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    Charlotte Suetta

    Key points Elderly individuals require a prolonged recovery phase in order to return to initial muscle mass levels following short‐term immobilisation. The cellular mechanisms responsible for the attenuated re‐growth and associated... more
    Key points Elderly individuals require a prolonged recovery phase in order to return to initial muscle mass levels following short‐term immobilisation. The cellular mechanisms responsible for the attenuated re‐growth and associated molecular signalling processes in ageing human skeletal muscle are not fully understood. The main study finding was the observation of a less marked muscle mass recovery after immobilisation in elderly compared to young individuals that was paralleled by an elevation in myogenic precursor cell content in young individuals only, whereas the elderly failed to demonstrate any change in myogenic precursor cells. No age‐related differences were observed in the expression of major myogenic regulating factors known to promote skeletal muscle hypertrophy or satellite cell proliferation (IGF‐1Ea, MGF, MyoD1, myogenin, HGF gene products). In contrast, the expression of myostatin demonstrated a more pronounced up‐regulation following immobilisation along with an att...
    Background The incidence of colorectal cancer (CRC) increases with age. Older patients are a heterogeneous group ranging from fit to frail with various comorbidities. Frail older patients with CRC are at increased risk of negative... more
    Background The incidence of colorectal cancer (CRC) increases with age. Older patients are a heterogeneous group ranging from fit to frail with various comorbidities. Frail older patients with CRC are at increased risk of negative outcomes and functional decline after cancer surgery compared to younger and fit older patients. Maintenance of independence after treatment is rarely investigated in clinical trials despite older patients value it as high as survival. Comprehensive geriatric assessment (CGA) is an evaluation of an older persons’ medical, psychosocial, and functional capabilities to develop an overall plan for treatment and follow-up. The beneficial effect of CGA is well documented in the fields of medicine and orthopaedic surgery, but evidence is lacking in cancer surgery. We aim to investigate the effect of CGA on physical performance in older frail patients undergoing surgery for CRC. Methods GEPOC is a single centre randomised controlled trial including older patients ...
    A validated, standardized, and feasible test to assess muscle power in older adults has recently been reported: the sit‐to‐stand (STS) muscle power test. This investigation aimed to assess the relationship between relative STS power and... more
    A validated, standardized, and feasible test to assess muscle power in older adults has recently been reported: the sit‐to‐stand (STS) muscle power test. This investigation aimed to assess the relationship between relative STS power and age and to provide normative data, cut‐off points, and minimal clinically important differences (MCID) for STS power measures in older women and men.
    Sarcopenia increases mortality in patients with end-stage liver disease. We show that arm lean mass determined by dual-energy X-ray absorptiometry is a better marker than the traditional appendicular skeletal muscle mass when predicting... more
    Sarcopenia increases mortality in patients with end-stage liver disease. We show that arm lean mass determined by dual-energy X-ray absorptiometry is a better marker than the traditional appendicular skeletal muscle mass when predicting sarcopenia-related mortality in patients with cirrhosis of different severity. The findings add to the dispute about the optimal method for repeated assessments of skeletal muscle status in patients with cirrhosis and may have implications for clinical decision making.
    Menopause is associated with increased risk of cardiovascular disease and the causal factors have been proposed to be the loss of estrogen and the subsequent alterations of the hormonal milieu. However, which factors contribute to the... more
    Menopause is associated with increased risk of cardiovascular disease and the causal factors have been proposed to be the loss of estrogen and the subsequent alterations of the hormonal milieu. However, which factors contribute to the deterioration of cardiometabolic health in postmenopausal women is debated as the menopausal transition is also associated with increased age and fat mass. Furthermore, indications of reduced cardiometabolic adaptations to exercise in postmenopausal women add to the adverse health profile. We sought to evaluate risk factors for type 2 diabetes and cardiovascular disease in late premenopausal and early postmenopausal women, matched by age and body composition, and investigate the effect of high-intensity training. A 3-month high-intensity aerobic training intervention, involving healthy, nonobese, late premenopausal (n = 40) and early postmenopausal (n = 39) women was conducted and anthropometrics, body composition, blood pressure, lipid profile, glucos...
    Single Muscle Fiber Characteristics of The Oldest-Old Gregory Grosicki, Robert Standley, Kevin Murach, Ulrika Raue, Kiril Minchev, Paul Coen, Anne Newman, Steven Cummings, Tamara Harris, Stephen Kritchevsky, Bret Goodpaster, Scott Trappe,... more
    Single Muscle Fiber Characteristics of The Oldest-Old Gregory Grosicki, Robert Standley, Kevin Murach, Ulrika Raue, Kiril Minchev, Paul Coen, Anne Newman, Steven Cummings, Tamara Harris, Stephen Kritchevsky, Bret Goodpaster, Scott Trappe, FACSM. Ball State University, Muncie, IN. Translational Research Institute for Metabolism and Diabetes, Orlando, FL. University of Pittsburgh, Pittsburgh, PA. California Pacific Medical Center Research Institute, San Francisco, CA. National Institute on Aging, Bethesda, MD. Wake Forest School of Medicine, Winston-Salem, NC. (Sponsor: Scott Trappe, FACSM) Email: gjgrosicki@gmail.com
    A decline in physical capacity takes place with increasing age that negatively affects overall physical function including work ability and the ability to perform typical activities of daily living (ADL). The overall aim of the present... more
    A decline in physical capacity takes place with increasing age that negatively affects overall physical function including work ability and the ability to perform typical activities of daily living (ADL). The overall aim of the present study was to determine the neuromuscular adaptations to long-term (1 year) football and strength training in older untrained adults, and to assess the concurrent effect on functional ADL capacity. Twenty-seven healthy elderly males (68.2 ± 3.2 years) were randomly assigned to 12 months of either recreational football training (FT: n = 10), strength training (ST: n = 9) or served as inactive controls (CON: n = 8). Recreational football training consisted of small-sided training sessions whereas strength training consisted of high intensity exercises targeting the lower extremity and upper body. Maximal thigh muscle strength and rate of force development (RFD) were assessed with isokinetic dynamometry, while postural balance and vertical jumping performance were evaluated using force plate analysis. Furthermore, functional ability was evaluated by stair-ascent and chair-rising testing. A total of nine, nine and seven participants from FT, ST and CON, respectively, were included in the analysis. Both exercise regimens led to substantial gains in functional ability, evidenced by 24 and 18 % reduced stair-ascent time, and 32 and 21 % increased chair-rising performance in FT and ST, respectively (all P < 0.05). Long-term strength training led to increased concentric (14 %; P < 0.01) and isometric (23 %; P < 0.001) quadriceps and isometric hamstring strength (44 %; P < 0.0001), whereas football training mainly resulted in enhanced hamstring strength (18 %, P < 0.05) and RFD (89 %, P < 0.0001). Long-term (1 year) strength training led to increased quadriceps and hamstring strength, whereas the adaptations to football training mainly included enhanced strength and rapid force capacity of the hamstring muscles. Gains in functional ability were observed in response to both training regimens, evidenced by reduced stair-ascent time and increased chair-rising performance. Long-term football exercise and strength training both appear to be effective interventional strategies to improve factors of importance for ADL by counteracting the age-related decline in lower limb strength and functional capacity among old male adults. This could potentially be a way to improve work ability of senior workers.
    The use of fast-track regimes has led to a marked decline in complication rates post surgery. Nevertheless, older people have an increased risk of loss of muscle mass and strength and disability post surgery compared to younger adults.... more
    The use of fast-track regimes has led to a marked decline in complication rates post surgery. Nevertheless, older people have an increased risk of loss of muscle mass and strength and disability post surgery compared to younger adults. Consequently, attempts to counteract these problems seem highly relevant. The number of studies on the effect of perioperative training is still limited. However, there is increasing evidence that strength training commenced early post surgery is safe and effective in regard to restore muscle function in older patients going through acute or elective surgery.
    Large vessel vasculitis, including giant cell arteritis and Takayasu arteritis, is traditionally diagnosed and classified according to the American College of Rheumatology criteria, which do not include findings on imaging modalities. We... more
    Large vessel vasculitis, including giant cell arteritis and Takayasu arteritis, is traditionally diagnosed and classified according to the American College of Rheumatology criteria, which do not include findings on imaging modalities. We present a case in which non-invasive imaging with 18F-fluorodeoxyglucose positron emission tomography/computed tomography gave essential information in the diagnostic work-up of large vessel vasculitis in a female presenting with non-specific symptoms. We discuss the role of nuclear medicine imaging in early diagnosis and follow-up of this inflammatory disease, characterized by granulomatous panarteritis of the aorta and its major branches.
    Trapezius myalgia - chronic pain from the upper trapezius muscle - is frequent in female employees in monotonous stressful jobs, potentially due to chronic overload of type I muscle fibers. In this study, we investigated the... more
    Trapezius myalgia - chronic pain from the upper trapezius muscle - is frequent in female employees in monotonous stressful jobs, potentially due to chronic overload of type I muscle fibers. In this study, we investigated the intra-individual distribution of trapezius muscle fiber size, and hypothesized that females with myalgia compared with matched healthy controls have a higher percentage of grossly hypertrophied type I fibers with poor capillarization. Forty-two female office workers with trapezius myalgia (MYA) and 20 healthy matched controls (CON) participated in the study. Standard histochemical methods were used to determine fiber size, fiber type, and capillarization. Type I megafiber were defined as at least twice the size of the median type I fiber size of each individual. The main finding was that MYA had a significantly higher proportion of type I megafibers than CON, in spite of no significant difference in overall type I fiber size. In MYA and CON type I megafibers were located in 46% and 11% of the females, respectively. Capillarization of the overall type I fiber pool was not different between CON and MYA, but was significantly lower in type I megafibers of both groups. The percentage of megafibers was positively related to age and weekly working hours, indicating an effect of long-term exposure. In conclusion, this study shows that trapezius myalgia is associated with a significantly higher percentage of grossly hypertrophied type I muscle fibers with poor capillarization - type I megafibers.
    Acute muscle protein metabolism is modulated not only by resistance exercise but also by amino acids. However, less is known about the long-term hypertrophic effect of protein supplementation in combination with resistance training. The... more
    Acute muscle protein metabolism is modulated not only by resistance exercise but also by amino acids. However, less is known about the long-term hypertrophic effect of protein supplementation in combination with resistance training. The present study was designed to compare the effect of 14 weeks of resistance training combined with timed ingestion of isoenergetic protein vs carbohydrate supplementation on muscle fiber hypertrophy and mechanical muscle performance. Supplementation was administered before and immediately after each training bout and, in addition, in the morning on nontraining days. Muscle biopsy specimens were obtained from the vastus lateralis muscle and analyzed for muscle fiber cross-sectional area. Squat jump and countermovement jump were performed on a force platform to determine vertical jump height. Peak torque during slow (30 degrees s-1) and fast (240 degrees s-1) concentric and eccentric contractions of the knee extensor muscle was measured in an isokinetic dynamometer. After 14 weeks of resistance training, the protein group showed hypertrophy of type I (18% +/- 5%; P < .01) and type II (26% +/- 5%; P < .01) muscle fibers, whereas no change above baseline occurred in the carbohydrate group. Squat jump height increased only in the protein group, whereas countermovement jump height and peak torque during slow isokinetic muscle contraction increased similarly in both groups. In conclusion, a minor advantage of protein supplementation over carbohydrate supplementation during resistance training on mechanical muscle function was found. However, the present results may have relevance for individuals who are particularly interested in gaining muscle size.
    To better understand how immobilization and surgery affect muscle size and function in the elderly and to identify effective training regimes. A prospective randomized, controlled study. Bispebjerg University Hospital, Copenhagen,... more
    To better understand how immobilization and surgery affect muscle size and function in the elderly and to identify effective training regimes. A prospective randomized, controlled study. Bispebjerg University Hospital, Copenhagen, Denmark. Thirty-six patients (aged 60-86) scheduled for unilateral hip replacement due to primary hip osteoarthrosis. Patients were randomized to standard home-based rehabilitation (1 h/d x 12 weeks), unilateral neuromuscular electrical stimulation of the operated side (1 h/d x 12 weeks), or unilateral resistance training of the operated side (3/wk x 12 weeks). Hospital length of stay (LOS), quadriceps muscle cross-sectional area (CSA), isokinetic muscle strength, and functional performance. Patients were tested presurgery and 5 and 12 weeks postsurgery. Mean+/-standard error LOS was shorter for the resistance training group (10.0+/-2.4 days, P<.05) than for the standard rehabilitation group (16.0+/-7.2 days). Resistance training, but not electrical stimulation or standard rehabilitation, resulted in increased CSA (12%, P<.05) and muscle strength (22-28%, P<.05). Functional muscle performance increased after resistance training (30%, P<.001) and electrical stimulation (15%, P<.05) but not after standard rehabilitation. Postoperative resistance training effectively increased maximal muscle strength, muscle mass, and muscle function more than a standard rehabilitation regime. Furthermore, it markedly reduced LOS in elderly postoperative patients.
    We examined the physical demands of small-sided soccer games in untrained middle-age males and muscle adaptations and performance effects over 12 weeks of recreational soccer training in comparison with continuous running. Thirty-eight... more
    We examined the physical demands of small-sided soccer games in untrained middle-age males and muscle adaptations and performance effects over 12 weeks of recreational soccer training in comparison with continuous running. Thirty-eight healthy subjects (20-43 years) were randomized into a soccer (SO), running (RU) and control (CO) group. Two-three weekly 1-h training sessions were performed. Muscle lactate (30.1 +/- 4.1 vs. 15.6 +/- 3.3 mmol/kg d.w.), blood lactate, blood glucose and time above 90% HR(max) (20 +/- 4% vs. 1 +/- 1%) were higher (p < 0.05) during training in SO than in RU. After 12 weeks of training, quadriceps muscle mass and mean muscle fibre area were 9 and 15% larger (p < 0.05) in SO, but unaltered in RU, and in SO, the fraction of FTx fibres was lowered (10.7 +/- 1.8 vs. 17.9 +/- 3.2%). In SO, citrate synthase activity was 10 and 14% higher (p < 0.05) after 4 and 12 weeks, but unaltered in RU. After 4 weeks VO(2max) and Yo-Yo IE2 performance were elevated (p < 0.05) to a similar extent in SO (7 and 37%) and RU (6 and 36%) but increased further (p…
    Real-time harmonic contrast-enhanced ultrasound (CEU) is used in several diseases to visualize the microvascularization in various tissues, due to its high sensitivity. The aim of the present study was to investigate whether CEU could be... more
    Real-time harmonic contrast-enhanced ultrasound (CEU) is used in several diseases to visualize the microvascularization in various tissues, due to its high sensitivity. The aim of the present study was to investigate whether CEU could be used to detect an increase in the microvascular volume (MV) in healthy tendon tissue in response to exercise comprising a 1-h run. After a bolus injection of the ultrasound contrast SonoVue(®), CEU measurements of (MV) in the Achilles tendon were taken prior to exercise, immediately after a 1-h run, and 24 h after exercise in nine healthy young subjects (seven men and two women) mean age 31 ± 4 years. In addition, the effect of 15 min of arm cycling exercise on the flow within the Achilles tendon was tested in four athletes (mean age 33 ± 6 years) using the CEU method before and after exercise. The present data show a significant increase in the (MV) of the Achilles tendon for all subjects following the run compared with before exercise. No significant change in (MV) was seen in the Achilles tendon after 15-min arm cycling exercise (P = 0·96). This indicates that the increase in microvascular blood volume within the Achilles tendon in response to running is a local response. The present data reveal that real-time harmonic CEU can be used to determine the MV of healthy Achilles tendons both at rest and after 1 h of running exercise.
    Research Interests:
    Achilles tendinopathy (AT) is initiated asymptomatically and is therefore often discovered at a very late stage. To elucidate whether the microvascular volume (MV) of the Achilles tendon is elevated in patients with AT compared with... more
    Achilles tendinopathy (AT) is initiated asymptomatically and is therefore often discovered at a very late stage. To elucidate whether the microvascular volume (MV) of the Achilles tendon is elevated in patients with AT compared with healthy controls during pre-exercise rest, after acute exercise, and 24 hours after exercise. Additionally, this study investigated the muscle activation pattern of the gastrocnemius muscle and the relative elasticity of the Achilles tendon during a 1-hour treadmill run in healthy patients and in patients with AT. Controlled laboratory study. Real-time harmonic contrast-enhanced ultrasound (CEU) measurements of the MV of the Achilles tendon were taken in 18 volunteers (9 patients with AT, 9 healthy controls). The CEU analyses were conducted before exercise, immediately after a 1-hour treadmill run, and 24 hours after exercise. Surface electromyography (EMG) signals of the gastrocnemius were recorded continuously during the 1-hour treadmill run. In both the controls and the patients with AT, the MV of the Achilles tendon was increased after exercise as compared with before exercise (P < .005). Additionally, the MV signal was significantly larger in the patients with AT before, immediately after, and 24 hours after the running exercise compared with values in healthy controls (P < .0001). The muscle activation pattern differed in patients with AT compared with controls in that controls had increased EMG amplitudes at the end of the 1-hour treadmill run in the medial and lateral gastrocnemius (P < .0001). Moreover, patients with AT had approximately 15% less elastic Achilles tendons at the beginning of the 1-hour treadmill run, a condition that did not change because of exercise. Acute exercise increases the MV of the Achilles tendon in healthy patients and patients with AT in a similar manner. However, patients with AT have a significantly larger MV at all time points compared with healthy patients, supporting the hypothesis that microvascular changes may be involved in the pathogenesis of tendinopathy. This study underlines that tendon flexibility is altered in patients with AT and that CEU is a promising tool to establish the early diagnosis of this condition.
    With advancements in electronics technology, the new-era of devices are flexible and bendable. This has given rise to new smart textiles as wearables. Printed electronics enables to put down electronics on textiles without affecting the... more
    With advancements in electronics technology, the new-era of devices are flexible and bendable. This has given rise to new smart textiles as wearables. Printed electronics enables to put down electronics on textiles without affecting the flexibility of the fabric. We have developed dry electrodes on healthcare stockings to stimulate muscles to preserve muscle mass in COVID-19 patients. The fabric does not allow direct printing of electronics. Thus, various layers are used. This paper investigates the mechanical strength of these layers on the stocking to remain functional for daily usage. We also discuss washing results on the layers.
    Using muscle functional MRI (mfMRI), this study was able to differentiate the acute physiological responses following three established hypertrophic resistance exercise strategies. Low-load exercise protocols performed to failure, with or... more
    Using muscle functional MRI (mfMRI), this study was able to differentiate the acute physiological responses following three established hypertrophic resistance exercise strategies. Low-load exercise protocols performed to failure, with or without blood flow restriction, resulted in larger changes in R2 (i.e. greater T2-shifts) with a slow rate of return to baseline indicative of myocellular fluid shifts. These data were cross evaluated with interleaved measures of macrovascular blood flow, water diffusion, muscle cross sectional area (i.e. acute macroscopic muscle swelling), and intracellular water fraction measured using MRI.
    Acute changes in blood flow, diffusion, blood oxygenation, cross-sectional area, and the “T2 shift” are evaluated in human skeletal muscle in response to blood flow-restricted (BFR) and conventional free-flow knee extensor exercise... more
    Acute changes in blood flow, diffusion, blood oxygenation, cross-sectional area, and the “T2 shift” are evaluated in human skeletal muscle in response to blood flow-restricted (BFR) and conventional free-flow knee extensor exercise performed in an MRI scanner. The acute physiological response to exercise was dependent on the magnitude of load and the application of BFR. Physiological variables changed markedly and established a steady state rapidly after the first of four exercise sets.
    IntroductionSarcopenia is generally used to describe the age-related loss of muscle mass and strength believed to play a major role in the pathogenesis of physical frailty and functional impairment that may occur with old age. The... more
    IntroductionSarcopenia is generally used to describe the age-related loss of muscle mass and strength believed to play a major role in the pathogenesis of physical frailty and functional impairment that may occur with old age. The knowledge surrounding the prevalence and determinants of sarcopenia in older medical patients is scarce, and it is unknown whether specific biomarkers can predict physical deconditioning during hospitalisation. We hypothesise that a combination of clinical, functional and circulating biomarkers can serve as a risk stratification tool and can (i) identify older acutely ill medical patients at risk of prolonged hospital stays and (ii) predict changes in muscle mass, muscle strength and function during hospitalisation.Method and analysisThe Copenhagen PROTECT study is a prospective cohort study consisting of acutely ill older medical patients admitted to the acute medical ward at Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark. Assessmen...
    This study aimed to assess the validity and functional relevance of a standardized procedure to assess lower limb muscle power by means of the 30-s sit-to-stand (STS) test when compared to leg extension power (LEP), traditional STS... more
    This study aimed to assess the validity and functional relevance of a standardized procedure to assess lower limb muscle power by means of the 30-s sit-to-stand (STS) test when compared to leg extension power (LEP), traditional STS performance and handgrip strength. A total of 628 community-dwelling older subjects (60–93 years) from the Copenhagen Sarcopenia Study were included. Physical performance was assessed by the 30-s STS and 10-m maximal gait speed tests. Handgrip strength and LEP were recorded by a hand-held dynamometer and the Nottingham power rig, respectively. STS muscle power was calculated using the subjects’ body mass and height, chair height and the number of repetitions completed in the 30-s STS test. We found a small albeit significant difference between LEP and unilateral STS power in older men (245.5 ± 88.8 vs. 223.4 ± 81.4 W; ES = 0.26; p < 0.05), but not in older women (135.9 ± 51.9 vs. 138.5 ± 49.6 W; ES = 0.05; p > 0.05). Notably, a large positive correl...
    Mitochondrial energy production involves the movement of protons down a large electrochemical gradient through ATP synthase located on the folded inner membrane, known as cristae. In mammalian skeletal muscle, the density of cristae in... more
    Mitochondrial energy production involves the movement of protons down a large electrochemical gradient through ATP synthase located on the folded inner membrane, known as cristae. In mammalian skeletal muscle, the density of cristae in mitochondria is thought to be constant. However, recent experimental studies have shown that respiration per mitochondria varies.Modelling studies have hypothesised that this variation in respiration per mitochondria depends on plasticity in cristae density, but currently evidence for such a mechanism is lacking. Here, we confirm this hypothesis by showing that, in human skeletal muscle, contrary to the current view, the mitochondrial cristae density is not constant, but exhibits plasticity with long-term endurance training. Furthermore, we show that frequently recruited mitochondria-enriched fibres have significantly increased cristae density and that, at whole-body level, muscle mitochondrial cristae density is a better predictor of maximal oxygen u...
    The present study describes the assessment of true formation of type III collagen in different pathologies using a neo-epitope specific competitive Enzyme-linked immunosorbent assay (ELISA) towards the N-terminal propeptide of type III... more
    The present study describes the assessment of true formation of type III collagen in different pathologies using a neo-epitope specific competitive Enzyme-linked immunosorbent assay (ELISA) towards the N-terminal propeptide of type III collagen (PRO-C3). The monoclonal antibody was raised against the N-protease mediated cleavage site of the N-terminal propeptide of type III collagen and a competitive ELISA was developed using the selected antibody. The assay was evaluated in relation to neo-epitope specificity, technical performance, and as a marker for liver fibrosis and muscle mass using the rat carbon tetrachloride (CCl4) model and a study of immobilization induced muscle loss in humans, respectively. The ELISA was neo-epitope specific, technically stable and can be assessed in serum and plasma samples. In the CCl4 liver fibrosis model it was observed that serum PRO-C3 were significantly elevated in rats with liver fibrosis as seen by histology (56% elevated in the highest quarti...
    Immobilization-induced loss of muscle mass is a complex phenomenon with several parallels to sarcopenic and cachectic muscle loss. Muscle is a large organ with a protein turnover that is orders of magnitude larger than most other tissues.... more
    Immobilization-induced loss of muscle mass is a complex phenomenon with several parallels to sarcopenic and cachectic muscle loss. Muscle is a large organ with a protein turnover that is orders of magnitude larger than most other tissues. Thus, we hypothesize that muscle loss and regain is reflected by peptide biomarkers derived from type VI collagen processing released in the circulation. In order to test this hypothesis, we set out to develop an ELISA assay against an type VI collagen N-terminal globular domain epitope (IC6) and measured the levels of IC6 and an MMP-generated degradation fragment of collagen 6, (C6M) in a human immobilization-remobilization study setup with young (n = 11) and old (n = 9) men. They were subjected to 2 weeks of unilateral lower limb immobilization followed by 4 weeks of remobilization including thrice weekly resistance training, using the contralateral leg as internal controls. Subjects were sampled for strength, quadriceps muscle volume and blood a...

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