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  • 51.
    Eriksson, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Bergström, Fredrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Unconscious working memory engages the prefrontal cortex2013In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 25, no Suppl., p. S74-S74Article in journal (Other academic)
  • 52.
    Eriksson, S
    et al.
    Department of Physiology, Karolinska Institute, Stockholm, Sweden.
    Andersson, B
    Gunnarsson, Ulf
    Department of Physiology, Karolinska Institute, Stockholm, Sweden.
    Rundgren, M
    Hypertension and thirst outlasting renal vasoconstriction as effects of a brief evaluation of systemic angiotensin II in sheep.1994In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 150, no 2, p. 181-8Article in journal (Refereed)
    Abstract [en]

    The influence of 10 min intracarotid (i.c.) and intravenous (i.v.) infusions of angiotensin II (Ang II; 20 pmol kg-1 min-1) on carotid blood pressure (cBP) and renal blood flow (RBF) was studied in unanaesthetized ewes without and with pre-treatment with the alpha 1- and beta-adrenoceptor blocker labetalol. RBF was also monitored during 30 min intracerebroventricular (ICV) infusions of Ang II at 2 pmol kg-1 min-1. The i.c. infusions of Ang II induced about 50 mmHg rise in cBP. A steep decline occurred during 5 min post-infusion, followed by a much slower reduction with the cBP remaining above control level at 40 min post-infusion. The pressure elevation induced by i.v. Ang II was less pronounced but exhibited a similar pattern. Labetalol significantly reduced the pressor response to i.c. as well as i.v. Ang II. The i.c. and i.v. infusions of Ang II conspicuously reduced the RBF regardless of whether the ewes were labetalol-treated or not. At 5 min after the infusions RBF had returned to control level. The ICV infusions did not influence the RBF. Ang II i.c. elicited thirst in 50% of the ewes with the urge to drink remaining at 40 min post-infusion. The dipsogenic response was not reduced by labetalol pretreatment. The results imply that no cerebral component contributes to the reduction in RBF induced by systemic Ang II. However, a centrally mediated action seems to be the cause of the long-lasting post-infusion cBP elevation and dipsogenic response.(ABSTRACT TRUNCATED AT 250 WORDS)

  • 53.
    Fischer, M Dominik
    et al.
    University of Pennsylvania School of Medicine.
    Gorospe, J Rafael
    George Washington University, Washington.
    Felder, Edward
    University of Pennsylvania School of Medicine, Philadelphia.
    Bogdanovich, Sasha
    University of Pennsylvania School of Medicine.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Ahima, Rexford S
    University of Pennsylvania School of Medicine, Philadelphia.
    Rubinstein, Neal A
    University of Pennsylvania School of Medicine, Philadelphia.
    Hoffman, Eric P
    George Washington University, Washington.
    Khurana, Tejvir S
    University of Pennsylvania School of Medicine.
    Expression profiling reveals metabolic and structural components of extraocular muscles2002In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 9, no 2, p. 71-84Article in journal (Refereed)
    Abstract [en]

    The extraocular muscles (EOM) are anatomically and physiologically distinct from other skeletal muscles. EOM are preferentially affected in mitochondrial myopathies, but spared in Duchenne's muscular dystrophy. The anatomical and pathophysiological properties of EOM have been attributed to their unique molecular makeup: an allotype. We used expression profiling to define molecular features of the EOM allotype. We found 346 differentially expressed genes in rat EOM compared with tibialis anterior, based on a twofold difference cutoff. Genes required for efficient, fatigue-resistant, oxidative metabolism were increased in EOM, whereas genes for glycogen metabolism were decreased. EOM also showed increased expression of genes related to structural components of EOM such as vessels, nerves, mitochondria, and neuromuscular junctions. Additionally, genes related to specialized functional roles of EOM such as the embryonic and EOM-specific myosin heavy chains and genes for muscle growth, development, and/or regeneration were increased. The EOM expression profile was validated using biochemical, structural, and molecular methods. Characterization of the EOM expression profile begins to define gene transcription patterns associated with the unique anatomical, metabolic, and pathophysiological properties of EOM.

  • 54.
    Fjellman-Wiklund, Anncristine
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Grip, Helena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Karlsson, J Stefan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Sundelin, Gunnevi
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    EMG trapezius muscle activity pattern in string players: Part I - Is there variability in the playing technique?2004In: International Journal of Industrial Ergonomics, ISSN 0169-8141, E-ISSN 1872-8219, Vol. 33, no 4, p. 347-356Article in journal (Refereed)
  • 55. Flanagan, J R
    et al.
    King, S
    Wolpert, D M
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Sensorimotor prediction and memory in object manipulation2001In: Canadian journal of experimental psychology, ISSN 1196-1961, E-ISSN 1878-7290, Vol. 55, no 2, p. 87-95Article in journal (Refereed)
    Abstract [en]

    When people lift objects of different size but equal weight, they initially employ too much force for the large object and too little force for the small object. However, over repeated lifts of the two objects, they learn to suppress the size-weight association used to estimate force requirements and appropriately scale their lifting forces to the true and equal weights of the objects. Thus, sensorimotor memory from previous lifts comes to dominate visual size information in terms of force prediction. Here we ask whether this sensorimotor memory is transient, preserved only long enough to perform the task, or more stable. After completing an initial lift series in which they lifted equally weighted large and small objects in alternation, participants then repeated the lift series after delays of 15 minutes or 24 hours. In both cases, participants retained information about the weights of the objects and used this information to predict the appropriate fingertip forces. This preserved sensorimotor memory suggests that participants acquired internal models of the size-weight stimuli that could be used for later prediction.

  • 56.
    Flanagan, J Randall
    et al.
    Queen's University, Kingston, Ontario K7L 3N6.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Action plans used in action observation2003In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, ISSN 1476-4687, Vol. 424, no 6950, p. 769-771Article in journal (Refereed)
    Abstract [en]

    How do we understand the actions of others? According to the direct matching hypothesis, action understanding results from a mechanism that maps an observed action onto motor representations of that action. Although supported by neurophysiological and brain-imaging studies, direct evidence for this hypothesis is sparse. In visually guided actions, task-specific proactive eye movements are crucial for planning and control. Because the eyes are free to move when observing such actions, the direct matching hypothesis predicts that subjects should produce eye movements similar to those produced when they perform the tasks. If an observer analyses action through purely visual means, however, eye movements will be linked reactively to the observed action. Here we show that when subjects observe a block stacking task, the coordination between their gaze and the actor's hand is predictive, rather than reactive, and is highly similar to the gaze-hand coordination when they perform the task themselves. These results indicate that during action observation subjects implement eye motor programs directed by motor representations of manual actions and thus provide strong evidence for the direct matching hypothesis.

  • 57.
    Flanagan, J Randall
    et al.
    Department of Psychology, Queen's University, Kingston, Ontario, Canada, Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.
    Rotman, Gerben
    Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.
    Reichelt, Andreas F
    Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    The role of observers' gaze behaviour when watching object manipulation tasks: predicting and evaluating the consequences of action2013In: Philosophical Transactions of the Royal Society of London. Biological Sciences, ISSN 0962-8436, E-ISSN 1471-2970, Vol. 368, no 1628, p. 20130063-Article in journal (Refereed)
    Abstract [en]

    When watching an actor manipulate objects, observers, like the actor, naturally direct their gaze to each object as the hand approaches and typically maintain gaze on the object until the hand departs. Here, we probed the function of observers' eye movements, focusing on two possibilities: (i) that observers' gaze behaviour arises from processes involved in the prediction of the target object of the actor's reaching movement and (ii) that this gaze behaviour supports the evaluation of mechanical events that arise from interactions between the actor's hand and objects. Observers watched an actor reach for and lift one of two presented objects. The observers' task was either to predict the target object or judge its weight. Proactive gaze behaviour, similar to that seen in self-guided action-observation, was seen in the weight judgement task, which requires evaluating mechanical events associated with lifting, but not in the target prediction task. We submit that an important function of gaze behaviour in self-guided action observation is the evaluation of mechanical events associated with interactions between the hand and object. By comparing predicted and actual mechanical events, observers, like actors, can gain knowledge about the world, including information about objects they may subsequently act upon.

  • 58.
    Flanagan, J Randall
    et al.
    Queen's University, Kingston, Ontario.
    Vetter, Philipp
    University College London, Queen Square, London.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Wolpert, Daniel M
    University College London, Queen Square, London.
    Prediction precedes control in motor learning2003In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 13, no 2, p. 146-150, Article Number: PII S0960-9822(03)00007-1Article in journal (Refereed)
    Abstract [en]

    Skilled motor behavior relies on the brain learning both to control the body and predict the consequences of this control. Prediction turns motor commands into expected sensory consequences, whereas control turns desired consequences into motor commands. To capture this symmetry, the neural processes underlying prediction and control are termed the forward and inverse internal models, respectively. Here, we investigate how these two fundamental processes are related during motor learning. We used an object manipulation task in which subjects learned to move a hand-held object with novel dynamic properties along a prescribed path. We independently and simultaneously measured subjects' ability to control their actions and to predict their consequences. We found different time courses for predictor and controller learning, with prediction being learned far more rapidly than control. In early stages of manipulating the object, subjects could predict the consequences of their actions, as measured by the grip force they used to grasp the object, but could not generate appropriate actions for control, as measured by their hand trajectory. As predicted by several recent theoretical models of sensorimotor control, our results indicate that people can learn to predict the consequences of their actions before they can learn to control their actions.

  • 59.
    Flodgren, Gerd
    et al.
    Centre for Musculoskeletal Research, University of Gävle, Sweden.
    Crenshaw, AG
    Centre for Musculoskeletal Research, University of Gävle, Sweden.
    Gref, Margareta
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Fahlström, Martin
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine.
    Changes in interstitial noradrenaline, trapezius muscle activity and oxygen saturation during low-load work and recovery2009In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 107, no 1, p. 31-42Article in journal (Refereed)
    Abstract [en]

    Both physical as well as mental demands result in an increased activity in the sympathetic nervous system (SNS) with changes in blood-pressure and heart-rate. Through local release of catecholamines, e.g. noradrenaline (NAd) SNS exerts various actions at the muscle level. The aims of this study were to investigate the effects of low-load repetitive work alone and in combination with mental demands on local muscle interstitial noradrenaline concentration [NAd]i, muscle activity and oxygenation, assessed with microdialysis, surface electromyography, and near-infrared spectroscopy, respectively. Healthy females (n = 15) were exposed to (1) 30 min repetitive work (RW) and (2) 30 min repetitive work with superimposed mental load (RWML) on two different occasions. Muscle [NAd]i and muscle activity increased significantly in response to RW, but did not increase further during RWML. For RW, [NAd]i was found to be inversely correlated to muscle activity. Oxygenation decreased significantly during work, independently of occasion. Our findings indicate that low-load work causes significantly increased trapezius muscle [NAd]i in healthy females, and short periods of superimposed mental load do not add to this increase and further, that both muscle activity and oxygenation were unaffected by the superimposed mental load.

  • 60.
    Fridén, Jan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. the Department of Physiology III, Karolinska Institutet, Stockholm, Sweden.
    Exercise-induced muscle soreness: a qualitative and quantitative study of human muscle morphology and function1983Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Exercise-induced muscle soreness is characterized by stiffness, tenderness and pain during active movements and weakness of the affected musculature the days after unusually or particularly heavy work. The most pronounced subjective symptoms do not arise immediately but rather between a couple of hours to some days after the exercise (a delayed-onset of muscle soreness), the intensity of pain is greatest about 48 hours after the work. A particular association exists between muscle soreness and eccentric contractions. Despite the fact that muscle soreness is a well known phenomenon in the sphere of sports as well as working life, the pathophysiological mechanisms underlying this are still not understood.

    In the present study a detailed analysis of human muscle fibre population structure after high tension work (eccentric exercise) that gave rise to muscle soreness, was carried out. The objective was to elucidate how fibres of different types are influenced by repeated muscle contractions reaching extreme tension levels using qualitative and quantitative light and electron microscopic techniques. It was hoped that such morphological analysis would provide a basis for discussion of possible causes for muscle soreness. The muscle function after the work was measured by isokinetic methods.

    To improve the basis for the ultrastructural analysis the fibre populations in untrained and en­durance trained human m. vastus lateralis of age-matched individuals were classified into different fibre type groups according to their ultrastructure. The selective glycogen depletion from Type 1 fibres seen after long term submaximal work, visualized electron microscopically with PA-TSC-SP staining, substantiated the usefulness of the appearance of the M-band to differentiate between fibre types. Stereological data showed that neither volume density of mitochondria nor of lipid droplets provide sufficient criteria to differentiate between fibre types.

    After an eccentric exercise regimen sore muscles (m. soleus or m. vastus lateralis) showed disturb­ances of the cross striated band pattern. Fibres with disorganized myofibrillar material made up 1/3, 1/2 and 1/10 of the analysed material, 1 hour, 3 and 6 days after exercise, respectively. The myofibril­lar lesions were preferably localized in the Z-band. This showed streaming, broadening and sometimes total disruption. The Type 2 fibres were most affected.

    The reduction of strength was greatest with the most rapid contractions. Strength remained de­creased the period when the structural damage was most pronounced. Eight weeks of eccentric muscle training reduced all the above negative effects.

    The results indicate that the Z-disc constitute the weak link in the myofibrillar contractile chain at high muscle tensions. It is suggested that the myofibrillar lesions are a direct result of mechanical tearing. Rupture of myofibrils is thought to result in formation of protein components and a con- sequental release of protein bound ions that via osmosis result in oedema and soreness. Training, using eccentric contractions over a long period of time leads to adaptations at the fibre level by a reorgani­zation of the contractile apparatus as well as an optimization of nervous coordination.

  • 61.
    Geithner, Christina A.
    et al.
    Department of Organizational Leadership, Gonzaga University.
    Molenaar, Claire E.
    The School of Physical Therapy, Regis University.
    Henriksson, Tommy
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Fjellman-Wiklund, Anncristine
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Gilenstam, Kajsa
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Relative Age Effects in Women’s Ice Hockey: Contributions of Body Size and Maturity Status2018In: Women in Sport & Physical Activity Journal, ISSN 1063-6161, E-ISSN 1938-1581, Vol. 26, no 2, p. 124-133Article in journal (Refereed)
    Abstract [en]

    Research on relative age effects (RAEs) in women’s ice hockey is lacking data on participant characteristics, particularly body size and maturity status. The purposes of our study were to investigate RAEs in women’s ice hockey players from two countries, and to determine whether RAE patterns could be explained by chronological age, body size, and maturity status. Participants were 54 Swedish elite and 63 Canadian university players. Birthdates were coded by quartiles (Q1–Q4). Weight and height were obtained, and body mass index and chronological age were calculated for each player. Players recalled age at menarche, and maturity status was classified as early, average, or late relative to population-specific means. Chi-square (χ2), odds ratios (OR), 95% confidence intervals (CI) and effect sizes (Cohen’s w) were calculated using population data across quartiles and for pairwise comparisons between quartiles. Descriptive statistics and MANOVAs were run by quartile and by country. Significant RAEs were found for Canadian players across quartiles (p < .05), along with a Q2 phenomenon (Q2: Q3, Q2: Q4, p < .05). Swedish players were overrepresented in Q3 (Q3: Q4, p < .05). Q4 was significantly underrepresented in both countries (p < .05). The oldest, earliest maturing, and shortest players in both countries were clustered in Q2, whereas the next oldest and latest maturing Swedish players were found in Q3. Age, physical factors, and interactions may contribute to overrepresentations in Q2 and Q3. These findings do not suggest the same bias for greater relative age and maturity found in male ice hockey.

  • 62.
    Gerdle, Björn
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Leisure and muscular performance in health and disease: a study of 40-64-year-old northern Swedes1985Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Categories and frequencies of leisureactivities employed by 156 randomly selected males and females aged 40-44, 50-54, 60-64 were investigated by structured interviews and were related to leisuresatisfaction, to experienced health and socio-economic status. In equal numbers (15) of males and females from each group and in 24 males (60 +_6 years) with intermittent claudication (Cl) isokinetic plantar flexion performance was investigated with registrations of peak torque (PT), contractional work (CW), active range-of-motion (RoM) and integrated electromyograms from all threee triceps surae heads. Subjects performed a few maximum plantarflexions at different velocities of angular motion and also up to 200 consecutive plantar flexions at 60 °/s. The males aged 40-44 were re -investigated after two years additionally using electromyographic power frequency analyses.

    Leisure choice was mainly age and sex independent and extensively included outdoor activities. Leisure satisfaction was positively associated with relative frequency of activities. Symptoms of bodily discomfort, in particular backpain, were quite common and apparently caused relatively low level of mutual leisure activities. Thus, with in this age span, leisure activities appear rather rigid but often successfully, adhered to . Common ailments influence partnership mutuality negatively.

    Plantar flexion PT and CW are adequately p re dicta ble by sex, age and crural circumference. Uniformly a 3:2 male/female ratio characterizes mechanical output and iEMG. The latter is velocity independent. Output decreases with increasing age. Hence the output/excitation balance (CW/iEMG) is age, but not sex, dependent. CI-patients produce less PT and CW than do controls. Independently of this disease, of age and sex, PT and CW describe parallel negative exponential functions of velocity.

    During repeated manoeuvres plantar flexion output and iEMG initially drop, there after to maintain nearly steady-state levels. Throughout up to 200 contractions CW/iEMG was unaltered in the clinically healthy. Test/re-test with two years interval yielded nearly identical results. Leftshifts in mean power frequency in parallel with output-drop imply that the latter probably is due to FT-motor unit fatigue. For CW, but not for PT, the drop became slower and the (relative) steady-state level higher with increasing age, indicating significant increase in endurance with age. In the Cl-patients, output, but not excitation, decreased after a few repititions. Therefore, CW/iEMG fell dramatically, implying intramuscular fatigue. Taken together with findings of close associations between total cumulated work and measured/expected maximum walking tole rance it is suggested that measurements of CW and calculations of CW/iEMG are of clinical value.

  • 63. Gerdle, Björn
    et al.
    Östlund, Nils
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Department of Biomedical Engineering and Informatics, University Hospital, Umeå, Sweden.
    Grönlund, Christer
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Department of Biomedical Engineering and Informatics, University Hospital, Umeå, Sweden.
    Roeleveld, Karin
    Karlsson, Stefan
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Department of Biomedical Engineering and Informatics, University Hospital, Umeå, Sweden.
    Firing rate and conduction velocity of single motor units in the trapezius muscle in fibromyalgia patients and healthy controls2008In: Journal of Electromyography & Kinesiology, ISSN 1050-6411, E-ISSN 1873-5711, Vol. 18, no 5, p. 707-716Article in journal (Refereed)
    Abstract [en]

    Fibromyalgia is a common chronic pain condition in the population (2-4%), which often is associated with prominent negative consequences with respect to participation in daily activities. There are several reports in the literature concerning the effects of acute experimental pain on motor control. However, a more heterogeneous picture exists in the literature with respect to whether chronic pain conditions affect motor control. This study compares firing rate and conduction velocity (CV) of single motor units (MUs) in the trapezius muscle of fibromyalgia patients (FM) and healthy controls (CON). Multi-channel surface electromyography was used to estimate both MU firing rate and CV because this technique allows simultaneous estimation of both these variables and the measurements are easy and non-invasive. In this study, 29 FM and 30 CON subjects participated and performed isometric shoulder elevations using weights up to 4 kg. No significant differences in the firing rate of MUs in the trapezius muscle were found between the FM and CON groups (95% confidence interval was -1.9 and 1.3 pulses per second). There were no significant differences in CV between the groups at 1 and 2 kg load. However, the FM group had significantly higher CV in contractions without external load (p=0.004). We were unable to confirm the pain-adaptation model since no differences in firing rate between the two groups were found. CV was significantly higher in FM than in healthy controls; this might be due to alterations in histopathology and microcirculation.

  • 64.
    Ghorbani, Ramin
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Real-time breath gas analysis of carbon monoxide: laser-based detection and pulmonary gas exchange modeling2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Breath gas analysis is a promising approach for non-invasive medical diagnostics and physiological monitoring. Real-time, breath-cycle resolved biomarker detection facilitates data interpretation and has the potential to improve the diagnostic value of breath tests as exhalation profiles carry spatiotemporal information about biomarker origin and gas exchange in the respiratory tract. This thesis presents and scrutinizes a novel methodology for the analysis of real-time breath data, where single-exhalation profiles are simulated using a pulmonary gas exchange model and least-squares fitted to measured expirograms to extract airway and alveolar contributions and diffusing capacities. The methodology is demonstrated on exhaled breath carbon monoxide (eCO), a candidate biomarker for oxidative stress and respiratory diseases. The thesis mainly covers (1) the construction of a compact optical sensor based on tunable diode laser absorption spectroscopy (TDLAS) in the mid-infrared region (4.7 μm) for selective and precise real-time detection of CO in breath and ambient air (detection limit 9 ± 5 ppb at 0.1 s), (2) the design of an advanced online breath sampling system, (3) the implementation of a trumpet model with axial diffusion (TMAD) to simulate the CO gas exchange, and (4) the application of extended eCO analysis in clinical studies to establish the healthy non-smoker baseline of the eCO parameters and to study the response to CO and wood smoke exposure. It is shown that the TMAD adequately describes the gas exchange during systemic CO elimination for different breathing patterns, and that there is no difference between eCO parameters from mouth- and nose exhalations. Expirogram shape and eCO parameters exhibit a dependence on the exhalation flow rate, but for a given breathing maneuverer, the parameters lie in a narrow range. Airway CO is close to and correlates with ambient air CO, indicating negligible airway production in the healthy population. The alveolar diffusing capacity is independent of endogenous CO, even after exposure to elevated exogenous CO, and could be used to assess lung diffusion abnormalities. Compared to CO exposure, no clear additional effect of exposure to wood smoke particles on eCO is observed. The discrimination between endogenous and exogenous CO sources remains a challenge.

  • 65.
    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.
    Extended breath CO analysis: baseline and diurnal variation of pulmonary gas exchange parametersManuscript (preprint) (Other academic)
  • 66.
    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.

  • 67.
    Ghorbani, Ramin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Schmidt, Florian M.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Fitting of single-exhalation profiles using a pulmonary gas exchange model: application to carbon monoxide2019In: Journal of Breath Research, ISSN 1752-7155, E-ISSN 1752-7163, Vol. 13, no 2, article id 026001Article in journal (Refereed)
    Abstract [en]

    Real-time breath gas analysis coupled to gas exchange modeling is emerging as promising strategy to enhance the information gained from breath tests. It is shown for exhaled breath carbon monoxide (eCO), a potential biomarker for oxidative stress and respiratory diseases, that a weighted, nonlinear least-squares fit of simulated to measured expirograms can be used to extract physiological parameters, such as airway and alveolar concentrations and diffusing capacities. Experimental CO exhalation profiles are acquired with high time-resolution and precision using mid-infrared tunable diode laser absorption spectroscopy and online breath sampling. A trumpet model with axial diffusion is employed to generate eCO profiles based on measured exhalation flow rates and volumes. The concept is demonstrated on two healthy non-smokers exhaling at a flow rate of 250 ml s−1 during normal breathing and at 120 ml s−1 after 10 s of breath-holding. The obtained gas exchange parameters of the two subjects are in a similar range, but clearly distinguishable. Over a series of twenty consecutive expirograms, the intra-individual variation in the alveolar parameters is less than 6%. After a 2 h exposure to 10 ± 2 ppm CO, end-tidal and alveolar CO concentrations are significantly increased (by factors of 2.7 and 4.9 for the two subjects) and the airway CO concentration is slightly higher, while the alveolar diffusing capacity is unchanged compared to before exposure. Using model simulations, it is found that a three-fold increase in maximum airway CO flux and a reduction in alveolar diffusing capacity by 60% lead to clearly distinguishable changes in the exhalation profile shape. This suggests that extended breath CO analysis has clinical relevance in assessing airway inflammation and chronic obstructive pulmonary disease. Moreover, the novel methodology contributes to the standardization of real-time breath gas analysis.

  • 68.
    Ghorbani, Ramin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Schmidt, Florian M.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    ICL-based TDLAS sensor for real-time breath gas analysis of carbon monoxide isotopes2017In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 25, no 11, p. 12743-12752Article in journal (Refereed)
    Abstract [en]

    We present a compact sensor for carbon monoxide (CO) in air and exhaled breath based on a room temperature interband cascade laser (ICL) operating at 4.69 µm, a low-volume circular multipass cell and wavelength modulation absorption spectroscopy. A fringe-limited (1σ) sensitivity of 6.5 × 10−8 cm−1Hz-1/2 and a detection limit of 9 ± 5 ppbv at 0.07 s acquisition time are achieved, which constitutes a 25-fold improvement compared to direct absorption spectroscopy. Integration over 10 s increases the precision to 0.6 ppbv. The setup also allows measuring the stable isotope 13CO in breath. We demonstrate quantification of indoor air CO and real-time detection of CO expirograms from healthy non-smokers and a healthy smoker before and after smoking. Isotope ratio analysis indicates depletion of 13CO in breath compared to natural abundance.

  • 69.
    Ghorbani, Ramin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Schmidt, Florian M.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Real-time breath gas analysis of CO and CO2 using an EC-QCL2017In: Applied physics. B, Lasers and optics (Print), ISSN 0946-2171, E-ISSN 1432-0649, Vol. 123, no 5, article id 144Article in journal (Refereed)
    Abstract [en]

    Real-time breath gas analysis is a promising, non-invasive tool in medical diagnostics, and well-suited to investigate the physiology of carbon monoxide (CO), a potential biomarker for oxidative stress and respiratory diseases. A sensor for precise, breath-cycle resolved, simultaneous detection of exhaled CO (eCO) and carbon dioxide (eCO2) was developed based on a continuous wave, external-cavity quantum cascade laser (EC-QCL), a low-volume multi-pass cell and wavelength modulation spectroscopy. The system achieves a noise-equivalent (1σ) sensitivity of 8.5 × 10−8 cm−1 Hz−1/2 and (2σ) detection limits of 9 ± 2 ppbv and 650 ± 7 ppmv at 0.14 s spectrum acquisition time for CO and CO2, respectively. Integration over 15 s yields a precision of 0.6 ppbv for CO. The fact that the eCO2 expirograms measured by capnography and laser spectroscopy have essentially identical shape confirms true real-time detection. It is found that the individual eCO exhalation profiles from healthy non-smokers have a slightly different shape than the eCO2 profiles and exhibit a clear dependence on exhalation flow rate and breath-holding time. Detection of indoor air CO and broadband breath profiling across the 93 cm−1 mode-hop-free tuning range of the EC-QCL are also demonstrated.

  • 70.
    Gilenstam, Kajsa
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Henriksson-Larsén, Karin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Thorsen, Kim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Influence of stick stiffness and puck weight on puck velocity during slap shots in women's ice hockey2009In: Sports Engineering, ISSN 1369-7072, E-ISSN 1460-2687, Vol. 11, no 3, p. 103-107Article in journal (Refereed)
    Abstract [en]

    Previous studies have found that reduced stick stiffness increases puck velocity in young male ice hockey players. This study investigates the hypothesis that female players are disadvantaged by using equipment that is designed for taller and stronger players. The purpose of this study was to investigate if stick flexibility and puck weight affect puck velocity in standing slap shots performed by female ice hockey players. There was a significant increase in puck velocity (4.1% p=0.037) when stick stiffness and puck weight were reduced. ANOVA revealed that there was a significant correlation between stick, puck and the participant herself (R2=0.987). Spearman’s correlation analysis revealed that participants with higher puck velocities benefitted the most when the stick flexibility and puck weight were reduced (r=0.648; p=0.043). It was concluded that decreased stick stiffness and puck weight increased puck velocity in standing slap shots for female ice hockey players.

  • 71.
    Gilenstam, Kajsa M.
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Social Sciences, Umeå Centre for Gender Studies (UCGS).
    Thorsen, Kim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Henriksson-Larsén, Karin B.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Physiological Correlates of Skating Performance in Women's and Men's Ice Hockey2011In: Journal of Strength and Conditioning Research, ISSN 1064-8011, E-ISSN 1533-4287, Vol. 25, no 8, p. 2133-2142Article in journal (Refereed)
    Abstract [en]

    The purpose of the current investigation was to identify relationships between physiological off-ice tests and on-ice performance in female and male ice hockey players on a comparable competitive level. Eleven women, 24 ± 3.0 years, and 10 male ice hockey players, 23 ± 2.4 years, were tested for background variables: height, body weight (BW), ice hockey history, and lean body mass (LBM) and peak torque (PT) of the thigh muscles, [latin capital V with dot above]o2peak and aerobic performance (Onset of Blood Lactate Accumulation [OBLA], respiratory exchange ratio [RER1]) during an incremental bicycle ergometer test. Four different on-ice tests were used to measure ice skating performance. For women, skating time was positively correlated (p < 0.05) to BW and negatively correlated to LBM%, PT/BW, OBLA, RER 1, and [latin capital V with dot above]o2peak (ml O2·kg-1 BW-1·min-1) in the Speed test. Acceleration test was positively correlated to BW and negatively correlated to OBLA and RER 1. For men, correlation analysis revealed only 1 significant correlation where skating time was positively correlated to [latin capital V with dot above]o2peak (L O2·min-1) in the Acceleration test. The male group had significantly higher physiological test values in all variables (absolute and relative to BW) but not in relation to LBM. Selected off-ice tests predict skating performance for women but not for men. The group of women was significantly smaller and had a lower physiological performance than the group of men and were slower in the on-ice performance tests. However, gender differences in off-ice variables were reduced or disappeared when values were related to LBM, indicating a similar capacity of producing strength and aerobic power in female and male hockey players. Skating performance in female hockey players may be improved by increasing thigh muscle strength, oxygen uptake, and relative muscle mass.

  • 72.
    Grigoriadis, Anastasios
    et al.
    Karolinska Institutet.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Trulsson, Mats
    Karolinska Institutet.
    Adaptability of mastication in people with implant-supported bridges2011In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 38, no 4, p. 395-404Article in journal (Refereed)
    Abstract [en]

    Objectives: We aimed to determine whether people with implant-supported bridges in both jaws, thus lacking periodontal receptors, adjust jaw muscle activity to food hardness during mastication.

    Materials and Methods: Thirteen participants with implant-supported bridges in both jaws and 13 with natural dentition chewed and swallowed soft and hard gelatine-based model foods, while electromyographic (EMG) activity of the masseter and temporal muscles was recorded bilaterally together with the position of the mandible. Data were compared by using a mixed-design anova model and a P-value<0.05 was considered statistically significant.

    Results: The number of chewing cycles and the duration of the masticatory sequence increased with food hardness in both groups, whereas vertical and lateral amplitude of the jaw movements, and the jaw-opening velocity, increased significantly with food hardness only for the dentate group. Although both groups adapted the EMG activity to the hardness of the food, the implant participants showed a significantly weaker increase in EMG activity with increased food hardness early during the masticatory sequence than the dentate participants did. In addition, the implant group showed significantly less reduction of muscle activity during the progression of the masticatory sequence than the dentate group.

    Conclusions: People with implant-supported bridges show an impaired adaptation of the muscle activity to food hardness during mastication. We suggest that a lack of sensory signals from periodontal mechanoreceptors accounts for the impairment.

  • 73.
    Grip, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Sundelin, Gunnevi
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Gerdle, Björn
    Karlsson, J Stefan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Variations in the axis of motion during head repositioning: a comparison of subjects with whiplash-associated disorders or non-specific neck pain and healthy controls2007In: Clinical Biomechanics, ISSN 0268-0033, E-ISSN 1879-1271, Vol. 22, no 8, p. 865-873Article in journal (Refereed)
  • 74.
    Grip, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Öhberg, Fredrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Sterner, Ylva
    Karlsson, J Stefan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Gerdle, Björn
    Classification of neck movement patterns related to whiplash-associated disorders using neural networks2003In: IEEE transactions on information technology in biomedicine, ISSN 1089-7771, Vol. 7, no 4, p. 412-418Article in journal (Refereed)
    Abstract [en]

    This paper presents a new method for classification of neck movement patterns related to Whiplash-associated disorders (WAD) using a resilient backpropagation neural network (BPNN). WAD are a common diagnosis after neck trauma, typically caused by rear-end car accidents. Since physical injuries seldom are found with present imaging techniques, the diagnosis can be difficult to make. The active range of the neck is often visually inspected in patients with neck pain, but this is a subjective measure, and a more objective decision support system, that gives a reliable and more detailed analysis of neck movement pattern, is needed. The objective of this study was to evaluate the predictive ability of a BPNN, using neck movement variables as input. Three-dimensional (3-D) neck movement data from 59 subjects with WAD and 56 control subjects were collected with a ProReflex system. Rotation angle and angle velocity were calculated using the instantaneous helical axis method and motion variables were extracted. A principal component analysis was performed in order to reduce data and improve the BPNN performance. BPNNs with six hidden nodes had a predictivity of 0.89, a sensitivity of 0.90 and a specificity of 0.88, which are very promising results. This shows that neck movement analysis combined with a neural network could build the basis of a decision support system for classifying suspected WAD, even though further evaluation of the method is needed.

  • 75.
    Grönlund, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Holtermann, A
    Roeleveld, K
    Karlsson, J Stefan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Quantification of motor unit synchronization from surface EMG signals with minimized dependency on muscle fibre conduction velocityManuscript (preprint) (Other academic)
  • 76.
    Grönlund, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Roeleveld, Karin
    Holtermann, Andreas
    Karlsson, J Stefan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    On-line signal quality estimation of multichannel surface electromyograms2005In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 43, no 3, p. 357-364Article in journal (Refereed)
  • 77.
    Grönlund, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Östlund, Nils
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Roeleveld, Karin
    Karlsson, J Stefan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Simultaneous estimation of muscle fibre conduction velocity and muscle fibre orientation using 2D multichannel surface electromyogram2005In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 43, no 1, p. 63-70Article in journal (Refereed)
  • 78.
    Gunnarsson, Ulf
    Department of Physiology, Karolinska Institute, Stockholm, Sweden.
    Intracerebroventricular ANP(1-28) has no obvious effects on renal blood flow and function in conscious sheep.1994In: Clinical and experimental pharmacology & physiology, ISSN 0305-1870, E-ISSN 1440-1681, Vol. 21, no 3, p. 189-94Article in journal (Refereed)
    Abstract [en]

    1. The study examines whether intracerebroventricular (ICV) infusion of atrial natriuretic peptide (human ANP,1-28) influences renal electrolyte and water excretion, vasopressin release, renal and femoral blood flows in conscious ewes. The blood flow was measured by chronically implanted ultrasonic flow probes. 2. ICV infusion of ANP(1-28) at 25 pmol/min for 60 min did not affect renal Na and K excretion or plasma vasopressin levels. In two out of six animals a mild water diuresis developed at about 50 min post-infusion. 3. The plasma osmolality, Na, K and protein concentrations did not change during the experiments. 4. The renal and femoral arterial blood flows were not influenced by 30 min ICV infusions of ANP(1-28) at 25 and 85 pmol/min. 5. It is concluded that human ANP(1-28) has no, or negligible, effects on renal function, femoral and renal blood flow when given ICV in amounts obviously elevating cerebrospinal fluid levels far above normal.

  • 79.
    Gunnarsson, Ulf
    et al.
    Department of Physiology, Karolinska Institute, Stockholm, Sweden.
    Rundgren, M
    Inefficiency of intracerebroventricular ANP to alter haemodynamic, plasma vasopressin and renin responses to haemorrhage in sheep.1994In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 150, no 4, p. 441-7Article in journal (Refereed)
    Abstract [en]

    Whether intracerebroventricular (i.c.v.) infusion of atrial natriuretic peptide (human-ANP, 1-28) 25 pmol min-1 influences the tolerance to blood loss and haemorrhage induced cardiovascular, vasopressin and renin responses were studied in five conscious sheep. The i.c.v. infusion was started 60 min prior to a slow (0.7 ml kg-1 min-1) venous haemorrhage, was run concurrently with bleeding, and for 90 min thereafter. Venous blood was removed until the mean systemic arterial pressure suddenly fell to about 50 mmHg. There were no statistically significant differences in either the bleeding volume necessary to induce the sudden decrease in blood pressure, or in cardiovascular parameters measured by venous heart thermodilution catheterization, compared with control experiments with i.c.v. infusion of artificial CSF. The plasma protein and vasopressin concentrations and renin activity were unaffected by the i.c.v. infusion of ANP as were the changes in these parameters occurring during the subsequent haemorrhage. The same negative findings were obtained with a three times higher dose of ANP(1-28) (75 pmol min-1), tested in three of the animals. Thus the i.c.v. infusion of ANP(1-28), in amounts expected to elevate the CSF concentration far above basal levels does apparently not influence normal blood pressure regulation or alter haemodynamic, vasopressin and renin responses to haemorrhage in conscious sheep.

  • 80.
    Gustafsson, Dan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    A model for investigating microcircuit changes underlying functional recovery after brain lesion in vivo2016Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
  • 81.
    Gåfvels, Mats
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Blood flow and metabolism in the corpus luteum of the rat: in vivo and in vitro studies on the ovarian luteal and follicular compartment of the rat1987Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The ovary undergoes cyclic changes in follicular growth and luteogenesis due to the action of gonadotropins and steroids. The ovary and especially the corpus luteum has an exteremely high blood flow. There is a gap in our knowledge about the physiological role of the high blood flow of the corpus luteum.

    The production of lactate, progesterone and cyclic AMP of follicles and corpora lutea incubated in vitro was analyzed and related to the tissue content of ATP to elucidate possible connections between oxygen and substrate levels and energy consumption, steroid output and LH responsiveness in vitro. It was also considered of interest to investigate if the oxygen tensions needed for ATP and progesterone production of the follicle and the corpus luteum differed. A corpus luteum model using adult pseudopregnant rats was developed and characterized according to criteria for identification of corpora lutea as well as levels of plasma steroids and gonadotropins. In vitro progesterone production was compared to plasma progesterone levels. The absolute blood flow of corpora lutea of different ages and the response to injection of hCG, noradrenaline and antidiuretic hormone was investigated with the microsphere technique. Relative blood flow changes of follicles and corpora lutea during follicular growth and luteogenesis in vivo were studied by injecting radiolabelled microspheres to anaesthetized immature rats at different time periods after injection of an ovulatory dose of pregnant mare serum gonadotropin. This approach was chosen to investigate the possible relation between follicular/luteal blood flow, steroid output and morphology in relation to the endogenous gonadotropin surge, ovulation and luteogenesis.

    Hormonal stimulation by injection of hCG and noradrenaline increased total ovarian blood flow but no evidence was found for a parallelism between luteotropism and blood flow. The increasing effect of hCG on ovarian blood flow was partly due to a shunting of blood from the uterus towards the ovary. The antidiuretic hormone potently decreased ovarian and uterine blood flow by 80-90% while blood flow of some other organs (e.g. kidney and spleen) were hardly affected. The corpus luteum of pseudopregnancy was found to produce 15“ 20 times more progesterone in vitro as compared to the preovulatory follicle. The steroidogenesis and energy production of corpora lutea was found to be more sensitive to decreases in oxygen tension in terms of tissue ATP levels and LH responsiveness of progesterone production while the follicle could compensate by increasing glycolysis. A parallelism between follicular/luteal blood flow and progesterone production in vivo was found. It was shown that the formation, growth and progesterone production of the corpus luteum was accompanied by an increase in blood flow as well as vascularization as seen under the light microscope. The endogenous gonadotropin surge did not change follicular blood flow due to the development of a follicular oedema. We hypothesize that the corpus luteum function in vivo and in vitro is dependent on higher energy levels than the preovulatory follicle and that the transformation of the follicle to a corpus luteum is supported by a high nutritive blood flow possibly to support a high demand for energy-rich substrates.

  • 82.
    Haage, David
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Laboratory of Ionic Channels of Cell Membranes, Institute of Cytology, Russian Academy of Sciences, Russia.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Allopregnanolone modulates spontaneous GABA release via presynaptic Cl- permeability in rat preoptic nerve terminals2002In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 958, no 2, p. 405-413Article in journal (Refereed)
    Abstract [en]

    The endogenous neurosteroid 3alpha-hydroxy-5alpha-pregnane-20-one (allopregnanolone) affects presynaptic nerve terminals and thereby increases the frequency of spontaneous GABA release. The present study aimed at clarifying the mechanisms underlying this presynaptic neurosteroid action, by recording the frequency of spontaneous GABA-mediated inhibitory postsynaptic currents (sIPSCs) in neurons from the medial preoptic nucleus (MPN) of rat. Acutely dissociated neurons with functional adhering nerve terminals were studied by perforated-patch recording under voltage-clamp conditions. It was shown that the sIPSC frequency increased with the external K(+) concentration ([K(+)](o)). Further, the effect of allopregnanolone on the sIPSC frequency was strongly dependent on [K(+)](o). In a [K(+)](o) of 5 mM, 2.0 microM allopregnanolone caused a clear increase in sIPSC frequency. However, the effect declined rapidly with increased [K(+)](o) and at high [K(+)](o) allopregnanolone reduced the sIPSC frequency. The effect of allopregnanolone was also strongly dependent on the external Cl(-) concentration ([Cl(-)](o)). In a reduced [Cl(-)](o) (40 mM, but with a standard [K(+)](o) of 5 mM), the effect on sIPSC frequency was larger than that in the standard [Cl(-)](o) of 146 mM. The dependence of the effect of allopregnanolone on [K(+)](o) and on estimated presynaptic membrane potential was also altered by the reduction in [Cl(-)](o). As in standard [Cl(-)](o), the effect in low [Cl(-)](o) declined when [K(+)](o) was raised, but reversed at a higher [K(+)](o). The GABA(A) receptor agonist muscimol also potentiated the sIPSC frequency. Altogether, the results suggest that allopregnanolone exerts its presynaptic effect by increasing the presynaptic Cl(-) permeability, most likely via GABA(A) receptors.

  • 83. Habib, Reza
    et al.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Neural Correlates of Availability and Accessibility in Memory2008In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 8, no 7, p. 1720-1726Article in journal (Other academic)
    Abstract [en]

    Failure to remember can be due to not having information available in memory or to an inability to access information that is available. We used functional magnetic resonance imaging to examine brain responses during encoding and successive cued recall and associative recognition tests of paired associates. Items were classified into 3 categories based on performance on the 2 retrieval tests: 1) successfully remembered (both recalled and recognized), 2) inaccessible (not recalled but later recognized), and 3) forgotten (neither recalled nor recognized). During cued recall, availability in memory was signaled in a network of regions including bilateral medial temporal lobe, left middle temporal cortex, and the parietal cortex. Memory access resulted in heightened activity in these regions as well as in left inferior frontal cortex. Encoding-related activity in hippocampus and inferior temporal cortex predicted subsequent availability and left inferior frontal activity predicted subsequent access. These results suggest that failure to access information that is available in memory may reflect weaker memory representations.

  • 84.
    Hadrévi, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Ghafouri, Bijar
    Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University and Pain and Rehabilitation Centre, County Council of Östergötland, SE 581 85 Linköping, Sweden.
    Larsson, Britt
    Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University.
    Gerdle, Björn
    Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University.
    Hellström, Fredrik
    Centre for Musculoskeletal Research, Department of Occupational and Public Health Sciences, Faculty of Health and Occupational Studies , University of Gävle, Umeå, Sweden.
    Multivariate Modeling of Proteins Related to Trapezius Myalgia, a Comparative Study of Female Cleaners with or without Pain2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9, p. e73285-Article in journal (Refereed)
    Abstract [en]

    The prevalence of chronic trapezius myalgia is high in women with high exposure to awkward working positions, repetitive movements and movements with high precision demands. The mechanisms behind chronic trapezius myalgia are not fully understood. The purpose of this study was to explore the differences in protein content between healthy and myalgic trapezius muscle using proteomics. Muscle biopsies from 12 female cleaners with work-related trapezius myalgia and 12 pain free female cleaners were obtained from the descending part of the trapezius. Proteins were separated with two-dimensional differential gel electrophoresis (2D-DIGE) and selected proteins were identified with mass spectrometry. In order to discriminate the two groups, quantified proteins were fitted to a multivariate analysis: partial least square discriminate analysis. The model separated 28 unique proteins which were related to glycolysis, the tricaboxylic acid cycle, to the contractile apparatus, the cytoskeleton and to acute response proteins. The results suggest altered metabolism, a higher abundance of proteins related to inflammation in myalgic cleaners compared to healthy, and a possible alteration of the contractile apparatus. This explorative proteomic screening of proteins related to chronic pain in the trapezius muscle provides new important aspects of the pathophysiology behind chronic trapezius myalgia.

  • 85.
    Hagström, Linn
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Karp, Kjell
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Impact of age and sex on normal left heart structure and function2017In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 37, no 6, p. 759-766Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Accurate age- and sex-related normal reference values of ventricular structure and function are important to determine the level of dysfunction in patients. The aim of this study therefore was to document normal age range sex-related measurements of LV structural and functional measurements to serve such purpose.

    METHODS: We evaluated left ventricular structure and function in 293 healthy subjects between 20 and 90 years with equally distributed gender. Doppler echocardiography was used including measure of both systolic and diastolic functions.

    RESULTS: Due to systolic LV function, only long axis function correlated with age (r = 0·55, P<0·01) and the correlation was stronger in females. Concerning diastolic function, there was a strong age correlation in all parameters used (r = 0·40-0·74, P<0·001). Due to LV structural changes over age, females showed a larger reduction in end-diastolic volumes, but no or trivial difference in wall thickness after the age of 60 years.

    CONCLUSION: Age is associated with significant normal changes in left ventricular structure and function, which should be considered when deciding on normality. These changes are related to systemic arterial changes as well as body stature, thus reflecting overall body ageing process. Furthermore, normal cardiac ageing in females might partly explain the higher prevalence of heart failure with preserved ejection in females.

  • 86. Hamberg, Jern
    et al.
    Björklund, Martin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Nordgren, Bengt
    Sahlstedt, Bo
    Stretchability of the rectus femoris muscle: investigation of validity and intratester reliability of two methods including x-ray analysis of pelvic tilt.1993In: Archives of Physical Medicine and Rehabilitation, ISSN 0003-9993, E-ISSN 1532-821X, Vol. 74, no 3, p. 263-270Article in journal (Refereed)
    Abstract [en]

    Validity and intratester reliability of two test methods designed to identify stretchability of the rectus femoris muscle (RFM) was investigated, combined with x-ray analysis of pelvic tilt in the sagittal plane. The first method is commonly used in clinical practice. The second is a new technique supposed to tilt the pelvis posteriorly and thus further separate the origin and insertion of the muscle. Investigation of validity and intratester reliability of the two methods was made by testing and retesting a random sample of 71 persons. The tests were performed with an equipment that automatically recorded the angle of knee flexion from a previously determined applied torque, indicating the end point of motion for that particular subject. Angle of knee flexion and subjective estimation of pain sensation due to stretch were recorded at each measurement. The pelvic tilt-analysis consisted of test-retest reliability of x-ray measurements, comparison between the methods in both starting and final position, and x-ray and electronic goniometer measurements. All applied torques were measured with a strain gauge. Two out of three criteria of validity favored the new method and the third pointed out the two methods as equal. The two methods as well as the x-ray measurements showed high reliability, and the hypothesis of a more posterior tilted pelvis in the new method was confirmed. The electronic goniometer was less sensitive than x-ray, but proposed to analyse pelvic tilt clinically. Methodology procedures for joint angle measurements are discussed.

  • 87.
    Hansson Mild, Kjell
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Biophysical aspects of permeation and diffusion of water in frog eggs1974Doctoral thesis, comprehensive summary (Other academic)
  • 88.
    Hao, Manzhao
    et al.
    Institute of Rehabilitation Engineering, Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
    He, Xin
    Institute of Rehabilitation Engineering, Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
    Xiao, Qin
    Institute of Rehabilitation Engineering, Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
    Alstermark, Bror
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Lan, Ning
    Institute of Rehabilitation Engineering, Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
    Corticomuscular transmission of tremor signals by propriospinal neurons in Parkinson's disease.2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, article id e79829Article in journal (Refereed)
    Abstract [en]

    Cortical oscillatory signals of single and double tremor frequencies act together to cause tremor in the peripheral limbs of patients with Parkinson's disease (PD). But the corticospinal pathway that transmits the tremor signals has not been clarified, and how alternating bursts of antagonistic muscle activations are generated from the cortical oscillatory signals is not well understood. This paper investigates the plausible role of propriospinal neurons (PN) in C3-C4 in transmitting the cortical oscillatory signals to peripheral muscles. Kinematics data and surface electromyogram (EMG) of tremor in forearm were collected from PD patients. A PN network model was constructed based on known neurophysiological connections of PN. The cortical efferent signal of double tremor frequencies were integrated at the PN network, whose outputs drove the muscles of a virtual arm (VA) model to simulate tremor behaviors. The cortical efferent signal of single tremor frequency actuated muscle spindles. By comparing tremor data of PD patients and the results of model simulation, we examined two hypotheses regarding the corticospinal transmission of oscillatory signals in Parkinsonian tremor. Hypothesis I stated that the oscillatory cortical signals were transmitted via the mono-synaptic corticospinal pathways bypassing the PN network. The alternative hypothesis II stated that they were transmitted by way of PN multi-synaptic corticospinal pathway. Simulations indicated that without the PN network, the alternating burst patterns of antagonistic muscle EMGs could not be reliably generated, rejecting the first hypothesis. However, with the PN network, the alternating burst patterns of antagonist EMGs were naturally reproduced under all conditions of cortical oscillations. The results suggest that cortical commands of single and double tremor frequencies are further processed at PN to compute the alternating burst patterns in flexor and extensor muscles, and the neuromuscular dynamics demonstrated a frequency dependent damping on tremor, which may prevent tremor above 8 Hz to occur.

  • 89.
    Hedlund, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Sojka, Peter
    Department of Health Sciences, Mid-Sweden University, Östersund, Sweden.
    Lundström, Ronnie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lindström, Britta
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Torque-angle relationship are better preserved during eccentric compared to concentric contractions in patients with stroke2012In: Isokinetics and exercise science, ISSN 0959-3020, E-ISSN 1878-5913, Vol. 20, no 2, p. 129-140Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare the effect of isokinetic contraction mode and velocity on the torque-angle relationship during maximum voluntary elbow flexion in patients with stroke, age-matched healthy subjects and young subjects. To eliminate the effect of torque amplitude differences between subjects and groups, the torque values throughout the ROM were individually normalized to the peak value for each contraction velocity. The results show that in stroke patients the normalized torque angle relationship during the eccentric contractions was better preserved than during concentric contractions. Specifically, during eccentric contractions, stroke patients exhibited a torque-angle relationship that was closer to normal as the test velocity increased. The opposite trend could be seen in concentric contractions where the torque-angle relationship became more divergent from normal with a rise in the velocity. The torque-angle relationships were essentially the same for the control groups, irrespective of contraction mode or velocity. These findings may have significance for loading patterns of resistance training exercises used with stroke patients as such exercises normally are biomechanically designed for normal torque angle relationships. In clinical practice, these findings may partly explain why the strength increases due to resistance training are limited for patients with stroke.   

  • 90.
    Heijbel, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neurophysiology.
    Benign epilepsy of children with centro-temporal EEG foci: clinical, genetic and neurophysiological studies1976Doctoral thesis, comprehensive summary (Other academic)
  • 91.
    Hellström, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ericsson, Madelene
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Faraz, Mahmood
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Anderson, Fredrick
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Center Stockholm/Gotland, Stockholm, Sweden.
    Nilsson, Stefan K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Cardiac hypertrophy and decreased high-density lipoprotein cholesterol in Lrig3-deficient mice2016In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 310, no 11, p. R1045-R1052Article in journal (Refereed)
    Abstract [en]

    Genetic factors confer risk for cardiovascular disease. Recently, large genome-wide population studies have shown associations between genomic loci close to LRIG3 and heart failure and plasma high-density lipoprotein (HDL) cholesterol level. Here, we ablated Lrig3 in mice and investigated the importance of Lrig3 for heart function and plasma lipid levels. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze Lrig3 expression in the hearts of wild-type and Lrig3-deficient mice. In addition, molecular, physiological, and functional parameters such as organ weights, heart rate, blood pressure, heart structure and function, gene expression in the heart, and plasma insulin, glucose, and lipid levels were evaluated. The Lrig3-deficient mice were smaller than the wild-type mice but otherwise appeared grossly normal. Lrig3 was expressed at detectable but relatively low levels in adult mouse hearts. At 9 mo of age, ad libitum-fed Lrig3-deficient mice had lower insulin levels than wildtype mice. At 12 mo of age, Lrig3-deficient mice exhibited increased blood pressure, and the Lrig3-deficient female mice displayed signs of cardiac hypertrophy as assessed by echocardiography, heart-to-body weight ratio, and expression of the cardiac hypertrophy marker gene Nppa. Additionally, Lrig3-deficient mice had reduced plasma HDL cholesterol and free glycerol. These findings in mice complement the human epidemiological results and suggest that Lrig3 may influence heart function and plasma lipid levels in mice and humans.

  • 92.
    Henriksson, Tommy
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine. Umeå University, Faculty of Social Sciences, Umeå Centre for Gender Studies (UCGS).
    Physiological- and Socio-Cultural Conditions for Performance in Women's Ice Hockey2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: The ice hockey community is founded on masculine norms and values, and the hockey rink is often described as “the home of men’s ice hockey”. Despite a growing popularity, women’s ice hockey has low priority in comparison to the men’s game. On top of that, the women’s game does not allow body checking, which makes it deviant from what some see as “the real game of ice hockey”. The checking prohibition causes physiological requirements to differ from the men’s game, and since women are underrepresented in ice hockey research, not much is known regarding the physiological- and socio-cultural conditions of women’s ice hockey. The overall aim of this doctoral thesis is to investigate physiological- and socio-cultural conditions important for performance in women’s ice hockey.

    Methods: This thesis is unique in terms of the interdisciplinary approach between physiology and gender science, and the inclusion of studies based on both qualitative and quantitative research methods. Qualitative thematic interviews with ice hockey coaches from Sweden, Canada, and the United States were used to explore socio-cultural conditions in relation to performance and sport development (Paper I). Relative age effect (RAE) in relation to maturity status was examined through anthropometric measurements and a player questionnaire (Paper II). Physiological field- and laboratory assessments were used to investigate physiological conditions and performance in female competitive ice hockey players from Sweden (Paper III-IV), and players from Canada (Paper IV).

    Results: The findings from Paper I suggest that coaches need to maintain a holistic approach to coaching to be able to coordinate and optimize the effects based on available conditions. Socio-cultural conditions, such as structural and financial support, are mentioned as important to support opportunities in women’s ice hockey. Furthermore, the results (Paper I) show that female players in Canada and the United States have superior opportunities compared to female players in Sweden. These advantages are mainly attributed to the support provided by the North American education systems. The findings from Paper II suggest that the relative age effect (RAEs) in women’s hockey are also influenced by socio-cultural conditions. Significant RAE (p<.05) was found for Swedish players born in the third quartile (Q3) and for Canadian player born in the second quartile (Q2). Players born in the fourth quartile (Q4) are significantly (p<.05) underrepresentated in both countries. Players tend to be average or late maturers, but no differences can be found by country or position. The findings from Paper III show that field-based assessments are comparable to laboratory assessments with the purpose of predicting skating performance. The Prediction models accounted for 13.6 % to 42 % (laboratory-based models) and 24.4 to 66.3 % (field-based models) of the variance in skating time. Regardless of assessment method, uni-lateral assessments are superior to bi-lateral assessments. The results support the use of field-based assessments in Paper IV. The findings from Paper IV show various physiological profiles for female Swedish and Canadian players. Swedish players had less body fat (p=.007), more lean mass (p=.005), and greater aerobic fitness measured with the20-meter shuttle run beep test (p=<.001). Canadian players had greater maximal isometric leg strength (p=.026), exhibit a greater running acceleration (p=<.001), performed better in single leg standing long jumps (right leg p=.002, left leg p=.030), and showed better anaerobic endurance (p=.029) on- ice. No significant differences can be found between forwards and defenders.

    Conclusion: The findings of this study show that physiological- and socio-cultural conditions should both be considered in relation to performance in women’s ice hockey. For example, the various physiological profiles are probably an effect of the different socio-cultural conditions in Sweden and Canada. The Canadian profile may be better adapted to performance in ice hockey, but further research is needed to establish a relationship. Since women’s ice hockey often has somewhat limited resources, this knowledge may help optimize the effect of the available resources, and thus improve performance. Improved performance may have a positive long-term effect on the symbolic view of women’s ice hockey. Women can probably further optimize their physical performance in relation to their current conditions. But for permanent changes to occur, power structures in sport must also change. Women themselves have limited opportunities to affect the dominating gender norms and values in ice hockey.

  • 93.
    Henriksson, Tommy
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine. The National Graduate School of Gender Studies.
    Fjellman-Wiklund, Anncristine
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Gilenstam, Kajsa
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine.
    Running a team is like laying a puzzle: Elite coaches' perspective on women's ice hockey2013Conference paper (Refereed)
  • 94.
    Henriksson, Tommy
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Vescovi, Jason D.
    Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, ON, Canada..
    Geithner, Christina A.
    Department of Organizational Leadership, Gonzaga University.
    Fjellman-Wiklund, Anncristine
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Gilenstam, Kajsa
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Performance profiling of female ice hockey players by country and positionManuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: The purposes of this study were to determine whether physiological qualities and on- ice skating performance differ by country and by position in women’s ice hockey.

    Design: Cross-sectional study.

    Methods: A total of 109 female ice hockey players volunteered for the study: 45 players from Sweden (19.38 ± 2.56 years; body mass 69.43 ± 7.05 kg: height 169.83 ± 5.03 cm) and 64 players from Canada (19.84 ± 1.62 years; body mass 68.28 ± 7.72 kg: height 166.14 ± 13.67 cm). Anthropometric assessments included estimated body composition using skinfold measurements. Physiological assessments included tests for acceleration, strength, power and aerobic endurance. Performance assessments included on-ice agility and anaerobic tests. Data were analyzed for mean differences by country and position using a two-way ANOVA.

    Results: The Swedish players had less body fat (p=.007), more lean mass (p=.005), and higher Beep test scores (p=.001). The Canadian players performed better on leg strength (p=.026), acceleration (p=.001), single leg standing long jumps (right leg p=.002, left leg p=.030) and the modified repeat sprint skate (MRSS) (p=.029). Positional comparisons between forwards (F) and defenders (D) showed no significant differences. F and D performed better than goalies (G) on the beep test (p=.002 and p=.002, respectively).

    Conclusion: The findings showed that the physiological profile for the female ice hockey players in this sample differed by country. The results indicate that the Canadian profile may be better adapted for on-ice performance. No performance differences were found between F and D. G are subjected to completely different requirements, due to variation in equipment and movement patterns, and should not be compared to F and D.

  • 95.
    Hilgert Elcadi, Guilherme
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine.
    Near infrared spectroscopy for assessing oxygenation and hemodynamics in the upper extremities of healthy subjects and patients with work-related muscle pain2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The prevalence of work-related muscle pain (WRMP) is large in the general population in the industrialized world. Despite significant advances over recent years in some research areas, the mechanisms of why WRMP occurs and the pathophysiological mechanisms behind the disorders are still unclear. One suggested explanation is that WRMP is caused initially by a limitation of the local muscle circulation and oxidative metabolism. There is a lack of objective methods to gauge the development and diagnosis of WRMP.

    Near infrared spectroscopy (NIRS) is a non-invasive technique that allows for determinations of oxygenation and blood flow. The purpose of this thesis was to evaluate NIRS (1) as a method for measuring muscle oxygenation and hemodynamics for the extensor carpi radialis (ECR) and trapezius descendens muscles (TD), and (2) to investigate whether variables measured by NIRS differed between patients diagnosed with WRMP and healthy subjects.

    Several variables of NIRS were produced and investigated. These included muscle oxygenation (StO2%), changes during contractions (ΔStO2%) and StO2% recovery (Rslope), total hemoglobin (HbT) as an indication of blood volume and its changes during contractions (ΔHbT). In addition, for the ECR, by applying an upper arm venous occlusion (VO) HbTslope increase as a surrogate of blood flow, and for both VO and arterial occlusion (AO) HHbslope increase (i.e. deoxyhemoglobin slope) as a surrogate of oxygen consumption were variables of interest.

    A first objective was to determine how StO2% and HbT responded to various contraction forces and how it related to muscle activation measured by electromyography (EMG). For both muscles isometric contractions of 10, 30, 50 and 70% of maximal voluntary contraction (MVC) were maintained for 20 s each by healthy males and females; additionally a 10% MVC contraction was sustained for 5 min. For the different contraction levels, predictable relationships were seen between ΔStO2% and force, and between ΔStO2% and EMG RMS amplitude. The general trend was a decrease in ΔStO2% with increasing force and increasing EMG. Females showed a tendency for a higher oxygen use (i.e., drop in StO2%) for the ECR over force levels than males and a higher RMS% MVC for the TD. For the 10% MVC contraction sustained for 5 min gender specific changes over time for HbT and RMS for the ECR, and for StO2% for the TD muscle were seen.

    A second objective was to determine the day-to-day reliability of NIRS variables for the ECR and TD muscles at group level (Pooled data) and at gender level (males and females). Measurements were performed on two occasions separated by 4-6 days and intraclass correlation coefficients (ICC) and limits of agreement (LOA) were determined as reliability and reproducibility indicators, respectively. Variables tested were ΔStO2% during submaximal isometric contractions of 10, 30, 50 and 70% MVC and StO2% recovery (Rslope) after contractions and after AO. For the ECR, HbTslope as an indication of blood flow (using VO) and HHbslope as a surrogate of oxygen consumption for both VO and AO were computed. For ΔStO2% for the ECR the highest ICC was at 30% MVC for both the pooled data and at gender level. For the TD ICCs were comparably high for 30, 50, 70 % MVC (for both muscles the ΔStO2% at 10% MVC showed the lowest ICC). Further, females showed a higher ICC than males for contraction levels of 50 and 70% MVC. For both muscles, LOA for ΔStO2% was lowest at 10% and highest at 50 and 70% MVC. For the ECR Rslope ICCs were high for all contraction levels, but was lower for AO; LOA was lowest at 70% MVC. For the TD, Rslope ICCs were also high for all contraction levels and LOA was lowest at 30 % MVC. ICC for HbTslope was the lowest of all variables tested. For HHbslope ICC was higher for AO than for VO, and LOA was lower for AO.

    A third objective was to determine if there were differences between healthy subjects and patients diagnosed with WRMP in ΔStO2% and ΔHbT responses during varying submaximal contractions (10, 30, 50 and 70% MVC), and StO2% recovery (Rslope) immediately after contractions and AO. Additional variables tested in the ECR at rest were HHbslope to indicate oxygen consumption (using AO) and HbTslope as an indication of blood flow. There were no differences between groups in ΔStO2% and ΔHbT variables during the contractions or Rslope in the recovery after contractions or AO. Furthermore, HbTslope was not different between groups However, oxygen consumption for the ECR and StO2% for the TD at rest were significantly greater for healthy subjects compared to patients.

    A fourth objective was to determine if there were differences in StO2% and HbT between healthy subjects and WRMP patients during a 12 min sustained contraction of 15 % MVC. In addition, the protocol included a recovery period of 30 min. Prior to contraction, as well as during the recovery period, HbTslope as a surrogate of blood flow was determined for the ECR. Neither the ECR nor the TD exhibited significant differences between groups for StO2% and HbT during the contraction. For the TD patients showed a lower StO2% value at rest and throughout the contraction than healthy subjects. For the ECR HbT during the sustained contraction the general trend was an initial decrease with gradual increase throughout the contraction for both groups. For HbTslope no differences were seen between patients and healthy subjects before the sustained contraction and during the recovery period for both muscles.

    NIRS is deemed a suitable technique for assessing physiological measurements of the upper extremity, including for day-to-day testing.

    NIRS was not able to distinguish between the patients with WRMP and controls. A concern in the thesis is the characteristics of the patient group in being equally active in recreational sports, actively working, and similar in muscle strength as controls. Thus, applying NIRS for studying a more severe patient group could yield different results.

  • 96.
    Holmberg, Ellinor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Allopregnanolone effects on food intake and weight gain2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Obesity is currently one of the major causes of ill health and it is clear that overeatingis the cause of obesity. However, the actions of many endogenous factors that contribute to overeating are still not well understood. Gamma-aminobutyric acid (GABA)-ergic transmission has been shown to be of great importance for food intake regulation. The progesterone metabolite allopregnanolone is a potent positive GABAA receptor modulating steroid (GAMS) and in humans, elevated allopregnanolone levels have been suggested to be involved in increased food intake, and also with overweight and obesity. GABAA receptors that express the α2 and α3 subunits are proposed to be the main subtypes involved in food intake regulation. Therefore, the aims of the work in this thesis were to further investigate the effect of allopregnanolone on food intake, feeding behaviour, possible effects on weight gain and also to characterize a possible antagonist at α2β3γ2and α3β3γ2 GABAA receptors.

    Methods Allopregnanolone effects on food intake of different food items were recorded in male Wistar rats. Feeding patterns were analyzed. Food preference tests were also conducted and rats were repeatedly exposed to allopregnanolone under different feeding conditions to elucidate possible effects on body weight gain. To deeper investigate GABAA receptor subtypes suggested to be involved in food intake regulation, electrophysiological whole-cell patch-clamp recordings were performed to identify the specificity of the GAMS antagonist UC1020, at human α2β3γ2 and α3β3γ2 GABAA receptors expressed in HEK293-cells.

    Results Allopregnanolone increased the intake of standard chow, cookies and a high fat diet in male Wistar rats. Preferentially, allopregnanolone increased the rats´intake of the more calorie dense food type. Allopregnanolone reduced feeding latency and prolonged feeding duration. The increased chow intake induced by allopregnanolone was more pronounced at the beginning of the rats´ active period compared to the inactive. Repeated allopregnanolone administration during 5 consecutive days led to an increased body weight gain, more evident in schedule fed rats on a high fat diet. Both obesity prone and obesity resistant rats gained significantly more weight with repeated allopregnanolone exposure and the increased body weight gain correlated with increased food intake. The compound UC1020 was a potent antagonist of GAMS-enhanced GABA evoked currents at human α3β3γ2 GABAA receptors, whereas it had no effect at α2β3γ2 GABAA receptors.

    Conclusions Our findings indicate that allopregnanolone induced hyperphagia may be one of the endogenous factors involved in weight gain, especially when the diet is energy-rich. The compound UC1020 may prove useful for investigating the involvement of the α2 and α3 GABAA receptor subtypes in GAMS-induced hyperphagia.

  • 97.
    Holmberg, Ellinor
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Johansson, Maja
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Haage, David
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Allopregnanolone preferentially induces energy-rich food intake in male Wistar rats2014In: Physiological Reports, E-ISSN 2051-817X, Vol. 2, no 12, p. e12190-Article in journal (Refereed)
    Abstract [en]

    Obesity is an increasing problem and identification of the driving forces for overeating of energy-rich food is important. Previous studies show that the stress and sex steroid allopregnanolone has a hyperphagic effect on both bland food and palatable food. If allopregnanolone induces a preference for more palatable or for more energy-rich food is not known. The aim of this study  was to elucidate the influence of allopregnanolone on food preference. Male Wistar rats were subjected to two different food preference tests: a choice between standard chow and cookies (which have a higher energy content and also are more palatable than chow), and a choice between a low caloric sucrose solution and standard chow (which has a higher energy content and is less palatable than sucrose). Food intake was measured for 1 h after acute subcutaneous injections of allopregnanolone. In the choice between cookies and chow allopregnanolone significantly increased only the intake of cookies.When the standard chow was the item present with the highest caloric load, the chow intake was increased and allopregnanolone had no effect on intake of the 10% sucrose solution. The increased energy intakes induced by the high allopregnanolone dose compared to vehicle were very similar in the two tests,120% increase for cookies and 150% increase for chow. It appears that in allopregnanolone-induced hyperphagia, rats choose the food with the highest energy content regardless of its palatability.

  • 98.
    Holmberg, Ellinor
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Johansson, Maja
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Löfgren, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Haage, David
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Repeated allopregnanolone exposure induces weight gain in schedule fed rats on high fat diet2015In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 140, p. 1-7Article in journal (Refereed)
    Abstract [en]

    Ingestion of energy rich high fat diets is one of the determining factors associated with the obesity epidemic. Therefore, much can be learned from studies of obesity-related substances given to animals fed a high fat diet.The progesterone metabolite allopregnanolone is a potent positive modulator of the gamma-aminobutyric acid(GABA)A-receptor, and both allopregnanolone and GABA have been implicated in evoking hyperphagia. In this study, food intake and body weight gain were investigated during repeated allopregnanolone exposure. Male Wistar rats were studied when fed chow ad libitum, with chow access for 4h per day or with 45% high fat pellets for 4 h per day. Rats on the high fat diet were separated into obesity prone and obesity resistant individuals.Subcutaneous injections of allopregnanolone were given once daily overfive consecutive days. Repeated exposure to allopregnanolone lead to increased weight gain, significantly so in schedule fed rats on a high fat diet. The increased weight gain was correlated to an increased energy intake. Both obesity resistant and obesityprone rats responded to allopregnanolone with increased weight gain. Obesity resistant rats treated with allopregnanolone increased their energy intake and ate as much as vehicle treated obesity prone rats. Their weight gain was also increased to the level of obesity prone rats injected with just the vehicle carrier oil. Thus, it appears that allopregnanolone may be one of the endogenous factors involved in weight gain, especiallywhen the diet is rich in fat.

  • 99.
    Holmlund, Petter
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Fluid dynamic principles for analysis of intracranial pressure control: application towards space medicine and hydrocephalus2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Intracranial pressure (ICP) is an important component of the fluid dynamic environment of the brain and plays a central role with regards to the maintenance of normal cerebral blood flow and neuronal function. However, many regulatory mechanisms controlling the ICP are still poorly understood. One major gap in knowledge in this regard is the mechanism behind the postural/gravitational control of ICP. This is partly due to the fact that most ICP investigations are performed with the patients in a supine or recumbent position. Since most people spend 16 hours a day in an upright position, understanding these mechanics is highly motivated. Also spurring research on this topic is the increasing number of reports of the spaceflight-associated neuro-ocular syndrome (SANS) found in astronauts after prolonged exposure to weightlessness (i.e. microgravity), where evidence suggests that a disrupted balance between ICP and intraocular pressure (IOP) may be an underlying cause. Understanding how ICP is regulated with respect to posture could therefore provide important insight into the alterations introduced by microgravity, where postural effects are removed, and how to improve the safety of astronauts who are susceptible to this syndrome. Here on earth, disturbances in the ICP or cerebrospinal fluid (CSF) dynamics are associated with the development of chronic neurological diseases. One particular disease of interest is communicating hydrocephalus, where the cerebral ventricles are enlarged despite the absence of macroscopic CSF flow obstructions. A common finding in these patients is that of altered pulsatile flow in the CSF. The overall aim of this thesis was to utilize fluid dynamic principles to describe and validate potential regulatory mechanisms behind postural changes in ICP and causes of ventriculomegaly. The thesis is based on four scientific papers (paper I—IV).

    A postural dependency of the IOP-ICP pressure difference was verified by simultaneous measurements of ICP (assessed through lumbar puncture) and IOP (measured with an Applanation Resonance Tonometer) (paper I). Based on these measurements, a 24-hour average of the IOP-ICP pressure difference at the level of the eye was estimated for the state of microgravity, predicting a reduced pressure difference in space compared with that on earth.

    A hypothesis where postural changes in ICP are described by hydrostatic effects in the venous system, and where these effects are altered by the collapse of the internal jugular veins (IJVs) in more upright positions, was evaluated (paper II and III). Using ultrasound data, it was shown that the venous hydrostatic pressure gradient was balanced by viscous pressure losses in the collapsed IJVs to uphold a near atmospheric pressure at the level of the neck in the upright posture (paper II). A full evaluation of the hypothesis was then performed, based on simultaneous assessment of ICP, central venous pressure (through a PICC-line) and venous collapse in 7 postures of upper-body tilt in healthy volunteers (paper III).The proposed description could accurately predict the general changes seen in the measured ICP for all investigated postures (mean difference: -0.03±2.7 mmHg or -4.0±360 Pa).

    Pulsatile CSF flow-induced pressure differences between the ventricles and subarachnoid space were evaluated as a source for ventriculomegaly in communicating hydrocephalus (paper IV). The pressure distributions resulting from the pulsatile CSF flow were calculated using computational fluid dynamics based on MRI data. The estimated pressures revealed a net pressure difference (mean: 0.001±0.003 mmHg or 0.2±0.4 Pa, p=0.03) between the ventricles and the subarachnoid space, over the cardiac cycle, with higher pressure in the third and lateral ventricles.

    In conclusion, the results of this thesis support venous hydrostatics and jugular venous collapse as key governing factors in the postural/gravitational control of ICP. Furthermore, a postural dependency of the IOP-ICP pressure difference was demonstrated, providing a potential explanation for how an imbalance between the pressure of the eye and brain can be introduced in microgravity. Computational fluid dynamic analysis revealed that the altered pulsations in communicating hydrocephalus generate a pressure gradient within the CSF system. However, the gradient was small and additional effects are probably needed to explain the ventriculomegaly in these patients. 

  • 100.
    Holmlund, Petter
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jugular vein collapse in upright and its relation to intracranial pressure regulation2017In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, p. 297-297Article in journal (Refereed)
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