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  • 1. Adiels, Martin
    et al.
    Mardinoglu, Adil
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Chalmers University of Technology, Sweden.
    Taskinen, Marja-Riitta
    Boren, Jan
    Kinetic Studies to Elucidate Impaired Metabolism of Triglyceride-rich Lipoproteins in Humans2015In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 6, article id 342Article, review/survey (Refereed)
    Abstract [en]

    To develop novel strategies for prevention and treatment of dyslipidemia, it is essential to understand the pathophysiology of dyslipoproteinemia in humans. Lipoprotein metabolism is a complex system in which abnormal concentrations of various lipoprotein particles can result from alterations in their rates of production, conversion, and/or catabolism. Traditional methods that measure plasma lipoprotein concentrations only provide static estimates of lipoprotein metabolism and hence limited mechanistic information. By contrast, the use of tracers labeled with stable isotopes and mathematical modeling, provides us with a powerful tool for probing lipid and lipoprotein kinetics in vivo and furthering our understanding of the pathogenesis of dyslipoproteinemia.

  • 2.
    Andersson, Erik
    et al.
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Govus, Andrew
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. La Trobe University, Melbourne, VIC, Australia.
    Shannon, Oliver Michael
    Newcastle University, Newcastle upon Tyne, United Kingdom.
    McGawley, Kerry
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Sex differences in performance and pacing strategies during sprint skiing2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 295Article in journal (Refereed)
    Abstract [en]

    Purpose: This study aimed to compare performance and pacing strategies between elite male and female cross-country skiers during a sprint competition on snow using the skating technique.

    Methods: Twenty male and 14 female skiers completed an individual time-trial prolog (TT) and three head-to-head races (quarter, semi, and final) on the same 1,572-m course, which was divided into flat, uphill and downhill sections. Section-specific speeds, choice of sub-technique (i.e., gear), cycle characteristics, heart rate and post-race blood lactate concentration were monitored. Power output was estimated for the different sections during the TT, while metabolic demand was estimated for two uphill camera sections and the final 50-m flat camera section.

    Results: Average speed during the four races was ∼12.5% faster for males than females (P < 0.001), while speeds on the flat, uphill and downhill sections were ∼11, 18, and 9% faster for the males than females (all P< 0.001 for terrain, sex, and interaction). Differences in uphill TT speed between the sexes were associated with different sub-technique preferences, with males using a higher gear more frequently than females (P < 0.05). The estimated metabolic demand relative to maximal oxygen uptake (V&#x2D9;" role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; outline: 0px !important;">V˙V˙O2max) was similar for both sexes during the two uphill camera sections (∼129% of V&#x2D9;" role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; outline: 0px !important;">V˙V˙O2max) and for the final 50-m flat section (∼153% of V&#x2D9;" role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; outline: 0px !important;">V˙V˙O2max). Relative power output during the TT was 18% higher for males compared to females (P < 0.001) and was highly variable along the course for both sexes (coefficient of variation [CV] between sections 4–9 was 53%), while the same variation in heart rate was low (CV was ∼3%). The head-to-head races were ∼2.4% faster than the TT for both sexes and most race winners (61%) were positioned first already after 30 m of the race. No sex differences were observed during any of the races for heart rate or blood lactate concentration.

    Conclusion: The average sex difference in sprint skiing performance was ∼12.5%, with varying differences for terrain-specific speeds. Moreover, females skied relatively slower uphill (at a lower gear) and thereby elicited more variation in their speed profiles compared to the males.

  • 3.
    Andersson, Erik
    et al.
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    McGawley, Kerry
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    A Comparison between Different Methods of Estimating Anaerobic Energy Production2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, no FEB, article id 82Article in journal (Refereed)
    Abstract [en]

    Purpose: The present study aimed to compare four methods of estimating anaerobic energy production during supramaximal exercise.

    Methods: Twenty-one junior cross-country skiers competing at a national and/or international level were tested on a treadmill during uphill (7°) diagonal-stride (DS) roller-skiing. After a 4-minute warm-up, a 4 × 4-min continuous submaximal protocol was performed followed by a 600-m time trial (TT). For the maximal accumulated O2 deficit (MAOD) method the V." role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; word-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; outline: 0px !important;">V.V.O2-speed regression relationship was used to estimate the V." role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; word-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; outline: 0px !important;">V.V.O2 demand during the TT, either including (4+Y, method 1) or excluding (4-Y, method 2) a fixed Y-intercept for baseline V." role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; word-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; outline: 0px !important;">V.V.O2. The gross efficiency (GE) method (method 3) involved calculating metabolic rate during the TT by dividing power output by submaximal GE, which was then converted to a V." role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; word-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; outline: 0px !important;">V.V.O2 demand. An alternative method based on submaximal energy cost (EC, method 4) was also used to estimate V." role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; word-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; outline: 0px !important;">V.V.O2 demand during the TT.

    Results: The GE/EC remained constant across the submaximal stages and the supramaximal TT was performed in 185 ± 24 s. The GE and EC methods produced identical V." role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; word-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; outline: 0px !important;">V.V.O2 demands and O2 deficits. The V." role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; word-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; outline: 0px !important;">V.V.O2 demand was ~3% lower for the 4+Y method compared with the 4-Y and GE/EC methods, with corresponding O2 deficits of 56 ± 10, 62 ± 10, and 63 ± 10 mL·kg−1, respectively (P < 0.05 for 4+Y vs. 4-Y and GE/EC). The mean differences between the estimated O2 deficits were −6 ± 5 mL·kg−1 (4+Y vs. 4-Y, P < 0.05), −7 ± 1 mL·kg−1 (4+Y vs. GE/EC, P < 0.05) and −1 ± 5 mL·kg−1 (4-Y vs. GE/EC), with respective typical errors of 5.3, 1.9, and 6.0%. The mean difference between the O2 deficit estimated with GE/EC based on the average of four submaximal stages compared with the last stage was 1 ± 2 mL·kg−1, with a typical error of 3.2%.

    Conclusions: These findings demonstrate a disagreement in the O2 deficits estimated using current methods. In addition, the findings suggest that a valid estimate of the O2 deficit may be possible using data from only one submaximal stage in combination with the GE/EC method.

  • 4.
    Biasetti, Jacopo
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Spazzini, Pier Giorgio
    Mechanics Division, National Institute of Metrological Research, Turin, Italy.
    Swedenborg, Jesper
    Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    An Integrated Fluid-Chemical Model Toward Modeling the Formation of Intra-Luminal Thrombus in Abdominal Aortic Aneurysms2012In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 3, no 266Article in journal (Refereed)
    Abstract [en]

    Abdominal Aortic Aneurysms (AAAs) are frequently characterized by the presence of an Intra-Luminal Thrombus (ILT) known to influence their evolution biochemically and biomechanically. The ILT progression mechanism is still unclear and little is known regarding the impact of the chemical species transported by blood flow on this mechanism. Chemical agonists and antagonists of platelets activation, aggregation, and adhesion and the proteins involved in the coagulation cascade (CC) may play an important role in ILT development. Starting from this assumption, the evolution of chemical species involved in the CC, their relation to coherent vortical structures (VSs) and their possible effect on ILT evolution have been studied. To this end a fluid-chemical model that simulates the CC through a series of convection-diffusion-reaction (CDR) equations has been developed. The model involves plasma-phase and surface-bound enzymes and zymogens, and includes both plasma-phase and membrane-phase reactions. Blood is modeled as a non-Newtonian incompressible fluid. VSs convect thrombin in the domain and lead to the high concentration observed in the distal portion of the AAA. This finding is in line with the clinical observations showing that the thickest ILT is usually seen in the distal AAA region. The proposed model, due to its ability to couple the fluid and chemical domains, provides an integrated mechanochemical picture that potentially could help unveil mechanisms of ILT formation and development.

  • 5.
    Bidkhori, Gholamreza
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Benfeitas, Rui
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Elmas, Ezgi
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kararoudi, Meisam Naeimi
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Arif, Muhammad
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nielsen, Jens
    Chalmers Univ Technol, Dept Biol & Biol Engn, Gothenburg, Sweden..
    Mardinoglu, Adil
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Metabolic Network-Based Identification and Prioritization o f Anticancer Targets Based on Expression Data in Hepatocellular Carcinoma2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 916Article in journal (Refereed)
    Abstract [en]

    Hepatocellular carcinoma (HCC) is a deadly form of liver cancer with high mortality worldwide. Unfortunately, the large heterogeneity of this disease makes it difficult to develop effective treatment strategies. Cellular network analyses have been employed to study heterogeneity in cancer, and to identify potential therapeutic targets. However, the existing approaches do not consider metabolic growth requirements, i.e., biological network functionality, to rank candidate targets while preventing toxicity to non-cancerous tissues. Here, we developed an algorithm to overcome these issues based on integration of gene expression data, genome-scale metabolic models, network controllability, and dispensability, as well as toxicity analysis. This method thus predicts and ranks potential anticancer non-toxic controlling metabolite and gene targets. Our algorithm encompasses both objective-driven and-independent tasks, and uses network topology to finally rank the predicted therapeutic targets. We employed this algorithm to the analysis of transcriptomic data for 50 HCC patients with both cancerous and non-cancerous samples. We identified several potential targets that would prevent cell growth, including 74 anticancer metabolites, and 3 gene targets (PRKACA, PGS1, and CRLS1). The predicted anticancer metabolites showed good agreement with existing FDA-approved cancer drugs, and the 3 genes were experimentally validated by performing experiments in HepG2 and Hep3B liver cancer cell lines. Our observations indicate that our novel approach successfully identifies therapeutic targets for effective treatment of cancer. This approach may also be applied to any cancer type that has tumor and non-tumor gene or protein expression data.

  • 6.
    Bjorklund, Glenn
    et al.
    Mid Sweden Univ, Dept Hlth Sci, Swedish Winter Sports Res Ctr, Ostersund, Sweden.;Swedish Sports Confederat, Stockholm, Sweden..
    Svarén, Mikael
    KTH, School of Engineering Sciences (SCI).
    Born, Dennis-Peter
    Swiss Fed Inst Sport, Dept Elite Sport, Magglingen, Switzerland..
    Stoeggl, Thomas
    Univ Salzburg, Dept Sport & Exercise Sci, Salzburg, Austria..
    Biomechanical Adaptations and Performance Indicators in Short Trail Running2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 506Article in journal (Refereed)
    Abstract [en]

    Our aims were to measure anthropometric and oxygen uptake ((V)over dot O-2) variables in the laboratory, to measure kinetic and stride characteristics during a trail running time trial, and then analyse the data for correlations with trail running performance. Runners (13 men, 4 women: mean age: 29 +/- 5 years; stature: 179.5 +/- 0.8 cm; body mass: 69.1 +/- 7.4 kg) performed laboratory tests to determine (V)over dot O-2 (max), running economy (RE), and anthropometric characteristics. On a separate day they performed an outdoor trail running time trial (two 3.5 km laps, total climb: 486 m) while we collected kinetic and time data. Comparing lap 2 with lap 1 (19:40 +/- 1:57 min vs. 21:08 +/- 2:09 min, P < 0.001), runners lost most time on the uphill sections and least on technical downhills (-2.5 +/- 9.1 s). Inter-individual performance varied most for the downhills (CV > 25%) and least on flat terrain (CV < 10%). Overall stride cycle and ground contact time (GCT) were shorter in downhill than uphill sections (0.64 +/- 0.03 vs. 0.84 +/- 0.09 s; 0.26 +/- 0.03 vs. 0.46 +/- 0.90 s, both P < 0.001). Force impulse was greatest on uphill (248 +/- 46 vs. 175 +/- 24 Ns, P < 0.001) and related to GCT (r = 0.904, P < 0.001). Peak force was greater during downhill than during uphill running (1106 +/- 135 vs. 959 +/- 104 N, P < 0.01). Performance was related to absolute and relative (V)over dot O-2 (max) (P < 0.01), vertical uphill treadmill speed (P < 0.001) and fat percent (P < 0.01). Running uphill involved the greatest impulse per step due to longer GCT while downhill running generated the highest peak forces. (V)over dot O-2 (max), vertical running speed and fat percent are important predictors for trail running performance. Performance between runners varied the most on downhills throughout the course, while pacing resembled a reversed J pattern. Future studies should focus on longer competition distances to verify these findings and with application of measures of 3D kinematics.

  • 7. Bjornson, Elias
    et al.
    Boren, Jan
    Mardinoglu, Adil
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. Chalmers University, Sweden.
    Personalized Cardiovascular Disease Prediction and Treatment-A Review of Existing Strategies and Novel Systems Medicine Tools2016In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 7, article id 2Article, review/survey (Refereed)
    Abstract [en]

    Cardiovascular disease (CVD) continues to constitute the leading cause of death globally. CVD risk stratification is an essential tool to sort through heterogeneous populations and identify individuals at risk of developing CVD. However, applications of current risk scores have recently been shown to result in considerable misclassification of high-risk subjects. In addition, despite long standing beneficial effects in secondary prevention, current CVD medications have in a primary prevention setting shown modest benefit in terms of increasing life expectancy. A systems biology approach to CVD risk stratification may be employed for improving risk-estimating algorithms through addition of high-throughput derived omics biomarkers. In addition, modeling of personalized benefit-of-treatment may help in guiding choice of intervention. In the area of medicine, realizing that CVD involves perturbations of large complex biological networks, future directions in drug development may involve moving away from a reductionist approach toward a system level approach. Here, we review current CVD risk scores and explore how novel algorithms could help to improve the identification of risk and maximize personalized treatment benefit. We also discuss possible future directions in the development of effective treatment strategies for CVD through the use of genome-scale metabolic models (GEMs) as well as other biological network-based approaches.

  • 8.
    Björklund, Glenn
    et al.
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. The Swedish Sports Confederation, Stockholm, Sweden.
    Swarén, Mikael
    Kungliga Tekniska Högskolan.
    Born, Dennis-Peter
    Swiss Federal Institute of Sport, Magglingen, Switzerland.
    Stöggl, Thomas
    University of Salzburg, Salzburg, Austria.
    Biomechanical Adaptations and Performance Indicators in Short Trail Running2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 506Article in journal (Refereed)
    Abstract [en]

    Our aims were to measure anthropometric and oxygen uptake (V&#x2D9;" role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; font-size: 20px; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; color: rgb(62, 61, 64); font-family: Georgia, "Times New Roman", Times, serif; position: relative; outline: 0px !important;">V˙V˙O2) variables in the laboratory, to measure kinetic and stride characteristics during a trail running time trial, and then analyse the data for correlations with trail running performance. Runners (13 men, 4 women: mean age: 29 ± 5 years; stature: 179.5 ± 0.8 cm; body mass: 69.1 ± 7.4 kg) performed laboratory tests to determine V&#x2D9;" role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; font-size: 20px; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; color: rgb(62, 61, 64); font-family: Georgia, "Times New Roman", Times, serif; position: relative; outline: 0px !important;">V˙V˙O2 max, running economy (RE), and anthropometric characteristics. On a separate day they performed an outdoor trail running time trial (two 3.5 km laps, total climb: 486 m) while we collected kinetic and time data. Comparing lap 2 with lap 1 (19:40 ± 1:57 min vs. 21:08 ± 2:09 min, P < 0.001), runners lost most time on the uphill sections and least on technical downhills (-2.5 ± 9.1 s). Inter-individual performance varied most for the downhills (CV > 25%) and least on flat terrain (CV < 10%). Overall stride cycle and ground contact time (GCT) were shorter in downhill than uphill sections (0.64 ± 0.03 vs. 0.84 ± 0.09 s; 0.26 ± 0.03 vs. 0.46 ± 0.90 s, both P < 0.001). Force impulse was greatest on uphill (248 ± 46 vs. 175 ± 24 Ns, P < 0.001) and related to GCT (r = 0.904, P< 0.001). Peak force was greater during downhill than during uphill running (1106 ± 135 vs. 959 ± 104 N, P< 0.01). Performance was related to absolute and relative V&#x2D9;" role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; font-size: 20px; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; color: rgb(62, 61, 64); font-family: Georgia, "Times New Roman", Times, serif; position: relative; outline: 0px !important;">V˙V˙O2 max (P < 0.01), vertical uphill treadmill speed (P < 0.001) and fat percent (P < 0.01). Running uphill involved the greatest impulse per step due to longer GCT while downhill running generated the highest peak forces. V&#x2D9;" role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; font-size: 20px; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; color: rgb(62, 61, 64); font-family: Georgia, "Times New Roman", Times, serif; position: relative; outline: 0px !important;">V˙V˙O2 max, vertical running speed and fat percent are important predictors for trail running performance. Performance between runners varied the most on downhills throughout the course, while pacing resembled a reversed J pattern. Future studies should focus on longer competition distances to verify these findings and with application of measures of 3D kinematics.

  • 9.
    Calbet, Jose A. L.
    et al.
    Univ Las Palmas Gran Canaria, Dept Phys Educ, Las Palmas Gran Canaria, Spain; IUIBS, Res Inst Biomed & Hlth Sci, Las Palmas Gran Canaria, Spain.
    Ponce-Gonzalez, Jesus G.
    Univ Las Palmas Gran Canaria, Dept Phys Educ, Las Palmas Gran Canaria, Spain.
    de la Calle-Herrero, Jaime
    Univ Las Palmas Gran Canaria, Dept Phys Educ, Las Palmas Gran Canaria, Spain.
    Perez-Suarez, Ismael
    Univ Las Palmas Gran Canaria, Dept Phys Educ, Las Palmas Gran Canaria, Spain; IUIBS, Res Inst Biomed & Hlth Sci, Las Palmas Gran Canaria, Spain..
    Martin-Rincon, Marcos
    Univ Las Palmas Gran Canaria, Dept Phys Educ, Las Palmas Gran Canaria, Spain; IUIBS, Res Inst Biomed & Hlth Sci, Las Palmas Gran Canaria, Spain.
    Santana, Alfredo
    Univ Las Palmas Gran Canaria, Dept Phys Educ, Las Palmas Gran Canaria, Spain; IUIBS, Res Inst Biomed & Hlth Sci, Las Palmas Gran Canaria, Spain.
    Morales-Alamo, David
    Univ Las Palmas Gran Canaria, Dept Phys Educ, Las Palmas Gran Canaria, Spain; IUIBS, Res Inst Biomed & Hlth Sci, Las Palmas Gran Canaria, Spain.
    Holmberg, Hans-Christer
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Exercise Preserves Lean Mass and Performance during Severe Energy Deficit: The Role of Exercise Volume and Dietary Protein Content2017In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 8, article id 483Article in journal (Refereed)
    Abstract [en]

    The loss of fat-free mass (FFM) caused by very-low-calorie diets (VLCD) can be attenuated by exercise. The aim of this study was to determine the role played by exercise and dietary protein content in preserving the lean mass and performance of exercised and non-exercised muscles, during a short period of extreme energy deficit (similar to 23 MJ deficit/day). Fifteen overweight men underwent three consecutive experimental phases: baseline assessment (PRE), followed by 4 days of caloric restriction and exercise (CRE) and then 3 days on a control diet combined with reduced exercise (CD). During CRE, the participants ingested a VLCD and performed 45 min of one-arm cranking followed by 8 h walking each day. The VLCD consisted of 0.8 g/kg body weight/day of either whey protein (PRO, n = 8) or sucrose (SU, n = 7). FFM was reduced after CRE (P < 0.001), with the legs and the exercised arm losing proportionally less FFM than the control arm [57% (P < 0.05) and 29% (P = 0.05), respectively]. Performance during leg pedaling, as reflected by the peak oxygen uptake and power output (Wpeak), was reduced after CRE by 15 and 12%, respectively (P < 0.05), and recovered only partially after CD. The deterioration of cycling performance was more pronounced in the whey protein than sucrose group (P < 0.05). Wpeak during arm cranking was unchanged in the control arm, but improved in the contralateral arm by arm cranking. There was a linear relationship between the reduction in whole-body FFM between PRE and CRE and the changes in the cortisol/free testosterone ratio (C/FT), serum isoleucine, leucine, tryptophan, valine, BCAA, and EAA (r = -0.54 to -0.71, respectively, P < 0.05). C/FT tended to be higher in the PRO than the SU group following CRE (P = 0.06). In conclusion, concomitant low-intensity exercise such as walking or arm cranking even during an extreme energy deficit results in remarkable preservation of lean mass. The intake of proteins alone may be associated with greater cortisol/free testosterone ratio and is not better than the ingestion of only carbohydrates for preserving FFM and muscle performance in interventions of short duration.

  • 10.
    Cardinale, Daniele A.
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Lännerström, Johan
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Manselin, Tom
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Södergård, Olof
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Mijwel, Sara
    Karolinska institutet, Sweden.
    Lindholm, P
    Karolinska institutet, Sweden.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Boushel, Robert
    University of British Columbia, Vancouver, BC, Canada..
    Influence of Hyperoxic-Supplemented High-Intensity Interval Training on Hemotological and Muscle Mitochondrial Adaptations in Trained Cyclists.2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 730Article in journal (Refereed)
    Abstract [en]

    Background: Hyperoxia (HYPER) increases O2 carrying capacity resulting in a higher O2 delivery to the working muscles during exercise. Several lines of evidence indicate that lactate metabolism, power output, and endurance are improved by HYPER compared to normoxia (NORM). Since HYPER enables a higher exercise power output compared to NORM and considering the O2 delivery limitation at exercise intensities near to maximum, we hypothesized that hyperoxic-supplemented high-intensity interval training (HIIT) would upregulate muscle mitochondrial oxidative capacity and enhance endurance cycling performance compared to training in normoxia. Methods: 23 trained cyclists, age 35.3 ± 6.4 years, body mass 75.2 ± 9.6 kg, height 179.8 ± 7.9 m, and VO2max 4.5 ± 0.7 L min-1 performed 6 weeks polarized and periodized endurance training on a cycle ergometer consisting of supervised HIIT sessions 3 days/week and additional low-intensity training 2 days/week. Participants were randomly assigned to either HYPER (FIO2 0.30; n = 12) or NORM (FIO2 0.21; n = 11) breathing condition during HIIT. Mitochondrial respiration in permeabilized fibers and isolated mitochondria together with maximal and submaximal VO2, hematological parameters, and self-paced endurance cycling performance were tested pre- and posttraining intervention. Results: Hyperoxic training led to a small, non-significant change in performance compared to normoxic training (HYPER 6.0 ± 3.7%, NORM 2.4 ± 5.0%; p = 0.073, ES = 0.32). This small, beneficial effect on the self-paced endurance cycling performance was not explained by the change in VO2max (HYPER 1.1 ± 3.8%, NORM 0.0 ± 3.7%; p = 0.55, ES = 0.08), blood volume and hemoglobin mass, mitochondrial oxidative phosphorylation capacity (permeabilized fibers: HYPER 27.3 ± 46.0%, NORM 16.5 ± 49.1%; p = 0.37, ES = 3.24 and in isolated mitochondria: HYPER 26.1 ± 80.1%, NORM 15.9 ± 73.3%; p = 0.66, ES = 0.51), or markers of mitochondrial content which were similar between groups post intervention. Conclusions: This study showed that 6 weeks hyperoxic-supplemented HIIT led to marginal gain in cycle performance in already trained cyclists without change in VO2max, blood volume, hemoglobin mass, mitochondrial oxidative phosphorylation capacity, or exercise efficiency. The underlying mechanisms for the potentially meaningful performance effects of hyperoxia training remain unexplained and may raise ethical questions for elite sport.

  • 11.
    Cardinale, Daniele A.
    et al.
    Swedish Sch Sport & Hlth Sci, Stockholm.
    Larsen, Filip J.
    Swedish Sch Sport & Hlth Sci, Stockholm.
    Schiffer, Tomas A.
    Karolinska Inst, Stockholm.
    Morales-Alamo, David
    Univ Las Palmas Gran Canaria, Las Palmas Gran Canaria, Spain; Res Inst Biomed & Hlth Sci IUIBS, Las Palmas De Gran Canad, Gran Canaria, Spain.
    Ekblom, Bjorn
    Swedish Sch Sport & Hlth Sci, Stockholm.
    Calbet, Jose A. L.
    Univ Las Palmas Gran Canaria, Las Palmas Gran Canaria, Spain; Res Inst Biomed & Hlth Sci IUIBS, Las Palmas De Gran Canad, Gran Canaria, Spain; Univ British Columbia, Vancouver, BC, Canada.
    Holmberg, Hans-Christer
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. Univ British Columbia, Vancouver, BC, Canada.
    Boushel, Robert
    Univ British Columbia, Vancouver, BC, Canada.
    Superior Intrinsic Mitochondria Respiration in Women Than in Men2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, no AUG, article id 1133Article in journal (Refereed)
    Abstract [en]

    Sexual dimorphism is apparent in humans, however, to date no studies have investigated mitochondria! function focusing on intrinsic mitochondrial respiration (i.e., mitochondrial respiration for a given amount of mitochondrial protein) and mitochondrial oxygen affinity (p50(mito)) in relation to biological sex in human. A skeletal muscle biopsy was donated by nine active women, and ten men matched for maximal oxygen consumption (VO2max) and by nine endurance trained men. Intrinsic mitochondrial respiration, assessed in isolated mitochondria, was higher in women compared to men when activating complex I (Cl-p) and complex I+II(Cl+IIp) (p < 0.05), and was similar to trained men (Cl-p, p = 0.053; Cl+IIp, p = 0.066). Proton leak and p50(mito) to were higher in women compared to men independent of VO2max. In conclusion, significant novel differences in mitochondrial oxidative function, intrinsic mitochondrial respiration and p50(mito) to exist between women and men. These findings may represent an adaptation in the oxygen cascade in women to optimize muscle oxygen uptake to compensate for a lower oxygen delivery during exercise.

  • 12.
    Cardinale, Daniele A.
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Schiffer, Tomas A
    Karolinska Institute.
    Morales-Alamo, David
    University of Las Palmas de Gran Canaria.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Calbet, Jose A L
    University of Las Palmas de Gran Canaria.
    Holmberg, Hans-Christer
    Mid Sweden University, Östersund, The University of British Columbia, Vancouver, BC, Canada..
    Boushel, Robert
    The University of British Columbia, Vancouver, BC, Canada..
    Superior Intrinsic Mitochondrial Respiration in Women Than in Men.2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 1133Article in journal (Refereed)
    Abstract [en]

    Sexual dimorphism is apparent in humans, however, to date no studies have investigated mitochondrial function focusing on intrinsic mitochondrial respiration (i.e., mitochondrial respiration for a given amount of mitochondrial protein) and mitochondrial oxygen affinity (p50mito) in relation to biological sex in human. A skeletal muscle biopsy was donated by nine active women, and ten men matched for maximal oxygen consumption (VO2max) and by nine endurance trained men. Intrinsic mitochondrial respiration, assessed in isolated mitochondria, was higher in women compared to men when activating complex I (CIP) and complex I+II (CI+IIP) (p < 0.05), and was similar to trained men (CIP, p = 0.053; CI+IIP, p = 0.066). Proton leak and p50mito were higher in women compared to men independent of VO2max. In conclusion, significant novel differences in mitochondrial oxidative function, intrinsic mitochondrial respiration and p50mito exist between women and men. These findings may represent an adaptation in the oxygen cascade in women to optimize muscle oxygen uptake to compensate for a lower oxygen delivery during exercise.

  • 13.
    Cardinale, Daniele A.
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll. Elite Performance Centre, Bosön.
    Lilja, Mats
    Karolinska institutet.
    Mandic, Mirko
    Karolinska institutet.
    Gustafsson, Thomas
    Karolinska institutet.
    Larsen, Filip J.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Lundberg, Tommy R.
    Karolinska institutet.
    Resistance Training with Co-ingestion of Anti-inflammatory Drugs Attenuates Mitochondrial Function2017In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 8, article id 1074Article in journal (Refereed)
    Abstract [en]

    Aim: The current study aimed to examine the effects of resistance exercise with concomitant consumption of high versus low daily doses of non-steroidal anti-inflammatory drugs (NSAIDs) on mitochondrial oxidative phosphorylation in skeletal muscle. As a secondary aim, we compared the effects of eccentric-overload with conventional training. Methods: Twenty participants were randomized to either a group taking high doses (3 x 400 mg/day) of ibuprofen (IBU; 27±5 yr; n=11) or a group ingesting a low dose (1 x 75 mg/day) of acetylsalicylic acid (ASA; 26±4 yr; n=9) during 8 weeks of supervised knee extensor resistance training. Each of the subject’s legs were randomized to complete the training program using either a flywheel (FW) device emphasizing eccentric-overload, or a traditional weight stack machine (WS). Maximal mitochondrial oxidative phosphorylation (CI+IIP) from permeabilized skeletal muscle bundles was assessed using high-resolution respirometry. Citrate synthase (CS) activity was assessed using spectrophotometric techniques and mitochondrial protein content using western blotting. Results: After training, CI+IIP decreased (P<0.05) in both IBU (23%) and ASA (29%) with no difference across medical treatments. Although CI+IIP decreased in both legs, the decrease was greater (interaction p = 0.015) in WS (33%, p = 0.001) compared with FW (19%, p = 0.078). CS activity increased (p = 0.027) with resistance training, with no interactions with medical treatment or training modality. Protein expression of ULK1 increased with training in both groups (p < 0.001). The increase in quadriceps muscle volume was not correlated with changes in CI+IIP (R=0.16). Conclusion: These results suggest that 8 weeks of resistance training with co-ingestion of anti-inflammatory drugs reduces mitochondrial function but increases mitochondrial content. The observed changes were not affected by higher doses of NSAIDs consumption, suggesting that the resistance training intervention was the prime mediator of the decreased mitochondrial phosphorylation. Finally, we noted that flywheel resistance training, emphasizing eccentric overload, rescued some of the reduction in mitochondrial function seen with conventional resistance training.

  • 14.
    Casas Garcia, Belén
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Viola, Frederica
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Cedersund, Gunnar
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Bolger, Ann F
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Univ Calif San Francisco, CA USA.
    Karlsson, Matts
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Non-invasive Assessment of Systolic and Diastolic Cardiac Function During Rest and Stress Conditions Using an Integrated Image-Modeling Approach2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 1515Article in journal (Refereed)
    Abstract [en]

    Background: The possibility of non-invasively assessing load-independent parameters characterizing cardiac function is of high clinical value. Typically, these parameters are assessed during resting conditions. However, for diagnostic purposes, the parameter behavior across a physiologically relevant range of heart rate and loads is more relevant than the isolated measurements performed at rest. This study sought to evaluate changes in non-invasive estimations of load-independent parameters of left-ventricular contraction and relaxation patterns at rest and during dobutamine stress. Methods: We applied a previously developed approach that combines non-invasive measurements with a physiologically-based, reduced-order model of the cardiovascular system to provide subject-specific estimates of parameters characterizing left ventricular function. In this model, the contractile state of the heart at each time point along the cardiac cycle is modeled using a time-varying elastance curve. Non-invasive data, including four-dimensional magnetic resonance imaging (4D Flow MRI) measurements, were acquired in nine subjects without a known heart disease at rest and during dobutamine stress. For each of the study subjects, we constructed two personalized models corresponding to the resting and the stress state. Results: Applying the modeling framework, we identified significant increases in the left ventricular contraction rate constant [from 1.5 +/- 0.3 to 2 +/- 0.5 (p = 0.038)] and relaxation constant [from 37.2 +/- 6.9 to 46.1 +/- 12 (p = 0.028)]. In addition, we found a significant decrease in the elastance diastolic time constant from 0.4 +/- 0.04 s to 0.3 +/- 0.03 s = 0.008). Conclusions: The integrated image-modeling approach allows the assessment of cardiovascular function given as model-based parameters. The agreement between the estimated parameter values and previously reported effects of dobutamine demonstrates the potential of the approach to assess advanced metrics of pathophysiology that are otherwise difficult to obtain non-invasively in clinical practice.

  • 15.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Skeletal Muscle Fiber Type in Hypoxia: Adaptation to High-Altitude Exposure and Under Conditions of Pathological Hypoxia2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 1450Article, review/survey (Refereed)
    Abstract [en]

    Skeletal muscle is able to modify its size, and its metabolic/contractile properties in response to a variety of stimuli, such as mechanical stress, neuronal activity, metabolic and hormonal influences, and environmental factors. A reduced oxygen availability, called hypoxia, has been proposed to inducemetabolic adaptations and loss ofmass in skeletal muscle. In addition, several evidences indicate that muscle fiber-type composition could be affected by hypoxia. The main purpose of this review is to explore the adaptation of skeletal muscle fiber-type composition to exposure to high altitude (ambient hypoxia) and under conditions of pathological hypoxia, including chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) and obstructive sleep apnea syndrome (OSAS). The muscle fiber-type composition of both adult animals and humans is not markedly altered during chronic exposure to high altitude. However, the fast-to-slow fiber-type transition observed in hind limb muscles during post-natal development is impaired in growing rats exposed to severe altitude. A slow-to-fast transition in fiber type is commonly found in lower limb muscles from patients with COPD and CHF, whereas a transition toward a slower fiber-type profile is often found in the diaphragm muscle in these two pathologies. A slow-to-fast transformation in fiber type is generally observed in the upper airway muscles in rodent models of OSAS. The factors potentially responsible for the adaptation of fiber type under these hypoxic conditions are also discussed in this review. The impaired locomotor activity most likely explains the changes in fiber type composition in growing rats exposed to severe altitude. Furthermore, chronic inactivity and muscle deconditioning could result in the slow-to-fast fiber-type conversion in lower limb muscles during COPD and CHF, while the factors responsible for the adaptation of muscle fiber type during OSAS remain hypothetical. Finally, the role played by cellular hypoxia, hypoxia-inducible factor-1 alpha (HIF-1 alpha), and other molecular regulators in the adaptation of muscle fiber-type composition is described in response to high altitude exposure and conditions of pathological hypoxia.

  • 16.
    Cibis, Merih
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Karlsson, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Left Atrial 4D Blood Flow Dynamics and Hemostasis following Electrical Cardioversion of Atrial Fibrillation2017In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 8, article id 1052Article in journal (Refereed)
    Abstract [en]

    Background: Electrical cardioversion in patients with atrial fibrillation is followed by a transiently impaired atrial mechanical function, termed atrial stunning. During atrial stunning, a retained risk of left atrial thrombus formation exists, which may be attributed to abnormal left atrial blood flow patterns. 4D Flow cardiovascular magnetic resonance (CMR) enables blood flow assessment from the entire three-dimensional atrial volume throughout the cardiac cycle. We sought to investigate left atrial 4D blood flow patterns and hemostasis during left atrial stunning and after left atrial mechanical function was restored. Methods: 4D Flow and morphological CMR data as well as blood samples were collected in fourteen patients at two time-points: 2-3 h (Time-1) and 4 weeks (Time-2) following cardioversion. The volume of blood stasis and duration of blood stasis were calculated. In addition, hemostasis markers were analyzed. Results: From Time-1 to Time-2: Heart rate decreased (61 +/- 7 vs. 56 +/- 8 bpm, p = 0.01); Maximum change in left atrial volume increased (8 +/- 4 vs. 22 +/- 15%, p = 0.009); The duration of stasis (68 +/- 11 vs. 57 +/- 8%, p = 0.002) and the volume of stasis (14 +/- 9 vs. 9 +/- 7%, p = 0.04) decreased; Thrombin-antithrombin complex (TAT) decreased (5.2 +/- 3.3 vs. 3.3 +/- 2.2it.g/L, p = 0.008). A significant correlation was found between TAT and the volume of stasis (r(2) = 0.69, p amp;lt; 0.001) at Time-1 and between TAT and the duration of stasis (r(2) = 0.34, p = 0.04) at Time-2. Conclusion: In this longitudinal study, left atrial multidimensional blood flow was altered and blood stasis was elevated during left atrial stunning compared to the restored left atrial mechanical function. The coagulability of blood was also elevated during atrial stunning. The association between blood stasis and hypercoagulability proposes that assessment of left atrial 4D flow can add to the pathophysiological understanding of thrombus formation during atrial fibrillation related atrial stunning.

  • 17.
    de Asis Fernandez, Fran
    et al.
    Departament of Health, Centro Superior de Estudios Universitarios La Salle, Universidad Autónoma de Madrid, Madrid, Spain; Department of Health Sciences, Mid Sweden University, Östersund, Sweden.
    Rodríguez-Zamora, Lara
    Örebro University, School of Health Sciences. Department of Health Sciences, Mid Sweden University, Östersund, Sweden.
    Schagatay, Erika
    Department of Health Sciences, Mid Sweden University, Östersund, Sweden.
    Hook Breathing Facilitates SaO(2) Recovery After Deep Dives in Freedivers With Slow Recovery2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 1076Article in journal (Refereed)
    Abstract [en]

    (SaO2)To facilitate recovery from hypoxia, many freedivers use a breathing method called "hook breathing" (HB) after diving, involving an interrupted exhale to build up intrapulmonary pressure. Some divers experience a delay in recovery of arterial oxygen saturation (SaO2) after diving, interpreted as symptoms of mild pulmonary edema, and facilitated recovery may be especially important in this group to avoid hypoxic "blackout." We examined the influence of HB on recovery of (SaO2) in freedivers with slow recovery (SR) and fast recovery (FR) of (SaO2) after deep "free immersion" (FIM) apnea dives to 30 m depth. Twenty-two male freedivers, with a mean (SD) personal best in the discipline FIM of 57(26) m, performed two 30 m deep dives, one followed by HB and one using normal breathing (NB) during recovery, at different days and weighted order. (SaO2) and heart rate (HR) were measured via pulse oximetry during recovery. The SR group (n = 5) had a faster (SaO2) recovery using HB, while the FR group (n = 17) showed no difference between breathing techniques. At 105 s, the SR group reached a mean (SD) SaO(2) of 95(5)% using HB, while using NB, their (SaO2) was 87(5)% (p < 0.05), and 105-120 s after surfacing(SaO2) was higher with HB (p < 0.05). In SR subjects, the average time needed to reach 95% (SaO2) with HB was 60 s, while it was 120 s at NB (p < 0.05). HR was similar in the SR group, while it was initially elevated at HB in the FR group (p < 0.05). We conclude that HB efficiently increases (SaO2) recovery in SR individuals, but not in the FR group. The proposed mechanism is that increased pulmonary pressure with HB will reverse any pulmonary edema and facilitate oxygen uptake in divers with delayed recovery.

  • 18. Debevec, T.
    et al.
    Ganse, B.
    Mittag, U.
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Mekjavic, I. B.
    Rittweger, J.
    Hypoxia aggravates inactivity-Related muscle wasting2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, no May, article id 494Article in journal (Refereed)
    Abstract [en]

    Poor musculoskeletal state is commonly observed in numerous clinical populations such as chronic obstructive pulmonary disease (COPD) and heart failure patients. It, however, remains unresolved whether systemic hypoxemia, typically associated with such clinical conditions, directly contributes to muscle deterioration. We aimed to experimentally elucidate the effects of systemic environmental hypoxia upon inactivity-related muscle wasting. For this purpose, fourteen healthy, male participants underwent three 21-day long interventions in a randomized, cross-over designed manner: (i) bed rest in normoxia (NBR; PiO2 = 133.1 ± 0.3 mmHg), (ii) bed rest in normobaric hypoxia (HBR; PiO2 = 90.0 ± 0.4 mmHg) and ambulatory confinement in normobaric hypoxia (HAmb; PiO2 = 90.0 ± 0.4 mmHg). Peripheral quantitative computed tomography and vastus lateralis muscle biopsies were performed before and after the interventions to obtain thigh and calf muscle cross-sectional areas and muscle fiber phenotype changes, respectively. A significant reduction of thigh muscle size following NBR (-6.9%, SE 0.8%; P &lt; 0.001) was further aggravated following HBR (-9.7%, SE 1.2%; P = 0.027). Bed rest-induced muscle wasting in the calf was, by contrast, not exacerbated by hypoxic conditions (P = 0.47). Reductions in both thigh (-2.7%, SE 1.1%, P = 0.017) and calf (-3.3%, SE 0.7%, P &lt; 0.001) muscle size were noted following HAmb. A significant and comparable increase in type 2× fiber percentage of the vastus lateralis muscle was noted following both bed rest interventions (NBR = +3.1%, SE 2.6%, HBR = +3.9%, SE 2.7%, P &lt; 0.05). Collectively, these data indicate that hypoxia can exacerbate inactivity-related muscle wasting in healthy active participants and moreover suggest that the combination of both, hypoxemia and lack of activity, as seen in COPD patients, might be particularly harmful for muscle tissue.

  • 19.
    Dillon-Murphy, Desmond
    et al.
    Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England..
    Marlevi, David
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging.
    Ruijsink, Bram
    Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England..
    Qureshi, Ahmed
    Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England..
    Chubb, Henry
    Stanford Univ, Dept Cardiothorac Surg, Palo Alto, CA 94304 USA..
    Kerfoot, Eric
    Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England..
    O'Neill, Mark
    Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England..
    Nordsleffen, David
    Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England..
    Aslanidi, Oleg
    Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England..
    de Vecchi, Adelaide
    Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England..
    Modeling Left Atrial Flow, Energy, Blood Heating Distribution in Response to Catheter Ablation Therapy2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 1757Article in journal (Refereed)
    Abstract [en]

    Introduction: Atrial fibrillation (AF) is a widespread cardiac arrhythmia that commonly affects the left atrium (LA), causing it to quiver instead of contracting effectively. This behavior is triggered by abnormal electrical impulses at a specific site in the atrial wall. Catheter ablation (CA) treatment consists of isolating this driver site by burning the surrounding tissue to restore sinus rhythm (SR). However, evidence suggests that CA can concur to the formation of blood clots by promoting coagulation near the heat source and in regions with low flow velocity and blood stagnation. Methods: A patient-specific modeling workflow was created and applied to simulate thermal-fluid dynamics in two patients pre- and post-CA. Each model was personalized based on pre- and post-CA imaging datasets. The wall motion and anatomy were derived from SSFP Cine MRI data, while the trans-valvular flow was based on Doppler ultrasound data. The temperature distribution in the blood was modeled using a modified Pennes bioheat equation implemented in a finite-element based Navier-Stokes solver. Blood particles were also classified based on their residence time in the LA using a particle-tracking algorithm. Results: SR simulations showed multiple short-lived vortices with an average blood velocity of 0.2-0.22 m/s. In contrast, AF patients presented a slower vortex and stagnant flow in the LA appendage, with the average blood velocity reduced to 0.08-0.14 m/s. Restoration of SR also increased the blood kinetic energy and the viscous dissipation due to the presence of multiple vortices. Particle tracking showed a dramatic decrease in the percentage of blood remaining in the LA for longer than one cycle after CA (65.9 vs. 43.3% in patient A and 62.2 vs. 54.8% in patient B). Maximum temperatures of 76 degrees and 58 degrees C were observed when CA was performed near the appendage and in a pulmonary vein, respectively. Conclusion: This computational study presents novel models to elucidate relations between catheter temperature, patient-specific atrial anatomy and blood velocity, and predict how they change from SR to AF. The models can quantify blood flow in critical regions, including residence times and temperature distribution for different catheter positions, providing a basis for quantifying stroke risks.

  • 20.
    Dueking, Peter
    et al.
    Univ Wurzburg, Inst Sport Sci, Dept Sports Sci, Integrat & Expt Training Sci, D-97070 Wurzburg, Germany.
    Hotho, Andreas
    Univ Wurzburg, Data Min & Informat Retrieval Grp, Comp Sci Artificial Intelligence & Appl Comp Sci, D-97070 Wurzburg, Germany.
    Holmberg, Hans-Christer
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. UiT Arctic Univ Norway, Sch Sport Sci, Tromso, Norway.
    Fuss, Franz Konstantin
    RMIT Univ, Sch Engn, Dept Mech & Automot Engn, Melbourne, Vic, Australia.
    Sperlich, Billy
    Univ Wurzburg, Inst Sport Sci, Dept Sports Sci, Integrat & Expt Training Sci, D-97070 Wurzburg, Germany.
    Comparison of Non-Invasive Individual Monitoring of the Training and Health of Athletes with Commercially Available Wearable Technologies2016In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 7, article id 71Article, review/survey (Refereed)
    Abstract [en]

    Athletes adapt their training daily to optimize performance, as well as avoid fatigue, overtraining and other undesirable effects on their health. To optimize training load, each athlete must take his/her own personal objective and subjective characteristics into consideration and an increasing number of wearable technologies (wearables) provide convenient monitoring of various parameters. Accordingly, it is important to help athletes decide which parameters are of primary interest and which wearables can monitor these parameters most effectively. Here, we discuss the wearable technologies available for non-invasive monitoring of various parameters concerning an athlete's training and health. On the basis of these considerations, we suggest directions for future development. Furthermore, we propose that a combination of several wearables is most effective for accessing all relevant parameters, disturbing the athlete as little as possible, and optimizing performance and promoting health.

  • 21.
    Düking, Peter
    et al.
    Julius Maximilians Univ, Wurzburg, Germany.
    Holmberg, Hans-Christer
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. Karolinska Inst; UiT Arctic Univ, Norway.
    Sperlich, Billy
    Julius Maximilians Univ, Wurzburg, Germany.
    Instant biofeedback provided by wearable sensor technology can help to optimize exercise and prevent injury and overuse2017In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 8, no APR, article id 167Article in journal (Refereed)
  • 22.
    Düking, Peter
    et al.
    University of Würzburg, Würzburg, Germany.
    Holmberg, Hans-Christer
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. UiT The Arctic University of Norway, Tromsø, Norway; University of British Columbia, Vancouver, BC, Canada.
    Sperlich, Billy
    University of Würzburg, Würzburg, Germany.
    The potential usefulness of virtual reality systems for athletes: A short SWOT analysis2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, no MAR, article id 128Article in journal (Refereed)
  • 23.
    Elinder, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Börjesson, Sara I.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels2017In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 8, article id 43Article, review/survey (Refereed)
    Abstract [en]

    Polyunsaturated fatty acids (PUFAs) act on most ion channels, thereby having significant physiological and pharmacological effects. In this review we summarize data from numerous PUFAs on voltage-gated ion channels containing one or several voltage-sensor domains, such as voltage-gated sodium (NaV), potassium (KV), calcium (CaV), and proton (HV) channels, as well as calcium-activated potassium (KCa), and transient receptor potential (TRP) channels. Some effects of fatty acids appear to be channel specific, whereas others seem to be more general. Common features for the fatty acids to act on the ion channels are at least two double bonds in cis geometry and a charged carboxyl group. In total we identify and label five different sites for the PUFAs. PUFA site 1: The intracellular cavity. Binding of PUFA reduces the current, sometimes as a time-dependent block, inducing an apparent inactivation. PUFA site 2: The extracellular entrance to the pore. Binding leads to a block of the channel. PUFA site 3: The intracellular gate. Binding to this site can bend the gate open and increase the current. PUFA site 4: The interface between the extracellular leaflet of the lipid bilayer and the voltage-sensor domain. Binding to this site leads to an opening of the channel via an electrostatic attraction between the negatively charged PUFA and the positively charged voltage sensor. PUFA site 5: The interface between the extracellular leaflet of the lipid bilayer and the pore domain. Binding to this site affects slow inactivation. This mapping of functional PUFA sites can form the basis for physiological and pharmacological modifications of voltage-gated ion channels.

  • 24.
    Elksnis, Andris
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Heterogeneity of Metabolic Defects in Type 2 Diabetes and Its Relation to Reactive Oxygen Species and Alterations in Beta-Cell Mass2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 107Article, review/survey (Refereed)
    Abstract [en]

    Type 2 diabetes (T2D) is a complex and heterogeneous disease which affects millions of people worldwide. The classification of diabetes is at an interesting turning point and there have been several recent reports on sub-classification of T2D based on phenotypical and metabolic characteristics. An important, and perhaps so far underestimated, factor in the pathophysiology of T2D is the role of oxidative stress and reactive oxygen species (ROS). There are multiple pathways for excessive ROS formation in T2D and in addition, beta-cells have an inherent deficit in the capacity to cope with oxidative stress. ROS formation could be causal, but also contribute to a large number of the metabolic defects in T2D, including beta-cell dysfunction and loss. Currently, our knowledge on beta-cell mass is limited to autopsy studies and based on comparisons with healthy controls. The combined evidence suggests that beta-cell mass is unaltered at onset of T2D but that it declines progressively. In order to better understand the pathophysiology of T2D, to identify and evaluate novel treatments, there is a need for in vivo techniques able to quantify beta-cell mass. Positron emission tomography holds great potential for this purpose and can in addition map metabolic defects, including ROS activity, in specific tissue compartments. In this review, we highlight the different phenotypical features of T2D and how metabolic defects impact oxidative stress and ROS formation. In addition, we review the literature on alterations of beta-cell mass in T2D and discuss potential techniques to assess beta-cell mass and metabolic defects in vivo.

  • 25.
    Fernández, Fran de Asís
    et al.
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. Universidad Autónoma de Madrid, Madrid, Spain.
    Rodríguez-Zamora, Lara
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. Örebro University, Örebro.
    Schagatay, Erika
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Hook Breathing Facilitates SaO2 Recovery After Deep Dives in Freedivers With Slow Recovery2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, p. 1-8, article id 1076Article in journal (Refereed)
    Abstract [en]

    To facilitate recovery from hypoxia, many freedivers use a breathing method called “hook breathing” (HB) after diving, involving an interrupted exhale to build up intrapulmonary pressure. Some divers experience a delay in recovery of arterial oxygen saturation (SaO2) after diving, interpreted as symptoms of mild pulmonary edema, and facilitated recovery may be especially important in this group to avoid hypoxic “blackout.” We examined the influence of HB on recovery of SaO2 in freedivers with slow recovery (SR) and fast recovery (FR) of SaO2 after deep “free immersion” (FIM) apnea dives to 30 m depth. Twenty-two male freedivers, with a mean (SD) personal best in the discipline FIM of 57(26) m, performed two 30 m deep dives, one followed by HB and one using normal breathing (NB) during recovery, at different days and weighted order. SaO2 and heart rate (HR) were measured via pulse oximetry during recovery. The SR group (n = 5) had a faster SaO2 recovery using HB, while the FR group (n = 17) showed no difference between breathing techniques. At 105 s, the SR group reached a mean (SD) SaO2 of 95(5)% using HB, while using NB, their SaO2 was 87(5)% (p < 0.05), and 105–120 s after surfacing SaO2 was higher with HB (p < 0.05). In SR subjects, the average time needed to reach 95% SaO2 with HB was 60 s, while it was 120 s at NB (p < 0.05). HR was similar in the SR group, while it was initially elevated at HB in the FR group (p < 0.05). We conclude that HB efficiently increases SaO2 recovery in SR individuals, but not in the FR group. The proposed mechanism is that increased pulmonary pressure with HB will reverse any pulmonary edema and facilitate oxygen uptake in divers with delayed recovery.

  • 26.
    Gennser, Mikael
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Blogg, S. L.
    SLB Consulting, Newbiggin On Lune, Cumbria, England..
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Mekjavic, Igor B.
    Jozef Stefan Inst, Dept Automat Biocybernet & Robot, Ljubljana, Slovenia.;Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC, Canada..
    Indices of Increased Decompression Stress Following Long-Term Bed Rest2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 442Article in journal (Refereed)
    Abstract [en]

    Human extravehicular activity (EVA) is essential to space exploration and involves risk of decompression sickness (DCS). On Earth, the effect of microgravity on physiological systems is simulated in an experimental model where subjects are confined to a 6 degrees head-down bed rest (HDBR). This model was used to investigate various resting and exercise regimen on the formation of venous gas emboli (VGE), an indicator of decompression stress, post-hyperbaric exposure. Eight healthy male subjects participating in a bed rest regimen also took part in this study, which incorporated five different hyperbaric exposure (HE) interventions made before, during and after the HDBR. Interventions i-iv were all made with the subjects lying in 6 degrees HD position. They included (C1) resting control, (C2) knee-bend exercise immediately prior to HE, (T1) HE during the fifth week of the 35-day HDBR period, (C3) supine cycling exercise during the HE. In intervention (C4), subjects remained upright and ambulatory. The HE protocol followed the Royal Navy Table 11 with 100 min spent at 18 m (280 kPa), with decompression stops at 6 m for 5 min, and at 3 m for 15 min. Post-HE, regular precordial Doppler audio measurements were made to evaluate any VGE produced post-dive. VGE were graded according to the Kisman Masurel scale. The number of bubbles produced was low in comparison to previous studies using this profile [Kisman integrated severity score (KISS) ranging from 0-1], and may be because subjects were young, and lay supine during both the HE and the 2 h measurement period post-HE for interventions i-iv. However, the HE during the end of HDBR produced significantly higher maximum bubble grades and KISS score than the supine control conditions (p < 0.01). In contrast to the protective effect of pre-dive exercise on bubble production, a prolonged period of bed rest prior to a HE appears to promote the formation of post-decompression VGE. This is in contrast to the absence of DCS observed during EVA. Whether this is due to a difference between hypo- and hyperbaric decompression stress, or that the HDBR model is a not a good model for decompression sensitivity during microgravity conditions will have to be elucidated in future studies.

  • 27. Ghaffari, Pouyan
    et al.
    Mardinoglu, Adil
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Chalmers University of Technology, Sweden.
    Nielsen, Jens
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Chalmers University of Technology, Sweden; Technical University of Denmark, Denmark.
    Cancer Metabolism: A Modeling Perspective2015In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 6, article id 382Article, review/survey (Refereed)
    Abstract [en]

    Tumor cells alter their metabolism to maintain unregulated cellular proliferation and survival, but this transformation leaves them reliant on constant supply of nutrients and energy. In addition to the widely studied dysregulated glucose metabolism to fuel tumor cell growth, accumulating evidences suggest that utilization of amino acids and lipids contributes significantly to cancer cell metabolism. Also recent progresses in our understanding of carcinogenesis have revealed that cancer is a complex disease and cannot be understood through simple investigation of genetic mutations of cancerous cells. Cancer cells present in complex tumor tissues communicate with the surrounding microenvironment and develop traits which promote their growth, survival, and metastasis. Decoding the full scope and targeting dysregulated metabolic pathways that support neoplastic transformations and their preservation requires both the advancement of experimental technologies for more comprehensive measurement of omics as well as the advancement of robust computational methods for accurate analysis of the generated data. Here, we review cancer-associated reprogramming of metabolism and highlight the capability of genome-scale metabolic modeling approaches in perceiving a system-level perspective of cancer metabolism and in detecting novel selective drug targets.

  • 28.
    Ghorbani, Ramin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Schmidt, Florian M.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Modeling pulmonary gas exchange and single-exhalation profiles of carbon monoxide2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 927Article in journal (Refereed)
    Abstract [en]

    Exhaled breath carbon monoxide (eCO) is a candidate biomarker for non-invasive assessment of oxidative stress and respiratory diseases. Standard end-tidal CO analysis, however, cannot distinguish, whether eCO reflects endogenous CO production, lung diffusion properties or exogenous sources, and is unable to resolve a potential airway contribution. Coupling real-time breath gas analysis to pulmonary gas exchange modeling holds promise to improve the diagnostic value of eCO. A trumpet model with axial diffusion (TMAD) is used to simulate the dynamics of CO gas exchange in the respiratory system and corresponding eCO concentrations for the first time. The mass balance equation is numerically solved employing a computationally inexpensive routine implementing the method of lines, which provides the distribution of CO in the respiratory tract during inhalation, breath-holding and exhalation with 1 mm spatial and 0.01 s temporal resolution. Initial estimates of the main TMAD parameters, the maximum CO fluxes and diffusing capacities in alveoli and airways, are obtained using healthy population tissue, blood and anatomical data. To verify the model, mouth-exhaled expirograms from two healthy subjects, measured with a novel, home-built laser-based CO sensor, are compared to single-exhalation profiles simulated using actual breath sampling data, such as exhalation flow rate (EFR) and volume. A very good agreement is obtained in exhalation phases I and III for EFRs between 55 and 220 ml/s and after 10 s and 20 s of breath-holding, yielding a unique set of TMAD parameters. The results confirm the recently observed EFR dependence of CO expirograms and suggest that measured end-tidal eCO is always lower than alveolar and capillary CO. Breath-holding allows the observation of close-to-alveolar CO concentrations and increases the sensitivity to the airway TMAD parameters in exhalation phase I. A parametric simulation study shows that a small increase in airway flux can be distinguished from an increase in alveolar flux, and that slight changes in alveolar flux and diffusing capacity have a significantly different effect on phase III of the eCO profiles.

  • 29.
    Gilgien, Matthias
    et al.
    Norwegian Sch Sport Sci, Oslo, Norway; Norwegian Ski Federat, Alpine Skiing, Oslo, Norway.
    Reid, Robert
    Norwegian Ski Federat, Alpine Skiing, Oslo, Norway.
    Raschner, Christian
    Univ Innsbruck, Olymp Training Ctr, Innsbruck, Austria.
    Supej, Matej
    Univ Ljubljana, Ljubljana, Slovenia.
    Holmberg, Hans-Christer
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. UiT Arctic Univ Norway, Tromsø, Norway; Univ British Columbia, Vancouver, BC, Canada.
    The Training of Olympic Alpine Ski Racers2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 1772Article in journal (Refereed)
    Abstract [en]

    Alpine combined was the only alpine ski racing event at the first Winter Olympic Games in 1936, but since then, slalom, giant slalom, super-G, downhill, and team events have also become Olympic events. Substantial improvements in slope preparation, design of courses, equipment, and the skills of Olympic alpine skiers have all helped this sport attain its present significance. Improved snow preparation has resulted in harder surfaces and improved equipment allows a more direct interaction between the skier and snow. At the same time, courses have become more challenging, with technical disciplines requiring more pronounced patterns of loading - unloading, with greater ground reaction forces. Athletes have adapted their training to meet these new demands, but little is presently known about these adaptations. Here, we describe how Olympic athletes from four of the major alpine ski racing nations prepared for the Olympic Games in South Korea in 2018. This overview describes their typical exercise programs with respect to physical conditioning, ski training and periodization, based on interviews with the coaching staff. Alpine ski racing requires mastery of a broad spectrum of physical, technical, mental, and social skills. We describe how athletes and teams deal with the multifactorial nature of the training required. Special emphasis is placed on sport-specific aspects, such as the combination of stimuli that interfere with training, training with chronic injury, training at altitude and in cold regions, the efficiency and effectiveness of ski training and testing, logistic challenges and their effects on fatigue, including the stress of frequent traveling. Our overall goal was to present as complete a picture of the training undertaken by Olympic alpine skiers as possible and on the basis of these findings propose how training for alpine ski racing might be improved.

  • 30.
    Ha, Hojin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Kangwon Natl Univ, South Korea.
    Ziegler, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Welander, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Bjarnegård, Niclas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lindenberger, Marcus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Age-Related Vascular Changes Affect Turbulence in Aortic Blood Flow2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 36Article in journal (Refereed)
    Abstract [en]

    Turbulent blood flow is implicated in the pathogenesis of several aortic diseases but the extent and degree of turbulent blood flow in the normal aorta is unknown. We aimed to quantify the extent and degree of turbulece in the normal aorta and to assess whether age impacts the degree of turbulence. 22 young normal males (23.7 +/- 3.0 y.o.) and 20 old normal males (70.9 +/- 3.5 y.o.) were examined using four dimensional flow magnetic resonance imaging (4D Flow MRI) to quantify the turbulent kinetic energy (TKE), a measure of the intensity of turbulence, in the aorta. All healthy subjects developed turbulent flow in the aorta, with total TKE of 3-19 mJ. The overall degree of turbulence in the entire aorta was similar between the groups, although the old subjects had about 73% more total TKE in the ascending aorta compared to the young subjects (young = 3.7 +/- 1.8 mJ, old = 6.4 +/- 2.4 mJ, p amp;lt; 0.001). This increase in ascending aorta TKE in old subjects was associated with age-related dilation of the ascending aorta which increases the volume available for turbulence development. Conversely, age-related dilation of the descending and abdominal aorta decreased the average flow velocity and suppressed the development of turbulence. In conclusion, turbulent blood flow develops in the aorta of normal subjects and is impacted by age-related geometric changes. Non-invasive assessment enables the determination of normal levels of turbulent flow in the aorta which is a prerequisite for understanding the role of turbulence in the pathophysiology of cardiovascular disease.

  • 31.
    Hedlund, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Lindelöf, Nina
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Danish Research Center for Magnetic Resonance, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.
    Rosendahl, Erik
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Development and Feasibility of a Regulated, Supramaximal High-Intensity Training Program Adapted for Older Individuals2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 590Article in journal (Refereed)
    Abstract [en]

    Background: High-intensity training (HIT) with extremely short intervals (designated here as supramaximal HIT) is a time-efficient training method for health and performance. However, a protocol for regulation and control of intensity is missing, impeding implementation in various groups, such as older individuals.

    Methods: This study presents the development and characteristics of a novel training protocol with regulated and controlled supramaximal intervals adapted for older people. Using both quantitative and qualitative analyses, we explored the feasibility of the program, performed in a group training setting, with physically active older individuals (aged 65–75, n = 7; five women). The developed supramaximal HIT program consisted of 10 × 6 s cycle sprint intervals with ∼1 min of active recovery with the following key characteristics: (1) an individual target power output was reached and maintained during all intervals and regulated and expressed as the percentage of the estimated maximum mean power output for the duration of the interval (i.e., 6 s); (2) pedaling cadence was standardized for all participants, while resistance was individualized; and (3) the protocol enabled controlled and systematic adjustments of training intensity following standardized escalation criteria.

    Aim: Our aim was to test the feasibility of a novel training regimen with regulated and controlled supramaximal HIT, adapted for older people. The feasibility criteria for the program were to support participants in reaching a supramaximal intensity (i.e., power output > 100% of estimated VO2 max), avoid inducing a negative affective response, and have participants perceive it as feasible and acceptable.

    Results: All feasibility criteria were met. The standardized escalation procedure provided safe escalation of training load up to a supramaximal intensity (around three times the power output at estimated VO2 max). The participants never reported negative affective responses, and they perceived the program as fun and feasible.

    Conclusion: This novel program offers a usable methodology for further studies on supramaximal HIT among older individuals with different levels of physical capacity. Future research should explore the effects of the program in various populations of older people and their experiences and long-term adherence compared with other forms of training.

  • 32.
    Holmström, Pontus
    et al.
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Mulder, Eric
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Lodin-Sundström, Angelica
    Mid Sweden University, Faculty of Human Sciences, Department of Nursing Sciences.
    Limbu, Prakash
    Nepalese Army Inst Hlth Sci, Kathmandu, Nepal.
    Schagatay, Erika
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    The Magnitude of Diving Bradycardia During Apnea at Low-Altitude Reveals Tolerance to High Altitude Hypoxia2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, p. 1-12, article id 1075Article in journal (Refereed)
    Abstract [en]

    Acute mountain sickness (AMS) is a potentially life-threatening illness that may develop during exposure to hypoxia at high altitude (HA). Susceptibility to AMS is highly individual, and the ability to predict it is limited. Apneic diving also induces hypoxia, and we aimed to investigate whether protective physiological responses, i.e., the cardiovascular diving response and spleen contraction, induced during apnea at low-altitude could predict individual susceptibility to AMS. Eighteen participants (eight females) performed three static apneas in air, the first at a fixed limit of 60 s (A1) and two of maximal duration (A2-A3), spaced by 2 min, while SaO(2), heart rate (HR) and spleen volume were measured continuously. Tests were conducted in Kathmandu (1470 m) before a 14 day trek to mount Everest Base Camp (5360 m). During the trek, participants reported AMS symptoms daily using the Lake Louise Questionnaire (LLQ). The apnea-induced HR-reduction (diving bradycardia) was negatively correlated with the accumulated LLQ score in A1 (r(s) = -0.628, p= 0.005) and A3 (r(s) = -0.488, p = 0.040) and positively correlated with SaO(2) at 4410 m (A1: r = 0.655, p = 0.003; A2: r = 0.471, p = 0.049; A3: r = 0.635, p = 0.005). Baseline spleen volume correlated negatively with LLQ score (r(s) = -0.479, p = 0.044), but no correlation was found between apnea-induced spleen volume reduction with LLQ score (r(s) = 0.350, p = 0.155). The association between the diving bradycardia and spleen size with AMS symptoms suggests links between physiological responses to HA and apnea. Measuring individual responses to apnea at sea-level could provide means to predict AMS susceptibility prior to ascent.

  • 33.
    Ihalainen, Johanna K.
    et al.
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. Univ Jyväskylä, Jyväskylä, Finland.
    Inglis, Alistair
    Univ Jyväskylä, Jyväskylä, Finland.
    Mäkinen, Tuomas
    LIKES Res Ctr Sport & Hlth Sci, Jyväskylä, Finland.
    Newton, Robert U.
    Edith Cowan Univ, Joondalup, WA, Australia.
    Kainulainen, Heikki
    Univ Jyväskylä, Jyväskylä, Finland.
    Kyröläinen, Heikki
    Univ Jyväskylä, Jyväskylä, Finland.
    Walker, Simon
    Univ Jyväskylä, Jyväskylä, Finland.
    Strength Training Improves Metabolic Health Markers in Older Individual Regardless of Training Frequency2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, no FEB, article id 32Article in journal (Refereed)
    Abstract [en]

    The main purpose of the present study was to investigate the effect of frequency, thereby increasing training volume, of resistance training on body composition, inflammation markers, lipid and glycemic profile in healthy older individuals (age range 65-75 year). Ninety-two healthy participants were randomly assigned to one of four groups; performing strength training one- (EX1), two- (EX2), or three- (EX3) times-per-week and a non-training control (CON) group. Whole-body strength training was performed using 2-5 sets and 4-12 repetitions per exercise and 7-9 exercises per session. All training groups attended supervised resistance training for 6 months. Body composition was measured by dual X-ray absorptiometry and fasting blood samples were taken pre- and post-training. There were significant main effects of time for total fat mass (F = 28.12, P < 0.001) and abdominal fat mass (F = 20.72, P < 0.001). Pre- to post-study, statistically significant reductions in fat mass (Delta = -1.3 +/- 1.4 kg, P < 0.001, n = 26) were observed in EX3. Pre- to post-study reductions in low density lipoprotein (LDL) concentration (Delta = -0.38 +/- 0.44 mmol.L-1 , P = 0.003, n = 19) were observed only in EX3, whereas a significant pre- to post-study increases in high density lipoprotein (HDL) concentration (0.14-0.19 mmol.L-1) were observed in all training groups. Most variables at baseline demonstrated a significant (negative) relationship when correlating baseline values with their change during the study including: Interleukin-6 (IL-6) (r = -0.583, P < 0.001), high-sensitivity c-reactive protein (hs-CRP) (r = -0.471, P < 0.001, and systolic blood pressure (r = -0.402, P = 0.003). The present study suggests that having more than two resistance training sessions in a week could be of benefit in the management of body composition and lipid profile. Nevertheless, interestingly, and importantly, those individuals with a higher baseline in systolic blood pressure, IL-6 and hs-CRP derived greatest benefit from the resistance training intervention, regardless of how many times-a-week they trained. Finally, the present study found no evidence that higher training frequency would induce greater benefit regarding inflammation markers or glycemic profile in healthy older adults.

  • 34.
    Jauhiainen, Suvi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Univ Eastern Finland, AI Virtanen Inst Mol Sci, Kuopio, Finland.
    Laakkonen, Johanna P.
    Univ Eastern Finland, AI Virtanen Inst Mol Sci, Kuopio, Finland.
    Ketola, Kirsi
    Univ Eastern Finland, Inst Biomed, Kuopio, Finland.
    Toivanen, Pyry, I
    Univ Eastern Finland, AI Virtanen Inst Mol Sci, Kuopio, Finland.
    Nieminen, Tina
    Univ Eastern Finland, AI Virtanen Inst Mol Sci, Kuopio, Finland.
    Ninchoji, Takeshi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Levonen, Anna-Liisa
    Univ Eastern Finland, AI Virtanen Inst Mol Sci, Kuopio, Finland.
    Kaikkonen, Minna U.
    Univ Eastern Finland, AI Virtanen Inst Mol Sci, Kuopio, Finland.
    Ylä-Herttuala, Seppo
    Univ Eastern Finland, AI Virtanen Inst Mol Sci, Kuopio, Finland;Kuopio Univ Hosp, Heart Ctr & Gene Therapy Unit, Kuopio, Finland.
    Axon Guidance-Related Factor FLRT3 Regulates VEGF-Signaling and Endothelial Cell Function2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 224Article in journal (Refereed)
    Abstract [en]

    Vascular endothelial growth factors (VEGFs) are key mediators of endothelial cell (EC) function in angiogenesis. Emerging knowledge also supports the involvement of axon guidance-related factors in the regulation of angiogenesis and vascular patterning. In the current study, we demonstrate that fibronectin and leucine-rich transmembrane protein-3 (FLRT3), an axon guidance-related factor connected to the regulation of neuronal cell outgrowth and morphogenesis but not to VEGF-signaling, was upregulated in ECs after VEGF binding to VEGFR2. We found that FLRT3 exhibited a transcriptionally paused phenotype in non-stimulated human umbilical vein ECs. After VEGF-stimulation its nascent RNA and mRNA-levels were rapidly upregulated suggesting that the regulation of FLRT3 expression is mainly occurring at the level of transcriptional elongation. Blockage of FLRT3 by siRNA decreased survival of ECs and their arrangement into capillary-like structures but enhanced cell migration and wound closure in wound healing assay. Bifunctional role of FLRT3 in repulsive vs. adhesive cell signaling has been already detected during embryogenesis and neuronal growth, and depends on its interactions either with UNC5B or another FLRT3 expressed by adjacent cells. In conclusion, our findings demonstrate that besides regulating neuronal cell outgrowth and morphogenesis, FLRT3 has a novel role in ECs via regulating VEGF-stimulated EC-survival, migration, and tube formation. Thus, FLRT3 becomes a new member of the axon guidance-related factors which participate in the VEGF-signaling and regulation of the EC functions.

  • 35. Jeruszka-Bielak, Marta
    et al.
    Kollajtis-Dolowy, Anna
    Santoro, Aurelia
    Ostan, Rita
    Berendsen, Agnes A. M.
    Jennings, Amy
    Meunier, Nathalie
    Marseglia, Anna
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Caumon, Elodie
    Gillings, Rachel
    de Groot, Lisette C. P. G. M.
    Franceschi, Claudio
    Hieke, Sophie
    Pietruszka, Barbara
    Are Nutrition-Related Knowledge and Attitudes Reflected in Lifestyle and Health Among Elderly People? A Study Across Five European Countries2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 994Article in journal (Refereed)
    Abstract [en]

    Background: Nutrition-related knowledge (NRK) and nutrition-related attitudes (NRAs) are necessary for dietary changes toward healthier dietary patterns. In turn, healthier dietary patterns can be beneficial in maintaining health of older adults. Therefore, the aim of this cross-sectional study was to investigate whether NRK and NRAs were associated with lifestyle and health features among older adults (65+ years) from five European countries (France, Italy, Poland, the Netherlands and United Kingdom). Methods: Within the European project NU-AGE, 1,144 healthy elderly volunteers (65-79 years) were randomly assigned to two groups: intervention (NU-AGE diet) or control. After 1-year of follow-up, both NRK and NRAs were assessed during exit interviews, in combination with a number of lifestyle and health variables (e.g., physical activity, smoking, alcohol use, BMI, self-assessed health status). Multivariable linear regression models were used in data analysis. Results: In the NU-AGE study sample, good NRK was associated with lower BMI and higher physical activity. More positive NRAs were related to lower BMI and self-reported very good or good appetite. Moreover, both NRK and NRAs were associated with some socio-economic determinants, like financial situation, age, education, living area (for NRK), and country (for NRAs). Participants in the intervention group showed a better NRK (beta = 0 367 [95% CI 0.117; 0.617], p = 0.004) and more positive NRAs beta = 0.838 [95% CI 0.318, 1.358], p = 0.002) than those in the control group. Higher self-evaluated knowledge was also significantly related to more positive NRAs (p < 0.001). The most popular sources of nutrition information were food labels, books and magazines on health, the dietitian and the doctor's office, although their importance varied significantly among countries, and, to a lesser extent, between women and men and between intervention and control group. Conclusion: Higher NRK and NRA scores were associated with lower BMI and higher physical activity level. Therefore, a good nutrition-related knowledge and positive nutrition-related attitudes can strongly and positively influence the health status and quality of life among the older population. These results offer a great opportunity for policy makers to implement educational programs in order to counteract the epidemic of obesity and to improve the health span of European population.

  • 36.
    Karlsson, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Erixon, Hanna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bolger, Ann
    Univ Calif San Francisco, CA USA.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Post-cardioversion Improvement in LV Function Defined by 4D Flow Patterns and Energetics in Patients With Atrial Fibrillation2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 659Article in journal (Refereed)
    Abstract [en]

    Background: Atrial fibrillation (AF) is a prevalent cause of cardiovascular morbidity, including thromboembolism and heart failure. Left ventricular dysfunction (LVD) detected in AF patients may be either precursor or consequence of the arrythmia. Successful cardioversion of chronic AF is often followed by a transient period of left atrial (LA) stunning, where depressed mechanical atrial contraction persists despite reinstitution of sinus rhythm. To determine if AF-associated LVD would improve with resolution of LA dysfunction, AF patients were examined immediately and 4 weeks after cardioversion to sinus rhythm. 4D flow cardiovascular magnetic resonance (CMR) assesses ventricular function according to the volumes and energetics of functional components of the LV volume. Previously, described 4D CMR markers of LVD include decreased volume and end-diastolic kinetic energy (KE) of the Direct flow, which is the portion of LV volume that passes directly from inflow to outflow in a single cycle. We hypothesize that impaired LV flow patterns and energetics will be found immediately after cardioversion during atrial stunning, and that those parameters will improve as atrial function returns. Methods: Ten patients with a history of AF underwent CMR 2-3 h (Time-1) and 4 weeks (time-2), following electrical cardioversion to sinus rhythm. 4D phase-contrast velocity data and morphological images were acquired at a 3T CMR system. Using a previously evaluated method, pathlines were emitted from the LV end diastolic volume (LVEDV) and traced forward and backward in time until end-systole. The LVEDV was automatically separated into four functional flow components whose volume and KE were calculated. Results: Left atrial fractional area change increased over the follow-up period (P = 0.001), indicating recovery of LA mechanical function. LVEF increased between Time-1 and Time-2 (P = 0.003); LVEDVI did not change (P = 0.319). Over that interval, the ratios of Direct flow/LVEDV volume and KE increased (P = 0.001 and P = 0.003, respectively), while the ratios of Residual volume/LVEDV volume and KE decreased (P = 0.001 and P = 0.005, respectively). Conclusion: Post-cardioversion recovery of LA function was associated with improvements in conventional and 4D CMR markers of LV function. Flow-specific measures demonstrate the negative but potentially reversible impact of LA dysfunction on volume and energetic aspects of LV function.

  • 37.
    Karlsson, Øyvind
    et al.
    Department of Physical Performance, Norwegian School of Sport Sciences.
    Gilgien, Matthias
    Department of Physical Performance, Norwegian School of Sport Sciences.
    Nøstdahl Gløersen, Øyvind
    Department of Physical Performance, Norwegian School of Sport Sciences.
    Rud, Bjarne
    Department of Physical Performance, Norwegian School of Sport Sciences.
    Losnegard, Thomas
    Department of Physical Performance, Norwegian School of Sport Sciences.
    Exercise Intensity During Cross-Country Skiing Described by Oxygen Demands in Flat and Uphill Terrain2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 846Article in journal (Refereed)
    Abstract [en]

    Purpose: In this study wearable global navigation satellite system units were used on athletes to investigate pacing patterns by describing exercise intensities in flat and uphill terrain during a simulated cross-country ski race.

    Methods: Eight well-trained male skiers (age: 23.0 ± 4.8 years, height: 183.8 ± 6.8 cm, weight: 77.1 ± 6.1 kg, VO2peak: 73 ± 5 mL⋅kg-1⋅min-1) completed a 13.5-km individual time trial outdoors and a standardized indoor treadmill protocol on roller skis. Positional data were recorded during the time trial using a differential global navigation satellite system to calculate external workloads in flat and uphill terrain. From treadmill tests, the individual relationships between oxygen consumption and external workload in flat (1°) and uphill (8°) terrain were determined, in addition to VO2peak and the maximal accumulated O2-deficit. To estimate the exercise intensity in the time trial, the O2-demand in two different flat and five different uphill sections was calculated by extrapolation of individual O2-consumption/workload ratios.

    Results: There was a significant interaction between section and average O2-demands, with higher O2-demands in the uphill sections (110–160% of VO2peak) than in the flat sections (≤100% of VO2peak) (p < 0.01). The maximal accumulated O2-deficit associated with uphill treadmill roller skiing was significantly higher compared to flat (6.2 ± 0.5 vs. 4.6 ± 0.5 L, p < 0.01), while no significant difference was found in VO2peak.

    Conclusion: Cross-country (XC) skiers repeatedly applied exercise intensities exceeding their maximal aerobic power. ΣO2-deficits were higher during uphill skiing compared to flat which has implications for the duration and magnitude of supramaximal work rates that can be applied in different types of terrain.

  • 38.
    Konz, Tobias
    et al.
    Nestlé Research, Vers-Chez-Les-Blanc, Lausanne, Switzerland.
    Santoro, Aurelia
    Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy; C.I.G. Interdepartmental Centre “L. Galvani”, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
    Goulet, Laurence
    Nestlé Research, Vers-Chez-Les-Blanc, Lausanne, Switzerland.
    Bazzocchi, Alberto
    Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
    Battista, Giuseppe
    Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
    Nicoletti, Claudio
    Department of Experimental and Clinical Medicine, Section of Anatomy, University of Florence, Florence, Italy; Gut Health Institute Strategic Programme, Quadram Institute Bioscience, Norwich, United Kingdom.
    Kadi, Fawzi
    Örebro University, School of Health Sciences.
    Ostan, Rita
    Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy; C.I.G. Interdepartmental Centre “L. Galvani”, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
    Goy, Michael
    Nestlé Research, EPFL Innovation Park, Lausanne, Switzerland.
    Monnard, Caroline
    Nestlé Research, Vers-Chez-Les-Blanc, Lausanne, Switzerland.
    Martin, Francois-Pierre
    Nestlé Research, EPFL Innovation Park, Lausanne, Switzerland.
    Feige, Jerome N.
    Nestlé Research, EPFL Innovation Park, Lausanne, Switzerland.
    Franceschi, Claudio
    Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy; Institute of Neurological Sciences (IRCCS), Bologna, Italy.
    Rezzi, Serge
    Nestlé Research, Vers-Chez-Les-Blanc, Lausanne, Switzerland.
    Sex-Specific Associations of Blood-Based Nutrient Profiling With Body Composition in the Elderly2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 1935Article in journal (Refereed)
    Abstract [en]

    The intake of adequate amounts and types of nutrients is key for sustaining health and a good quality of life, particularly in the elderly population. There is considerable evidence suggesting that physiological changes related to age and sex modify nutritional needs, and this may be related to age-associated changes in body composition (BC), specifically in lean and fat body mass. However, there is a clear lack of understanding about the association of nutrients in blood and BC parameters in the elderly. This study investigated the relationships among blood nutrients (amino acids, fatty acids, major elements, trace-elements, and vitamins), BC and nutrient intake in a population of 176 healthy male and female Italian adults between the ages of 65 and 79 years. 89 blood markers, 77 BC parameters and dietary intake were evaluated. Multivariate data analysis was applied to infer relationships between datasets. As expected, the major variability between BC and the blood nutrient profile (BNP) observed was related to sex. Aside from clear sex-specific differences in BC, female subjects had higher BNP levels of copper, copper-to-zinc ratio, phosphorous and holotranscobalamin II and lower concentrations of branched-chain amino acids (BCAAs) and proline. Fat mass, percentage of fat mass, percentage of lean mass and the skeletal muscle index (SMI) correlated the most with BNP in both sexes. Our data showed positive correlations in male subjects among ethanolamine, glycine, albumin, and sulfur with SMI, while palmitoleic acid and oleic acid exhibited negative correlations. This differed in female subjects, where SMI was positively associated with albumin, folic acid and sulfur, while CRP, proline and cis-8,11,14-eicosatrienoic acid were negatively correlated. We investigated the influence of diet on the observed BNP and BC correlations. Intriguingly, most of the components of the BNP, except for folate, did not exhibit a correlation with nutrient intake data. An understanding of the physiological and biochemical processes underpinning the observed sex-specific correlations between BNP and BC could help in identifying nutritional strategies to manage BC-changes in aging. This would contribute to a deeper understanding of aging-associated nutritional needs with the aim of helping the elderly population to maintain metabolic health.

  • 39.
    Kubrak, Olga I.
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Kucerova, Lucie
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Theopold, Ulrich
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Nylin, Sören
    Stockholm University, Faculty of Science, Department of Zoology.
    Nässel, Dick R.
    Stockholm University, Faculty of Science, Department of Zoology.
    Characterization of Reproductive Dormancy in Male Drosophila melanogaster2016In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 7, article id 572Article in journal (Refereed)
    Abstract [en]

    Insects are known to respond to seasonal and adverse environmental changes by entering dormancy, also known as diapause. In some insect species, including Drosophila melanogaster, dormancy occurs in the adult organism and postpones reproduction. This adult dormancy has been studied in female flies where it is characterized by arrested development of ovaries, altered nutrient stores, lowered metabolism, increased stress and immune resistance and drastically extended lifespan. Male dormancy, however, has not been investigated in D. melanogaster, and its physiology is poorly known in most insects. Here we show that unmated 3-6 h old male flies placed at low temperature (11 degrees C) and short photoperiod (10 Light:14 Dark) enter a state of dormancy with arrested spermatogenesis and development of testes and male accessory glands. Over 3 weeks of diapause we see a dynamic increase in stored carbohydrates and an initial increase and then a decrease in lipids. We also note an up-regulated expression of genes involved in metabolism, stress responses and innate immunity. Interestingly, we found that male flies that entered reproductive dormancy do not attempt to mate females kept under non-diapause conditions (25 degrees C, 1 2L:1 2D), and conversely non-diapausing males do not mate females in dormancy. In summary, our study shows that male D. melanogaster can enter reproductive dormancy. However, our data suggest that dormant male flies deplete stored nutrients faster than females, studied earlier, and that males take longer to recover reproductive capacity after reintroduction to non-diapause conditions.

  • 40.
    Laaksonen, Marko
    et al.
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Jonsson, Malin
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Holmberg, Hans-Christer
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. UiT The Arctic University of Norway, Tromsø, Norway; The University of British Columbia, Vancouver, BC, Canada.
    The Olympic biathlon – Recent advances and perspectives after Pyeongchang2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, no JUL, article id 796Article in journal (Refereed)
    Abstract [en]

    The biathlon, combining cross-country ski skating with rifle marksmanship, has been an Olympic event since the Winter Games in Squaw Valley, United States, in 1960. As a consequence of replacing the classical with the skating technique in the 1980s, as well as considerable improvements in equipment and preparation of ski tracks and more effective training, the average biathlon skiing speed has increased substantially. Moreover, the mass-start, pursuit, and sprint races have been introduced. Indeed, two of the four current individual Olympic biathlon competitions involve mass-starts, where tactics play a major role and the outcome is often decided during the last round of shooting or final sprint. Biathlon is a demanding endurance sport requiring extensive aerobic capacity. The wide range of speeds and slopes involved requires biathletes to alternate continuously between and adapt different skating sub-techniques duringraces, a technical complexity that places a premium on efficiency. Although the relative amounts of endurance training at different levels of intensity have remained essentially constant during recent decades, today’s biathletes perform more specific endurance training on roller skis on terrain similar to that used for competition, with more focus on the upper-body, systematic strength and power training and skiing at higher speeds. Success in the biathlon also requires accurate and rapid shooting while simultaneously recovering from high-intensity skiing. Many different factors, including body sway, triggering behavior, and even psychology, influence the shooting performance. Thus, the complexity of biathlon deserves a greater research focus on areas such as race tactics, skating techniques, or shooting process.

  • 41.
    Laaksonen, Marko
    et al.
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Kyröläinen, Heikki
    University of Jyväskylä, Finland.
    Kemppainen, Jukka
    University of Turku, Finland.
    Knuuti, Juhani
    University of Turku, Finland.
    Kalliokoski, Kari
    University of Turku, Finland.
    Muscle free fatty-acid uptake associates to mechanical efficiency during exercise in humans2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, no AUG, article id 1171Article in journal (Refereed)
    Abstract [en]

    Intrinsic factors related to muscle metabolism may explain the differences in mechanical efficiency (ME) during exercise. Therefore, this study aimed to investigate the relationship between muscle metabolism and ME. Totally 17 healthy recreationally active male subjects were recruited and divided into efficient (EF; n=8) and inefficient (IE; n=9) groups, which were matched for age (mean±SD 24±2 vs. 23±2 yrs), BMI (23±1 vs. 23±2 kg m-2), physical acitivity levels (3.4±1.0 vs. 4.1±1.0 sessions/week), and V ̇O2peak (53±3 vs. 52±3 mL kg-1 min-1), respectively, but differed for ME at 45% of VO2peak intensity during submaximal bicycle ergometer test (EF 20.5±3.5 vs. IE 15.4±0.8 %, P < 0.001). Using Positron Emission Tomography, muscle blood flow (BF) and uptakes of oxygen (mVO2), fatty acids (FAU) and glucose (GU) were measured during dynamic submaximal knee-extension exercise. Workload-normalized BF (EF 35±14 vs. IE 34±11 mL 100g-1 min-1, P = 0.896), mVO2 (EF 4.1±1.2 vs. IE 3.9±1.2 mL 100g-1 min-1, P = 0.808), and GU (EF 3.1±1.8 vs. IE 2.6±2.3 μmol 100g-1 min-1, P = 0.641) as well as the delivery of oxygen, glucose, and fatty acids, as well as respiratory quotient were not different between the groups. However, FAU was significantly higher in EF than IE (3.1±1.7 vs. 1.7±0.6 μmol 100g-1 min-1, P < 0.047) and it also correlated with ME (r=0.56, P < 0.024) in the entire study group. EF group also demonstrated higher use of plasma fatty acids than IE, but no differences in use of plasma glucose and intramuscular energy sources were observed between the groups. These findings suggest that the effective use of plasma fatty acids is an important determinant of mechanical efficiency during exercise.

  • 42. Larsdotter-Mellstrom, Helena
    et al.
    Eriksson, Kerstin
    Liblikas, Ilme I.
    Wiklund, Christer
    Borg-Karlson, Anna-Karin
    KTH, School of Chemical Science and Engineering (CHE), Chemistry. University of Tartu, Estonia.
    Nylin, Soren
    Janz, Niklas
    Carlsson, Mikael A.
    It's All in the Mix: Blend-Specific Behavioral Response to a Sexual Pheromone in a Butterfly2016In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 7, article id 68Article in journal (Refereed)
    Abstract [en]

    Among insects, sexual pheromones are typically mixtures of two to several components, all of which are generally required to elicit a behavioral response. Here we show for the first time that a complete blend of sexual pheromone components is needed to elicit a response also in a butterfly. Males of the Green-veined White, Pieris napi, emit an aphrodisiac pheromone, citral, from wing glands. This pheromone is requisite for females to accept mating with a courting male. Citral is a mixture of the two geometric isomers geranial (E-isomer) and neral (Z-isomer) in an approximate 1:1 ratio. We found that both these compounds are required to elicit acceptance behavior, which indicates synergistic interaction between processing of the isomers. Using functional Ca2+ imaging we found that geranial and neral evoke significantly different but overlapping glomerular activity patterns in the antennal lobe, which suggests receptors with different affinity for the two isomers. However, these glomeruli were intermingled with glomeruli responding to, for example, plant-related compounds, i.e., no distinct subpopulation of pheromone-responding glomeruli as in moths and other insects. In addition, these glomeruli showed lower specificity than pheromone-activated glomeruli in moths. We could, however, not detect any mixture interactions among four identified glomeruli, indicating that the synergistic effect may be generated at a higher processing level. Furthermore, correlations between glomerular activity patterns evoked by the single isomers and the blend did not change over time.

  • 43.
    Larsdotter-Mellström, Helena
    et al.
    Stockholm University, Faculty of Science, Department of Zoology. The University of Western Australia, Australia.
    Eriksson, Kerstin
    Liblikas, Ilme
    Wiklund, Christer
    Stockholm University, Faculty of Science, Department of Zoology.
    Borg-Karlsson, Anna K.
    Nylin, Sören
    Stockholm University, Faculty of Science, Department of Zoology.
    Janz, Niklas
    Stockholm University, Faculty of Science, Department of Zoology.
    Carlsson, Mikael A.
    Stockholm University, Faculty of Science, Department of Zoology.
    It's All in the Mix: Blend-Specific Behavioral Response to a Sexual Pheromone in a Butterfly2016In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 7, article id 68Article in journal (Refereed)
    Abstract [en]

    Among insects, sexual pheromones are typically mixtures of two to several components, all of which are generally required to elicit a behavioural response. Here we show for the first time that a complete blend of sexual pheromone components is needed to elicit a response also in a butterfly. Males of the Green-veined White, Pieris napi, emit an aphrodisiac pheromone, citral, from wing glands. This pheromone is requisite for females to accept mating with a courting male. Citral is a mixture of the two geometric isomers geranial (E-isomer) and neral (Z-isomer) in an approximate 1:1 ratio. We found that both these compounds are required to elicit acceptance behaviour, which indicates synergistic interaction between processing of the isomers. Using functional Ca2+ imaging we found that geranial and neral evoke significantly different but overlapping glomerular activity patterns in the antennal lobe, which suggests receptors with different affinity for the two isomers. However, these glomeruli were intermingled with glomeruli responding to ,for example, plant-related compounds, i.e. no distinct subpopulation of pheromone-responding glomeruli as in moths and other insects. In addition, these glomeruli showed lower specificity than pheromone-activated glomeruli in moths. We could, however, not detect any mixture interactions among four identified glomeruli, indicating that the synergistic effect may be generated at a higher processing level. Furthermore, correlations between glomerular activity patterns evoked by the single isomers and the blend did not change over time.

  • 44. Lebreton, Sébastien
    et al.
    Carlsson, Mikael A.
    Stockholm University, Faculty of Science, Department of Zoology, Functional Morphology.
    Witzgall, Peter
    Insulin Signaling in the Peripheral and Central Nervous System Regulates Female Sexual Receptivity during Starvation in Drosophila2017In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 8, p. 1-9, article id 685Article in journal (Refereed)
    Abstract [en]

    Many animals adjust their reproductive behaviour according to nutritional state and food availability. Drosophila females for instance decrease their sexual receptivity following starvation. Insulin signalling, which regulates many aspects of insect physiology and behaviour, also affects reproduction in females. We show that insulin signalling is involved in the starvation-induced reduction in female receptivity. More specifically, females mutant for the insulin-like peptide 5 (dilp5) were less affected by starvation compared to the other dilp mutants and wild-type flies. Knocking-down the insulin receptor, either in all fruitless-positive neurons or a subset of these neurons dedicated to the perception of a male aphrodisiac pheromone, decreased the effect of starvation on female receptivity. Disrupting insulin signalling in some parts of the brain, including the mushroom bodies even abolished the effect of starvation. In addition, we identified fruitless-positive neurons in the dorso-lateral protocerebrum and in the mushroom bodies co-expressing the insulin receptor. Together, our results suggest that the interaction of insulin peptides determines the tuning of female sexual behaviour, either by acting on pheromone perception or directly in the central nervous system.

  • 45.
    Lewandowska, Marta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Bogatikov, Evgenii
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Hierlemann, Andreas R.
    Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland.
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Long-Term High-Density Extracellular Recordings Enable Studies of Muscle Cell Physiology2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 1424Article in journal (Refereed)
    Abstract [en]

    Skeletal (voluntary) muscle is the most abundant tissue in the body, thus making it an important biomedical research subject. Studies of neuromuscular transmission, including disorders of ion channels or receptors in autoimmune or genetic neuromuscular disorders, require high-spatial-resolution measurement techniques and an ability to acquire repeated recordings over time in order to track pharmacological interventions. Preclinical techniques for studying diseases of neuromuscular transmission can be enhanced by physiologic ex vivo models of tissue-tissue and cell-cell interactions. Here, we present a method, which allows tracking the development of primary skeletal muscle cells from myoblasts into mature contracting myotubes over more than 2 months. In contrast to most previous studies, the myotubes did not detach from the surface but instead formed functional networks between the myotubes, whose electrical signals were observed over the entire culturing period. Primary cultures of mouse myoblasts differentiated into contracting myotubes on a chip that contained an array of 26,400 platinum electrodes at a density of 3,265 electrodes per mm(2). Our ability to track extracellular action potentials at subcellular resolution enabled study of skeletal muscle development and kinetics, modes of spiking and spatio-temporal relationships between muscles. The developed system in turn enables creation of a novel electrophysiological platform for establishing ex vivo disease models.

  • 46.
    Liu, Zhengtao
    et al.
    Minist Publ Hlth, Key Lab Combined Multiorgan Transplantat, Hangzhou, Zhejiang, Peoples R China.;Key Lab Organ Transplantat Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Div Hepatobiliary & Pancreat Surg, Dept Surg, Affiliated Hosp 1,Sch Med, Hangzhou, Zhejiang, Peoples R China..
    Liang, Shuheng
    Women & Childrens Hosp Guangxi, Dept Pediat, Nanning, Peoples R China..
    Que, Shuping
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Zhou, Lin
    Minist Publ Hlth, Key Lab Combined Multiorgan Transplantat, Hangzhou, Zhejiang, Peoples R China.;Key Lab Organ Transplantat Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Div Hepatobiliary & Pancreat Surg, Dept Surg, Affiliated Hosp 1,Sch Med, Hangzhou, Zhejiang, Peoples R China..
    Zheng, Shusen
    Minist Publ Hlth, Key Lab Combined Multiorgan Transplantat, Hangzhou, Zhejiang, Peoples R China.;Key Lab Organ Transplantat Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Div Hepatobiliary & Pancreat Surg, Dept Surg, Affiliated Hosp 1,Sch Med, Hangzhou, Zhejiang, Peoples R China..
    Mardinogiu, Adil
    KTH, Centres, Science for Life Laboratory, SciLifeLab. Chalmers Univ Technol, Dept Biol & Biol Engn, Gothenburg, Sweden.;Kings Coll London, Dent Inst, Ctr Host Microbiome Interact, London, England..
    Meta-Analysis of Adiponectin as a Biomarker for the Detection of Metabolic Syndrome2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 1238Article, review/survey (Refereed)
    Abstract [en]

    Previous studies revealed the potential significance of circulating adiponectin levels with respect to the diagnosis and prediction of metabolic syndrome, but uncertainty has been noted across different cohorts. Systematic evaluation was performed for diagnostic accuracy and predictivity of adiponectin variation for metabolic syndrome in enrolled studies including 1,248 and 6,020 subjects, respectively. Adiponectin can identify metabolic syndrome with moderate accuracy (area under the curve = 0.81, 95% CI: 0.77-0.84). Heterogeneity analysis revealed that an increasing index of insulin resistance was independently associated with improving the performance of adiponectin upon metabolic syndrome diagnosis (ratio of diagnostic odds ratio = 3.89, 95% CI: 1.13-13.9). In addition, reductions in adiponectin were associated with increasing metabolic syndrome incidence in a linear dose-response manner. The risk of hypoadiponectinemia with metabolic syndrome was especially increased in men (P < 0.05). Further Mendelian randomization analysis identified that the amplified risk could be attributed to increased susceptibility (up to 7%) to insulin resistance compared with women. In conclusion, adiponectin measurement might have potential benefits in the detection of metabolic syndrome. Factors that affect insulin resistance should be considered for adjustment in future assessments.

  • 47.
    Lundqvist, Martin H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Almby, Kristina E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Abrahamsson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Is the Brain a Key Player in Glucose Regulation and Development of Type 2 Diabetes?2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 457Article, review/survey (Refereed)
    Abstract [en]

    Ever since Claude Bernards discovery in the mid 19th-century that a lesion in the floor of the third ventricle in dogs led to altered systemic glucose levels, a role of the CNS in whole-body glucose regulation has been acknowledged. However, this finding was later overshadowed by the isolation of pancreatic hormones in the 20th century. Since then, the understanding of glucose homeostasis and pathology has primarily evolved around peripheral mechanism. Due to scientific advances over these last few decades, however, increasing attention has been given to the possibility of the brain as a key player in glucose regulation and the pathogenesis of metabolic disorders such as type 2 diabetes. Studies of animals have enabled detailed neuroanatomical mapping of CNS structures involved in glucose regulation and key neuronal circuits and intracellular pathways have been identified. Furthermore, the development of neuroimaging techniques has provided methods to measure changes of activity in specific CNS regions upon diverse metabolic challenges in humans. In this narrative review, we discuss the available evidence on the topic. We conclude that there is much evidence in favor of active CNS involvement in glucose homeostasis but the relative importance of central vs. peripheral mechanisms remains to be elucidated. An increased understanding of this field may lead to new CNS-focusing pharmacologic strategies in the treatment of type 2 diabetes.

  • 48.
    Mardinoglu, Adil
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nielsen, Jens
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Editorial: The Impact of Systems Medicine on Human Health and Disease2016In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 7, article id 552Article in journal (Other academic)
  • 49.
    Marseglia, Anna
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Medical University, China.
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Fabbri, Cristina
    Berendsen, Agnes A. M.
    Bialecka-Debek, Agata
    Jennings, Amy
    Gillings, Rachel
    Meunier, Nathalie
    Caumon, Elodie
    Fairweather-Tait, Susan
    Pietruszka, Barbara
    De Groot, Lisette C. P. G. M.
    Santoro, Aurelia
    Franceschi, Claudio
    Effect of the NU-AGE Diet on Cognitive Functioning in Older Adults: A Randomized Controlled Trial2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 349Article in journal (Refereed)
    Abstract [en]

    Background: Findings from animal and epidemiological research support the potential neuroprotective benefits from healthy diets. However, to establish diet neuroprotective causal relations, evidence from dietary intervention studies is needed. NU-AGE is the first multicenter intervention assessing whether a diet targeting health in aging can counteract the age-related physiological changes in different organs, including the brain. In this study, we specifically investigated the effects of NU-AGE's dietary intervention on age related cognitive decline.

    Materials and Methods: NU-AGE randomized trial (NCT01754012, clinicaltrials.gov) included 1279 relatively healthy older-adults, aged 65-79 years, from five European centers. Participants were randomly allocated into two groups: control (n = 638), following a habitual diet; and, intervention (n = 641), given individually tailored dietary advice (NU-AGE diet). Adherence to the NU-AGE diet was measured over follow-up, and categorized into tertiles (low, moderate, high). Cognitive function was ascertained at baseline and at 1-year follow-up with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-Neuropsychological Battery and five additional domain-specific single cognitive tests. The raw scores from the CERAD subtests [excluding the Mini-Mental State Examination (MMSE)] and the single tests were standardized into Z-scores. Global cognition (measured with MMSE and CERAD total score), and five cognitive domains (perceptual speed, executive function, episodic memory, verbal abilities, and constructional praxis) were created. Cognitive changes as a function of the intervention were analyzed with multivariable mixed effects models.

    Results: After the 1-year follow-up, 571 (89.1%) controls and 573 (89.8%) from the intervention group participated in the post-intervention assessment. Both control and intervention groups showed improvements in global cognition and in all cognitive domains after 1 year, but differences in cognitive changes between the two groups were not statistically significant. However, participants with higher adherence to the NU-AGE diet showed statistically significant improvements in global cognition [beta 0.20 (95%CI 0.004, 0.39), p-value = 0.046] and episodic memory [beta 0.15 (95%Cl 0.02, 0.28), p-value = 0.025] after 1 year, compared to those adults with lower adherence.

    Discussion: High adherence to the culturally adapted, individually tailored, NU-AGE diet could slow down age-related cognitive decline, helping to prevent cognitive impairment and dementia.

  • 50.
    Marsland, Finn
    et al.
    Univ Canberra, Canberra, ACT, Australia; Australian Inst Sport, Canberra, ACT, Australia.
    Anson, Judith
    Univ Canberra, Canberra, ACT, Australia.
    Waddington, Gordon
    Univ Canberra, Canberra, ACT, Australia.
    Holmberg, Hans-Christer
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. UiT Arctic Univ Norway, Sch Sport Sci, Tromso, Norway.
    Chapman, Dale W.
    Univ Canberra, Canberra, ACT, Australia; Australian Inst Sport, Canberra, ACT, Australia.
    Macro-Kinematic Differences Between Sprint and Distance Cross-Country Skiing Competitions Using the Classical Technique2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, no MAY, article id 570Article in journal (Refereed)
    Abstract [en]

    We compare the macro-kinematics of six elite female cross-country skiers competing in 1.1-km Sprint and 10.5-km Distance classical technique events on consecutive days under similar weather and track conditions. The relative use of double pole (DP), kick-double pole (KDP), diagonal stride (DS), tucking (Tuck) and turning (Turn) sub-techniques, plus each technique's respective velocities, cycle lengths and cycle rates were monitored using a single micro-sensor unit worn by each skier during the Sprint qualification, semi-final and finals, and multiple laps of the Distance race. Over a 1.0-km section of track common to both Sprint and Distance events, the mean race velocity, cyclical sub-technique velocities, and cycle rates were higher during the Sprint race, while Tuck and Turn velocities were similar. Velocities with KDP and DS on the common terrain were higher in the Sprint (KDP +12%, DS +23%) due to faster cycle rates (KDP +8%, DS +11 %) and longer cycle lengths (KDP +5%, DS +10%), while the DP velocity was higher (+8%) with faster cycle rate (+16%) despite a shorter cycle length (-9%). During the Sprint the percentage of total distance covered using DP was greater (+15%), with less use of Tuck (-19%). Across all events and rounds, DP was the most used sub-technique in terms of distance, followed by Tuck, DS, Turn and KDP. KDP was employed relatively little, and during the Sprint by only half the participants. Tuck was the fastest sub-technique followed by Turn, DP, KDP, and DS, These findings reveal differences in the macro-kinematic characteristics and strategies utilized during Sprint and Distance events, confirm the use of higher cycle rates in the Sprint, and increase our understanding of the performance demands of cross-country skiing competition.

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