and TropI the primary outcome. Both SIS and coronary artery calcium score, were associated with TropI levels following adjustment for age, sex and multiple confounders (p < 0.001), with similar relationships in men and women. Proximal segments from all three coronary arteries were related to TropI levels independently of one another. Adding TropI to traditional risk factors marginally increased discrimination of atherosclerosis as compared to risk factors alone (C-statistics + 0.0005, p = 0.014). SIS was related also to NT-proBNP levels, mainly in men, but with lower estimates than TropI. The burden of CAD was related to TropI levels in both men and women. All three major coronary arteries contributed to this relationship. Adding TropI to traditional risk factors resulted in only marginally improved discrimination of coronary atherosclerosis.
This study examined acute molecular responses to concurrent exercise involving different muscles. Eight men participated in a randomized crossover-trial with two sessions, one where they performed interval cycling followed by upper body resistance exercise (ER-Arm), and one with upper body resistance exercise only (R-Arm). Biopsies were taken from the triceps prior to and immediately, 90- and 180-min following exercise. Immediately after resistance exercise, the elevation in S6K1 activity was smaller and the 4E-BP1:eIF4E interaction greater in ER-Arm, but this acute attenuation disappeared during recovery. The protein synthetic rate in triceps was greater following exercise than at rest, with no difference between trials. The level of PGC-1α1 mRNA increased to greater extent in ER-Arm than R-Arm after 90 min of recovery, as was PGC-1α4 mRNA after both 90 and 180 min. Levels of MuRF-1 mRNA was unchanged in R-Arm, but elevated during recovery in ER-Arm, whereas MAFbx mRNA levels increased slightly in both trials. RNA sequencing in a subgroup of subjects revealed 862 differently expressed genes with ER-Arm versus R-Arm during recovery. These findings suggest that leg cycling prior to arm resistance exercise causes systemic changes that potentiate induction of specific genes in the triceps, without compromising the anabolic response.
The interplay between biomarkers of relevance to neuroplasticity and its association with learning and cognitive ability in old age remains poorly understood. The present study investigated acute changes in plasma concentrations of mature brain-derived neurotrophic factor (mBDNF), its precursor protein (pro-BDNF), and cortisol, in response to acute physical exercise and cognitive training interventions, their covariation and role in predicting cognitive performance. Confirmatory results provided no support for mBDNF, pro-BDNF and cortisol co-varying over time, as the acute interventions unfolded, but did confirm a positive association between mBDNF and pro-BDNF at rest. The confirmatory results did not support the hypothesis that mBDNF change following physical exercise were counteracted by temporally coupled changes in cortisol or pro-BDNF, or by cortisol at rest, in its previously demonstrated faciliatory effect on cognitive training outcome. Exploratory results instead provided indications of a general and trait-like cognitive benefit of exhibiting greater mBDNF responsiveness to acute interventions when coupled with lesser cortisol responsiveness, greater pro-BDNF responsiveness, and lower cortisol at rest. As such, the results call for future work to test whether certain biomarker profiles are associated with preserved cognition in old age.
Multidomain lifestyle interventions represents a promising strategy to counteract cognitive decline in older age. Brain-derived neurotrophic factor (BDNF) is essential for experience-dependent plasticity and increases following physical exercise, suggesting that physical exercise may facilitate subsequent learning. In a randomized-controlled trial, healthy older adults (65-75 years) completed a 12-week behavioral intervention that involved either physical exercise immediately before cognitive training (n = 25; 13 females), physical exercise immediately after cognitive training (n = 24; 11 females), physical exercise only (n = 27; 15 females), or cognitive training only (n = 21; 12 females). We hypothesized that cognition would benefit more from cognitive training when preceded as opposed to followed by physical exercise and that the relationship between exercise-induced increases in peripheral BDNF and cognitive training outcome would be greater when cognitive training is preceded by physical exercise. Greater increases of plasma BDNF were associated with greater cognitive training gains on trained task paradigms, but only when such increases preceded cognitive training (ß = 0.14, 95% CI [0.04, 0.25]). Average cognitive training outcome did not differ depending on intervention order (ß = 0.05, 95% CI [-0.10, 0.20]). The study provides the first empirical support for a time-critical but advantageous role for post-exercise increases in peripheral BDNF for learning at an interindividual level in older adults, with implications for future multidomain lifestyle interventions.
Blood-based biomarkers of neurodegeneration demonstrate great promise for the diagnosis and prognosis of Alzheimer's disease. Ultra-sensitive plasma assays now allow for quantification of the lower concentrations in cognitively unimpaired older adults, making it possible to investigate whether these markers can provide insight also into the early neurodegenerative processes that affect cognitive function and whether the markers are influenced by modifiable risk factors. Adopting an exploratory approach in 93 healthy older adults (65-75 years), we used structural equation modelling to investigate cross-sectional associations between multiple latent cognitive abilities (working memory, episodic memory, spatial and verbal reasoning) and plasma amyloid beta (Aβ42/Aβ40 ratio), phosphorylated-tau 181 (ptau-181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL), as well as the influence of device-measured habitual physical activity on these associations. The results showed that NfL was negatively associated with working memory, and that NfL interacted with moderate-to-vigorous physical activity in its association with episodic memory. The study has thereby demonstrated the potential of neurodegenerative plasma markers for improving understanding of normative cognitive aging and encourages future research to test the hypothesis that high levels of NfL, indicative of white matter pathology, limit the beneficial effect of physical activity on episodic memory in healthy aging.
VO2max (maximal oxygen consumption), a validated measure of aerobic fitness, has been associated with better cerebral artery compliance and measures of brain morphology, such as higher cortical thickness (CT) in frontal, temporal and cingular cortices, and larger grey matter volume (GMV) of the middle temporal gyrus, hippocampus, orbitofrontal cortex and cingulate cortex. Single sessions of physical exercise can promptly enhance cognitive performance and brain activity during executive tasks. However, the immediate effects of exercise on macro-scale properties of the brain's grey matter remain unclear. We investigated the impact of one session of moderate-intensity physical exercise, compared with rest, on grey matter volume, cortical thickness, working memory performance, and task-related brain activity in older adults. Cross-sectional associations between brain measures and VO2max were also tested. Exercise did not induce statistically significant changes in brain activity, grey matter volume, or cortical thickness. Cardiovascular fitness, measured by VO2max, was associated with lower grey matter blood flow in the left hippocampus and thicker cortex in the left superior temporal gyrus. Cortical thickness was reduced at post-test independent of exercise/rest. Our findings support that (1) fitter individuals may need lower grey matter blood flow to meet metabolic oxygen demand, and (2) have thicker cortex.
Increasing levels of physical inactivity is a global burden for mankind and is also an emerging problem in companion dogs. In both humans and dogs, insufficient physical activity is associated with increased risk for noncommunicable diseases and impaired quality of life (QoL). The aim of the current pilot study was to evaluate effects of a joint outdoor exercise program for dog owners (n = 22) and dogs (n = 22) with focus on QoL and body measurements. Results indicate that an eight-week exercise intervention alone, with a target distance of at least 2 km twice a week, may be sufficient to significantly increase self-reported QoL and acceptance of bodily appearance in dog owners despite no reductions in body measurements. In dogs, a significantly reduced body condition score (BCS) was registered, despite no considerable changes in feeding. The increased owner motivation for continued joint exercise suggests potential for lifestyle changes, which could be investigated in future studies including control groups and long-term follow-ups. The importance of the human-animal bond as a success factor for increased mutual physical activity and health benefits in both dog owners and dogs is recommended to be studied in a more in-depth manner.
Sickness absence from work has a large adverse impact on both individuals and societies in Sweden and the costs for sickness absence were calculated to 64.6 billion Swedish kronor (approx. 5.6 billion in Euros) in 2020. Although high cardiorespiratory fitness may protect against potential adverse effects of high physical workload, research on the moderating effect of respiratory fitness in the relation between having an occupation with high physical workload and sickness absence is scarce. To study the moderating effect of cardiorespiratory fitness in the association between occupation and psychiatric, musculoskeletal, and cardiorespiratory diagnoses. Data was retrieved from the HPI Health Profile Institute database (1988-2020) and Included 77,366 participants (mean age 41.8 years, 52.5% women) from the Swedish workforce. The sample was chosen based on occupational groups with a generally low education level and differences in physical workload. Hurdle models were used to account for incident sickness absence and the rate of sickness absence days. There were differences in sickness absence between occupational groups for musculoskeletal and cardiorespiratory diagnoses, but not for psychiatric diagnoses. In general, the association between occupation and musculoskeletal and cardiorespiratory diagnoses was moderated by cardiorespiratory fitness in most occupational groups with higher physical workload, whereas no moderating effect was observed for psychiatric diagnoses. The study results encourage community and workplace interventions to both consider variation in physical workload and to maintain and/or improve cardiorespiratory fitness for a lower risk of sickness absence, especially in occupations with high physical workload.
Knowledge about the orientation of a representative ankle joint axis is limited to studies of tarsal morphology and of quasistatic movements. The aim of our study was therefore to determine the development of the axis orientation during walking. Intracortical bone pins were used to monitor the kinematics of the talus and tibia of five healthy volunteers. The finite helical axis was determined for moving windows of 10% stance phase and its orientation reported if the rotation about the axis was more than 2°. A representative axis for ankle dorsi- and plantarflexion was also estimated based on tarsal morphology. As reported by literature, the morphology-based axis was inclined more medially upwards for dorsiflexion than for plantarflexion. However, when a mean of the finite helical axis orientations was calculated for each walking trial for dorsiflexion (stance phase 15-25%) and for plantarflexion (stance phase 85-95%), the inclination was less medially upwards in dorsiflexion than in plantarflexion in four out of five participants. Thus, it appears that the inclination of a representative ankle joint axis for dynamic loading situations cannot be estimated from either morphology or quasi-static experiments. Future studies assessing muscle activity, ligament behaviour and articulating surfaces may help to identify the determining factors for the orientation of a representative ankle joint axis.