Stroke volume response during prolonged exercise depends on left ventricular filling: evidence from a ß-blockade study.

Prolonged moderate-intensity exercise leads to a progressive upward drift in heart rate (HR) that may compromise stroke volume (SV). Alternatively, the HR drift may be related to abated SV due to impaired ventricular function. The aim of this study was to examine the effects of cardiovascular drift on left ventricular volumes and in turn SV. Thirteen healthy young males completed two 60-min cycling bouts on a semirecumbent cycle ergometer at 57% maximal oxygen consumption (V̇o2max) either under placebo condition (CON) or after ingesting a small dose of ß1-blockers (BB). Measurements of HR, end-diastolic volume (EDV), and end-systolic volume were obtained by echocardiography and used to calculate SV. Other variables such as ear temperature, skin temperature, blood pressure, and blood volume were measured to assess potential changes in thermoregulatory needs and loading conditions. HR drift was successfully prevented when using BB from min 10 to min 60 (128 ± 9 to 126 ± 8 beats/min, P = 0.29) but not in CON (134 ± 10 to 148 ± 10 beats/min, P < 0.01). Conversely, during the same time, SV increased by 13% when using BB (103 ± 9 to 116 ± 7 mL, P < 0.01), whereas it was unchanged in CON (99 ± 7 to 101 ± 9 mL, P = 0.37). The SV behavior was mediated by a 4% increase in EDV in the BB condition (164 ± 18 to 170 ± 18 mL, P < 0.01), whereas no change was observed in the CON condition (162 ± 18 to 160 ± 18 mL, P = 0.23). In conclusion, blocking HR drift enhances EDV and SV during prolonged exercise. These findings suggest that SV behavior is tightly related to filling time and loading conditions of the left ventricle.

PoseEdit: enhanced ligand binding mode communication by interactive 2D diagrams.

In this article, we present PoseEdit, a new, interactive frontend of the popular pose visualization tool PoseView. PoseEdit automatically produces high-quality 2D diagrams of intermolecular interactions in 3D binding sites calculated from ligands in complex with protein, DNA, and RNA. The PoseView diagrams have been improved in several aspects, most notably in their interactivity. Thanks to the easy-to-use 2D editor of PoseEdit, the diagrams are extensively editable and extendible by the user, can be merged with other diagrams, and even be created from scratch. A large variety of graphical objects in the diagram can be moved, rotated, selected and highlighted, mirrored, removed, or even newly added. Furthermore, PoseEdit enables a synchronized 2D-3D view of macromolecule-ligand complexes simplifying the analysis of structural features and interactions. The representation of individual diagram objects regarding their visualized chemical properties, like stereochemistry, and general graphical styles, like the color of interactions, can additionally be edited. The primary objective of PoseEdit is to support scientists with an enhanced way to communicate ligand binding mode information through graphical 2D representations optimized with the scientist's input in accordance with objective criteria and individual needs. PoseEdit is freely available on the ProteinsPlus web server ( https://proteins.plus ).

Maximal strength training in patients with inflammatory rheumatic disease: implications for physical function and quality of life.

PURPOSE: Patients with inflammatory rheumatic disease (IRD) have attenuated muscle strength in the lower extremities, resulting in impaired physical function and quality of life. Although maximal strength training (MST), applying heavy resistance, is documented to be a potent countermeasure for such attenuation, it is uncertain if it is feasible in IRD given the pain, stiffness, and joint swelling that characterize the population. METHODS: 23 patients with IRD (49 ± 13 years; 20 females/3 males), diagnosed with spondyloarthritis, rheumatoid arthritis, or systemic lupus erythematosus, were randomized to MST or a control group (CG). The MST group performed four × four repetitions dynamic leg press two times per week for 10 weeks at ~ 90% of one repetition maximum (1RM). Before and after training 1RM, rate of force development (RFD), and health-related quality of life (HRQoL) were measured. RESULTS: Session attendance in the MST group was 95%, of which 95% conducted according to MST protocol. Furthermore, MST increased 1RM (29 ± 12%, p = 0.001) and early and late phase RFD (33-76%, p < 0.05). All improvements were different from the CG (p < 0.05). MST also resulted in HRQoL improvements in the dimensions; physical functioning, general health, and vitality (p < 0.05). Physical functioning was associated with 1RM (rho = 0.55, p < 0.01) and early phase RFD (rho = 0.53-0.71, p < 0.01; different from CG p < 0.05). CONCLUSIONS: Despite being characterized by pain, stiffness, and joint swelling, patients with IRD appear to tolerate MST well. Given the improvements in 1RM, RFD, and HRQoL MST should be considered as a treatment strategy to counteract attenuated muscle strength, physical function, and HRQoL. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04998955, retrospectively registered.

Maximal strength training-induced improvements in forearm work efficiency are associated with reduced blood flow.

Maximal strength training (MST) improves work efficiency. However, since blood flow is greatly dictated by muscle contractions in arms during exercise and vascular conductance is lower, it has been indicated that arms rely more upon adapting oxygen extraction than legs in response to the enhanced work efficiency. Thus, to investigate if metabolic and vascular responses are arm specific, we used Doppler-ultrasound and a catheter placed in the subclavian vein to measure blood flow and the arteriovenous oxygen difference during steady-state work in seven young men [24 ± 3 (SD) yr] following 6 wk of handgrip MST. As expected, MST improved maximal strength (49 ± 9 to 62 ± 10 kg) and the rate of force development (923 ± 224 to 1,086 ± 238 N/s), resulting in a reduced submaximal oxygen uptake (30 ± 9 to 24 ± 10 ml/min) and concomitantly increased work efficiency (9.3 ± 2.5 to 12.4 ± 3.9%) (all P < 0.05). In turn, the work efficiency improvement was associated with reduced blood flow (486 ± 102 to 395 ± 114 ml/min), mediated by a lower blood velocity (43 ± 8 to 32 ± 6 cm/s) (all P < 0.05). Conduit artery diameter and the arteriovenous oxygen difference remained unaltered. The maximal work test revealed an increased time to exhaustion (949 ± 239 to 1,102 ± 292 s) and maximal work rate (both P < 0.05) but no change in peak oxygen uptake. In conclusion, despite prior indications of metabolic and vascular limb-specific differences, these results reveal that improved work efficiency after small muscle mass strength training in the upper extremities is accompanied by a blood flow reduction and coheres with what has been documented for lower extremities. NEW & NOTEWORTHY Maximal strength training increases skeletal muscle work efficiency. Oxygen extraction has been indicated to be the adapting component with this increased work efficiency in arms. However, we document that decreased blood flow, achieved by blood velocity reduction, is the adapting mechanism responding to the improved aerobic metabolism in the forearm musculature.

Cysteine deprivation prevents induction of peroxisome proliferator-activated receptor gamma-2 and adipose differentiation of 3T3-L1 cells.

Plasma cysteine is strongly associated with body fat mass in human cohorts and diets low in cysteine prevents fat accumulation in mice. It is unclear if plasma cysteine affects fat development or if fat accumulation raises plasma cysteine. To determine if cysteine affects adipogenesis, we differentiated 3T3-L1 preadipocytes in medium with reduced cysteine. Cells incubated in media with 10-20µM cysteine exhibited reduced capacity to differentiate into triacylglycerol-storing mature adipocytes compared with cells incubated with 50µM cysteine. Low cysteine severely reduced expression of peroxisome proliferator-activated receptor gamma2 (Pparγ2) and its target genes perlipin1 (Plin1) and fatty acid binding protein-4 (Fabp4). Expression of stearoyl-CoA desaturase-1 (Scd1), known to be repressed with cysteine depletion, was also reduced with low cysteine. Medium depletion of the essential amino acids leucine, valine, and isoleucine had only a modest effect on adipocyte specific gene expression and differentiation. Stimulation with the PPARγ agonist BRL-49653 or addition of a hydrogen sulfide donor enhanced differentiation of 3T3-L1 cells cultured in low cysteine. This demonstrates that the ability to induce PPARγ expression is preserved when cells are cultured in low cysteine. It therefore appears that cysteine depletion inhibits adipogenesis by specifically affecting molecular pathways required for induction of PPARγ expression, rather than through a general reduction of global protein synthesis. In conclusion, we show that low extracellular cysteine reduces adipocyte differentiation by interfering with PPARγ2 and PPARγ target gene expression. Our results provide further evidence for the hypothesis that plasma cysteine is a casual determinant for body fat mass.

Fatty acids regulate perilipin5 in muscle by activating PPARδ.

The surface of lipid droplets (LDs) in various cell types is coated with perilipin proteins encoded by the Plin genes. Perilipins regulate LD metabolism by selectively recruiting lipases and other proteins to LDs. We have studied the expression of perilipins in mouse muscle. The glycolytic fiber-enriched gastrocnemius muscle expresses predominantly Plin2-4. The oxidative fiber-enriched soleus muscle expresses Plin2-5. Expression of Plin2 and Plin4-5 is elevated in gastrocnemius and soleus muscles from mice fed a high-fat diet. This effect is preserved in peroxisome proliferator-activated receptor (PPAR)α-deficient mice. Mouse muscle derived C2C12 cells differentiated into glycolytic fibers increase transcription of these Plins when exposed to various long chain fatty acids (FAs). To understand how FAs regulate Plin genes, we used specific activators and antagonists against PPARs, Plin promoter reporter assays, chromatin immunoprecipitation, siRNA, and animal models. Our analyses demonstrate that FAs require PPARδ to induce transcription of Plin4 and Plin5. We further identify a functional PPAR binding site in the Plin5 gene and establish Plin5 as a novel direct PPARδ target in muscle. Our study reveals that muscle cells respond to elevated FAs by increasing transcription of several perilipin LD-coating proteins. This induction renders the muscle better equipped to sequester incoming FAs into cytosolic LDs.

Aging increases metabolic capacity and reduces work efficiency during handgrip exercise in males.

Maximal oxygen uptake and exercise performance typically decline with age. However, there are indications of preserved vascular function and blood flow regulation during arm exercise. Yet, it is unknown if this potential physiological preservation with age is mirrored in peripheral metabolic capacity and V̇o2/W ratio. Thus, to investigate the effects of aging in the arms, we measured metabolic and vascular responses to 6-min bouts of dynamic handgrip exercise at 40% and 80% of maximal work rate (WRmax) in 11 young (26 ± 2 yr) and 12 old (80 ± 6 yr) males, applying Doppler-ultrasound combined with blood samples from a deep forearm vein. At baseline, the old had a larger arterial diameter compared with young (P < 0.001). During exercise, the two groups reached the same WRmax. V̇o2, blood flow, and oxygen supply were higher (40%WRmax; 80%WRmax, all P < 0.01), and arteriovenous oxygen difference was lower (80%WRmax, P < 0.02), in old compared with young. Old also had a higher oxygen excess at 80%WRmax (P < 0.01) than young, whereas no difference in muscle diffusion or oxygen extraction was detected. Only young exhibited an increase in intensity-induced arterial dilation (P < 0.05), and they had a lower mean arterial pressure than old at 80%WRmax (P < 0.001). V̇o2/W (40%WRmax; 80%WRmax) was reduced in old compared with young (both P < 0.05). In conclusion, in old and young males with a similar handgrip WRmax, old had a higher V̇o2 during 80%WRmax intensity, achieved by an increased blood flow. This may be a result of the available cardiac output reserve, compensating for reduced work efficiency and attenuated vascular response observed in old.NEW & NOTEWORTHY Contrasting the typically observed decline in V̇o2max with age, the current study reveals an age-related increase in forearm metabolic capacity during handgrip exercise in old, mediated by an increased forearm blood flow. Exercise with a small muscle mass in arms, where central components of the oxygen transport are not limiting, allows old to attain a similar maximal work rate as young despite their increased V̇o2/W ratio.

Strength versus endurance trained master athletes: Contrasting neurophysiological adaptations.

Neural factors play a critical role in the age-related decline in maximal strength and rate of force development (RFD). However, it is uncertain how the age-related attenuation in neuromuscular function may be mitigated in strength or endurance trained master athletes. In this study we applied evoked spinal motoneuron recordings to examine descending motor drive, i.e., efferent drive from supraspinal and spinal centres during maximal voluntary contraction (MVC; V-wave) and H-reflex excitability measured at 10 % MVC in older (>65 yrs) and younger (<35 yrs) strength athletes (n = 21), endurance athletes (n = 17) and untrained control participants (n = 30). Both strength (b = 0.09 [0.01-0.18], p = 0.038) and endurance training (b = 0.14 [0.04-0.23], p = 0.006) were associated with a high V-wave amplitude. This was likely explained by an elevated H-reflex excitability (b = 0.23 [0.11-0.35], p < 0.001) in endurance trained participants, which failed to be seen in strength trained participants. These contrasting neurophysiological properties were accompanied by different physiological traits; strength training was associated with high maximal strength (b = 107.5 [84.6 to 130.4] kg, p < 0.001) and RFD (b = 3171 [2248 to 4094] N‧s-1, p < 0.001), whereas endurance training was associated with elevated maximal oxygen uptake (V̇O2max; b = 13.6 [8.0-19.2] ml‧kg-1‧min-1, p < 0.001). This pattern was apparent irrespective of age, although all traits were negatively associated with advanced age (p < 0.05). In conclusion, strength trained individuals demonstrate higher descending motor drive (elevated V-wave responses), compared to age-matched untrained individuals. Endurance trained individuals also showed elevated V-wave responses, uniquely accompanied by enhanced α-motoneuron excitability and/or reduced pre/postsynaptic inhibition (elevated H-reflex responses). Since a high descending motor drive is a key component of strong muscle contractions, strength training should be emphasized to sustain the ability to carry out force-dependent tasks at older age.

The impact of life-long strength versus endurance training on muscle fiber morphology and phenotype composition in older men.

Aging is typically associated with decreased muscle strength and rate of force development (RFD), partly explained by motor unit remodeling due to denervation, and subsequent loss of fast-twitch type II myofibers. Exercise is commonly advocated to counteract this detrimental loss. However, it is unclear how life-long strength versus endurance training may differentially affect markers of denervation and reinnervation of skeletal myofibers and, in turn, affect the proportion and morphology of fast-twitch type II musculature. Thus, we compared fiber type distribution, fiber type grouping, and the prevalence of atrophic myofibers (≤1,494 µm2) in strength-trained (OS) versus endurance-trained (OE) master athletes and compared the results to recreationally active older adults (all >70 yr, OC) and young habitually active references (<30 yr, YC). Immunofluorescent stainings were performed on biopsy samples from vastus lateralis, along with leg press maximal strength and RFD measurements. OS demonstrated similar type II fiber distribution (OS: 52.0 ± 16.4%; YC: 51.1 ± 14.4%), fiber type grouping, maximal strength (OS: 170.0 ± 18.9 kg, YC: 151.0 ± 24.4 kg), and RFD (OS: 3,993 ± 894 N·s-1, YC: 3,470 ± 1,394 N·s-1) as young, and absence of atrophic myofibers (OS: 0.2 ± 0.7%; YC: 0.1 ± 0.4%). In contrast, OE and OC exhibited more atrophic fibers (OE: 1.2 ± 1.0%; OC: 1.1 ± 1.4%), more grouped fibers, and smaller proportion of type II fibers (OE: 39.3 ± 11.9%; OC: 35.0 ± 12.4%) than OS and YC (all P < 0.05). In conclusion, strength-trained master athletes were characterized by similar muscle morphology as young, which was not the case for recreationally active or endurance-trained old. These results indicate that strength training may preserve type II fibers with advancing age in older men, likely as a result of chronic use of high contractile force generation.NEW & NOTEWORTHY Aging is associated with loss of fast-twitch type II myofibers, motor unit remodeling, and grouping of myofibers. This study reveals, for the first time, that strength training preserves neural innervation of type II fibers, resulting in similar myofiber type distribution and grouping in life-long strength-trained master athletes as young moderately active adults. In contrast, life-long endurance-trained master athletes and recreationally active old adults demonstrated higher proportion of type I fibers accompanied by more marked grouping of type I myofibers, and more atrophic fibers compared with strength-trained master athletes and young individuals. Thus, strength training should be utilized as a training modality for preservation of fast-twitch musculature, maximal muscle strength, and rapid force capacity (RFD) with advancing age.

Direct and indirect climatic drivers of biotic interactions: ice-cover and carbon runoff shaping Arctic char Salvelinus alpinus and brown trout Salmo trutta competitive asymmetries.

One of the major challenges in ecological climate change impact science is to untangle the climatic effects on biological interactions and indirect cascading effects through different ecosystems. Here, we test for direct and indirect climatic drivers on competitive impact of Arctic char (Salvelinus alpinus L.) on brown trout (Salmo trutta L.) along a climate gradient in central Scandinavia, spanning from coastal to high-alpine environments. As a measure of competitive impact, trout food consumption was measured using (137)Cs tracer methodology both during the ice-covered and ice-free periods, and contrasted between lakes with or without char coexistence along the climate gradient. Variation in food consumption between lakes was best described by a linear mixed effect model including a three-way interaction between the presence/absence of Arctic char, season and Secchi depth. The latter is proxy for terrestrial dissolved organic carbon run-off, strongly governed by climatic properties of the catchment. The presence of Arctic char had a negative impact on trout food consumption. However, this effect was stronger during ice-cover and in lakes receiving high carbon load from the catchment, whereas no effect of water temperature was evident. In conclusion, the length of the ice-covered period and the export of allochthonous material from the catchment are likely major, but contrasting, climatic drivers of the competitive interaction between two freshwater lake top predators. While future climatic scenarios predict shorter ice-cover duration, they also predict increased carbon run-off. The present study therefore emphasizes the complexity of cascading ecosystem effects in future effects of climate change on freshwater ecosystems.

Smartphone-Assisted High-Intensity Interval Training in Inflammatory Rheumatic Disease Patients: Randomized Controlled Trial.

BACKGROUND: Patients with inflammatory rheumatic diseases (IRDs) experience disease-related barriers to physical training. Compared with the general population, IRD patients are reported to have reduced maximal oxygen uptake (VO2max) and physical activity levels. Supervised high-intensity interval training (HIIT) is documented to counteract the reduced VO2max and poor cardiovascular health associated with IRDs. However, supervised HIIT is resource demanding. OBJECTIVE: This study sought to investigate if self-administered 4×4-min HIIT guided by a smartphone app (Myworkout GO) could yield similar HIIT-induced effects as standard 4×4-min HIIT performed under the guidance and supervision of health care professionals. The effects studied were on VO2max and health-related quality of life (HRQoL). METHODS: Forty patients (33 female patients, mean age 48 years, SD 12 years; 7 male patients, mean age 52 years, SD 11 years) diagnosed with rheumatoid arthritis, spondyloarthritis, or systemic lupus erythematosus were randomized to a supervised group (SG) or an app group (AG). Both groups were instructed to perform 4×4-min intervals with a rate of perceived exertion of 16 to 17, corresponding to 85% to 95% of the maximal heart rate, twice a week for 10 weeks. Treadmill VO2max and HRQoL measured using RAND-36 were assessed before and after the exercise period. RESULTS: VO2max increased (P<.001) in both groups after 10 weeks of HIIT, with improvements of 3.6 (SD 1.3) mL/kg/min in the SG and 3.7 (SD 1.5) mL/kg/min in the AG. This was accompanied by increases in oxygen pulse in both groups (P<.001), with no between-group differences apparent for either measure. Improvements in the HRQoL dimensions of bodily pain, vitality, and social functioning were observed for both groups (P<.001 to P=.04). Again, no between-group differences were detected. CONCLUSIONS: High-intensity 4×4-min interval training increased VO2max and HRQoL, contributing to patients' reduced cardiovascular disease risk, improved health and performance, and enhanced quality of life. Similar improvements were observed following HIIT when IRD patients were guided using perceived exertion by health care professionals or the training was self-administered and guided by the app Myworkout GO. Utilization of the app may help reduce the cost of HIIT as a treatment strategy in this patient population. TRIAL REGISTRATION: ClinicalTrials.gov NCT04649528; https://clinicaltrials.gov/ct2/show/NCT04649528.

Early Maximal Strength Training Improves Leg Strength and Postural Stability in Elderly Following Hip Fracture Surgery.

INTRODUCTION: Hip fractures predominantly occur in the geriatric population and results in increased physical inactivity and reduced independency, largely influenced by a downward spiral of ambulatory capacity, related to loss of skeletal muscle strength and postural stability. Thus, effective postoperative treatment, targeting improvements in muscle strength, is sought after. MATERIALS & METHODS: Twenty-one hip fracture patients (>65 yr) were randomized to 8 weeks of either conventional physiotherapy control group (CG), or leg press and hip abduction maximal strength training (MST) 3 times per week. MST was performed applying heavy loads (85-90% of 1 repetition maximum; 1RM) and 4-5 repetitions in 4 sets. Maximal strength (bi- and unilateral 1RM), postural stability (unipedal stance test; UPS), and DEXA-scan bone mineral content/ density (BMC/BMD) were measured before and after the 8-week rehabilitation. RESULTS: Both MST and conventional physiotherapy improved bilateral leg press 1RM by 41 ± 27 kg and 29 ± 17 kg, respectively (both p < 0.01), while unilateral leg press 1RM only increased after MST (within group and between groups difference: both p < 0.05). MST also resulted in an increase in abduction 1RM in both the fractured (5 kg, 95%CI: 2-7; p < 0.01) and healthy limb (6 kg, 95%CI: 3-9; p < 0.01), while no such improvement was apparent in the CG (between groups difference: p < 0.01). Finally, MST improved UPS of the fractured limb (p < 0.05). No differences were observed in BMC or BMD following the 8 weeks. DISCUSSION: Early postoperative MST improved lower extremities maximal muscle strength more than conventional physiotherapy and was accompanied by improvements in postural stability. CONCLUSION: Implementing MST in early rehabilitation after hip fracture surgery should be considered as a relevant treatment to curtail the downward spiral of reduced ambulatory capacity typical for this patient group, possibly reducing the risk of recuring falls and excess mortality. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03030092.

High-Intensity Shoulder Abduction Exercise in Subacromial Pain Syndrome.

Subacromial pain syndrome (SAPS) defined as pain of nontraumatic origin localized around the acromion, is a debilitating, common, and often chronic condition. Among many proposed underlying causes of SAPS, hypoperfusion and hypoxic conditions in and around the tendons may be an intrinsic cause of SAPS. PURPOSE: This study aimed to determine if adding high-intensity aerobic interval training (HIIT) of the rotator cuff to usual care was feasible in SAPS and improved shoulder endurance more than usual care alone, as well as to examine the influence on shoulder pain and disability and the response of tendinous microcirculation after HIIT. METHODS: Twenty-one subjects with chronic SAPS were randomized to two groups: experimental group (EG; n = 13) receiving HIIT in addition to treatment as usual and control group (CG; n = 8) receiving treatment as usual. Before and after 8 wk of exercise therapy, endurance performance was assessed by an incremental abduction exercise of the arm to exhaustion (TTE). Pain and disability was assessed by the shoulder pain and disability index (SPADI). Contrast-enhanced ultrasound of the musculus supraspinatus and tendon was utilized to indicate tendon blood flow. RESULTS: Endurance in the TTE test improved by an estimated 233 s more on average in EG than in CG (P = 0.001; 95% confidence interval, 102 to 363). The SPADI score was reduced 22 points more on average in EG (P = 0.017; 95% confidence interval, -40 to -5). The change from pretest to posttest was significant in EG for both TTE test and SPADI improvement (P < 0.001). EG also experienced less pain during exercise after the intervention compared with CG (P < 0.001). Contrast-enhanced ultrasound indicated an increase in tendinous blood flow in EG (P = 0.019). CONCLUSIONS: HIIT rotator cuff exercise seems to be a feasible intervention in SAPS, increasing endurance performance more than usual care alone.

Versatile high-pressure gas apparatus for benchtop NMR: Design and selected applications.

A simple, yet highly versatile setup is presented for benchtop NMR analyses of gases at high-pressure. It consists mostly of commercial parts and includes multiple safety features while maintaining a small size to fit into a 1.20 m wide fume hood. Pressures up to 200 bar can be adjusted independently of the sample gas-bottle pressure in a matter of seconds. Mixtures of multiple gases can be produced in situ in a mixing chamber, which also serves to adjust the pressure. The high-pressure hardware and benchtop NMR spectrometer have been tested for long-term stability and repeatability of the measurements. The versatility of the setup is demonstrated by analyzing hydrocarbon-gas with attention to linewidths as well as their 1H relaxation times, by improving the resolution of 1H NMR spectra from solid polymers with pressurized CO2, and by visualizing the ingress of gaseous and supercritical methane into liquid benzene.

IL-7 is expressed and secreted by human skeletal muscle cells.

In addition to generating movement, skeletal muscle may have a function as a secretory organ. The aim of the present study was to identify novel proteins with signaling capabilities secreted from skeletal muscle cells. IL-7 was detected in media conditioned by primary cultures of human myotubes differentiated from satellite cells, and concentrations increased with incubation time. By immunoblotting and real-time RT-PCR IL-7 expression was confirmed at both protein and mRNA levels. Furthermore, with immunofluorescence and specific antisera, multinucleated myotubes were found to coexpress IL-7 and myosin heavy chain. During differentiation of human myotubes from satellite cells, IL-7 expression increased at mRNA and protein levels. In contrast, mRNA expression of the IL-7 receptor was 80% lower in myotubes compared with satellite cells. Incubations with recombinant IL-7 under differentiation conditions caused approximately 35% reduction in mRNA for the terminal myogenic markers myosin heavy chain 2 (MYH2) and myogenin (MYOG), suggesting that IL-7 may act on satellite cells to inhibit development of the muscle fiber phenotype. Alternative routes of cell development were investigated, and IL-7 increased migration of satellite cells by 40% after 48 h in a Transwell system, whereas cell proliferation remained unchanged. In vivo, real-time RT-PCR analysis of musculus vastus lateralis (n = 10) and musculus trapezius (n = 7) biopsies taken from male individuals undergoing a strength training program demonstrated that after 11 wk mean IL-7 mRNA increased by threefold (P = 0.01) and fourfold (P = 0.04), respectively. In conclusion, we have demonstrated that IL-7 is a novel myokine regulated both in vitro and in vivo, and it may play a role in the regulation of muscle cell development.

Adaptive winter survival strategies: defended energy levels in juvenile Atlantic salmon along a latitudinal gradient.

Current knowledge suggests that patterns of energy storage and depletion in animals are governed by behavioural trade-offs between risks associated with feeding and future energy demands. However, the length of adverse periods varies over geographical or climatic gradients. To explore the potential for genotypic sources of variation in behavioural trade-offs, we compared the winter energy-depletion patterns among 13 wild populations of juvenile Atlantic salmon (Salmo salar L.) along a latitudinal gradient (58-70 degrees N) and performed common-environment experiments of energy-state-dependent feeding. In the wild, winter lipid-depletion rates were lower for northern than for southern populations. The variation in spring lipid levels among the population was lower than autumn variation, with storage lipid levels clustered close to critical limits for survival. In semi-natural stream channels with natural food supply, hatchery-reared fish originating from northern populations showed a positive scaling of feeding activity with decreasing energy levels, whereas southern populations did not. In conclusion, juvenile Atlantic salmon from northern populations defend their energy levels more strongly than fish from southern populations. Adaptive variation in feeding activity appears important for this difference. Thus, the present study shows a link between geographical patterns in storage energy trajectories and adaptive differences in state-dependent feeding motivation.

Medicine and interest politics a study of decision-making processes in the area of vascular surgery in Norway.

PURPOSE: The purpose of this paper is to increase the understanding of organizational challenges when decision-makers try to comply with technological developments and increasing demands for a more rational distribution of health care services. This paper explores two decision-making processes from 2007-2019 in the area of vascular surgery at a regional and a local level in Norway. DESIGN/METHODOLOGY/APPROACH: The study draws upon extensive document analyses, semi-structured interviews and field conversations. The empirical material was analyzed in several steps through an inductive approach and described and explained through a theoretical framework based on rational choice (i.e. bounded rationality), political behavior and institutionalism. These perspectives were used in a complementary way. FINDINGS: Both decision-making processes were resource-intensive, long-lasting and produced few organizational changes for the provision of vascular services. Stakeholders at both levels outmaneuvered the health care planners, though by different means. Regionally, the decision-making ended up in a political process, while locally the decision-making proceeded as a strategic game between different departments and professional fields. PRACTICAL IMPLICATIONS: Decision-makers need to prepare thoroughly for convincing others of the benefits of new ways of organizing clinical care. By providing meaningful opportunities for public involvement, by identifying and anticipating political agendas and by building alliances between stakeholders with divergent values and aims decision-makers may extend the realm of feasible solutions. ORIGINALITY/VALUE: This paper contributes to the understanding of why decision-making processes can be particularly challenging in a field characterized by rapid technological development, new treatment options and increasing demands for more rational distribution of services.

Skeletal Muscle Mitochondrial Adaptations to Maximal Strength Training in Older Adults.

Maximal strength training (MST) results in robust improvements in skeletal muscle force production, efficiency, and mass. However, the effects of MST on muscle mitochondria are still unknown. Accordingly, the purpose of this study was to examine, from the molecular level to whole-muscle, mitochondrial adaptations induced by 8 weeks of knee-extension MST in the quadriceps of 10 older adults using immunoblotting, spectrophotometry, high-resolution respirometry in permeabilized muscle fibers, in vivo 31P magnetic resonance spectroscopy (31P-MRS), and gas exchange. As anticipated, MST resulted in an increased isometric knee-extensor force from 133 ± 36 to 147 ± 49 Nm (p < .05) and quadriceps muscle volume from 1,410 ± 103 to 1,555 ± 455 cm3 (p < .05). Mitochondrial complex (I-V) protein abundance and citrate synthase activity were not significantly altered by MST. Assessed ex vivo, maximal ADP-stimulated respiration (state 3CI+CII, PRE: 23 ± 6 and POST: 14 ± 5 ρM·mg-1·s-1, p < .05), was decreased by MST, predominantly, as a result of a decline in complex I-linked respiration (p < .05). Additionally, state 3 free-fatty acid linked respiration was decreased following MST (PRE: 19 ± 5 and POST: 14 ± 3 ρM·mg-1·s-1, p < .05). Assessed in vivo, MST slowed the PCr recovery time constant (PRE: 49 ± 13 and POST: 57 ± 16 seconds, p < .05) and lowered, by ~20% (p = .055), the quadriceps peak rate of oxidative ATP synthesis, but did not significantly alter the oxidation of lipid. Although these, likely qualitative, mitochondrial adaptations are potentially negative in terms of skeletal muscle energetic capacity, they need to be considered in light of the many improvements in muscle function that MST affords older adults.

The Non-linear Electrical Properties of Silver/silver Chloride Electrodes in Sodium Chloride Solution.

An electrical measurement is non-linear when it is affected by the applied stimulus, i.e. when the measured phenomenon changes with amplitude. If pinched hysteresis loops can be observed in the voltage current representation, the underlying tissue can be classified as a memristor. Several biological memristors have been published, like human skin and apples. However, changes in the polarization impedance of electrodes may also cause pinched hysteresis loops. The question whether the reported biological memristors are real or whether the results just reflect changes in the polarization impedance arises. If the impedance of the measured object is close to or smaller than the polarization impedance of the used electrodes, the latter may dominate the measurement. In this study, we investigated the non-linear electrical properties of silver/silver chloride electrodes in a sodium chloride solution that has a similar concentration as human sweat and compared these to results from human skin. First of all, we found that silver/silver chloride electrodes in sodium chloride solution can be classified as memristors. However, the currents obtained from the sodium chloride solution are much higher than the currents recorded from human skin and there is a qualitative difference in the pinched hysteresis loops in both cases. We can conclude that the non-linear electrical measurements with silver/silver chloride on human skin are actually dominated by the skin and we can confirm that the human skin memristor really exists.