GDF-15 is associated with sarcopenia and frailty in acutely admitted older medical patients.

BACKGROUND: Growth differentiation factor-15 (GDF-15) has been associated with senescence, lower muscle strength, and physical performance in healthy older people. Still, it is not clear whether GDF-15 can be utilized as a biomarker of sarcopenia and frailty in the early stages of hospitalization. We investigated the association of plasma GDF-15 with sarcopenia and frailty in older, acutely admitted medical patients. METHODS: The present study is based on secondary analyses of cross-sectional data from the Copenhagen PROTECT study, a prospective cohort study including 1071 patients ≥65 years of age admitted to the acute medical ward at Copenhagen University Hospital, Bispebjerg, Denmark. Muscle strength was assessed using handgrip strength, and lean mass was assessed using direct segmental multifrequency bioelectrical impedance analyses and used to clarify the potential presence of sarcopenia defined according to guidelines from the European Working Group on Sarcopenia in Older People. Frailty was evaluated using the Clinical Frailty Scale. Plasma GDF-15 was measured using electrochemiluminescence assays from Meso Scale Discovery (MSD, Rockville, MD, USA). RESULTS: We included 1036 patients with completed blood samples (mean age 78.9 ± 7.8 years, 53% female). The median concentration of GDF-15 was 2669.3 pg/mL. Systemic GDF-15 was significantly higher in patients with either sarcopenia (P < 0.01) or frailty (P < 0.001) compared with patients without the conditions. Optimum cut-off points of GDF-15 relating to sarcopenia and frailty were 1541 and 2166 pg/mL, respectively. CONCLUSIONS: Systemic GDF-15 was higher in acutely admitted older medical patients with sarcopenia and frailty compared with patients without. The present study defined the optimum cut-off for GDF-15, related to the presence of sarcopenia and frailty, respectively. When elevated above the derived cutoffs, GDF-15 was strongly associated with frailty and sarcopenia in both crude and fully adjusted models.

Ventilation perfusion functional difference images in lung SPECT: A linear and symmetrical scale as an alternative to the ventilation perfusion ratio.

PURPOSE: Ventilation Perfusion SPECT is important in the diagnostics of e.g. pulmonary embolism and chronic obstructive pulmonary disease. Classical and reverse mismatched defects can be identified by utilizing the ventilation-perfusion ratio. Unfortunately, this ratio is only linear in the ventilation, the scale is not symmetrical regarding classical and reversed mismatches and small perfusion values give rise to artifacts. The ventilation-perfusion (VQ) difference is developed as an alternative. METHODS: For both VQ-ratio and VQ-difference a scaling factor for the perfusion is computed, so that voxels with matched ventilation and perfusion (on average) yield zero signal. The relative VQ-difference is calculated by scaling with the summed VQ-signal in each voxel. The scaled VQ-difference is calculated by scaling with the global maximum of this sum. RESULTS: The relative and scaled differences have a scale from -1 (perfusion only) to + 1 (ventilation only). Image quality of relative VQ-difference and VQ-ratio images is hampered by artifacts from areas with both low perfusion and low ventilation. Ratio and differences have been investigated in ten patients and are shown for three patients (one without defects). Clinical thresholds for the difference images are derived resulting in color maps of relevant (reversed) mismatches with a (reciprocal) ratio larger than two. CONCLUSIONS: The relative ventilation-perfusion difference is a methodological improvement on the ventilation-perfusion ratio, because it has a symmetrical scale and is bound on a closed domain. A better diagnostic value is expected by utilizing the scaled difference, which represents functional difference instead of relative difference.

Self-help interventions for persistent physical symptoms: a systematic review of behaviour change components and their potential effects.

Persistent physical symptoms (PPS) remain a challenge in the healthcare system due to time-constrained consultations, uncertainty and limited specialised care capacity. Self-help interventions may be a cost-effective way to widen the access to treatment. As a foundation for future interventions, we aimed to describe intervention components and their potential effects in self-help interventions for PPS. A systematic literature search was made in PubMed, EMBASE, PsycINFO and CENTRAL. Fifty-one randomised controlled trials were included. Interventions were coded for effect on outcomes (standardised mean difference ≥0.2) related to symptom burden, anxiety, depression, quality of life, healthcare utilisation and sickness absence. The Behaviour Change Technique (BCT) Taxonomy v1 was used to code intervention components. An index of potential was calculated for each BCT within an outcome category. Each BCT was assessed as 'potentially effective' or 'not effective' based on a two-sided test for binomial random variables. Sixteen BCTs showed potential effect as treatment components. These BCTs represented the themes: goals and planning, feedback and monitoring, shaping knowledge, natural consequences, comparison of behaviour, associations, repetition and substitution, regulation, antecedents and identity. The results suggest that specific BCTs should be included in new PPS self-help interventions aiming to improve the patients' physical and mental health.

Physiological and clinical effects of low-intensity blood-flow restricted resistance exercise compared to standard rehabilitation in adults with knee osteoarthritis-Protocol for a randomized controlled trial.

INTRODUCTION: Osteoarthritis (OA) is a common disease with high socioeconomical costs. In Denmark, standard rehabilitation (SR) consists of a combination of patient education and supervised physical exercise involving a standardized neuromuscular training program. As an evidence-based alternative, high-load (>70% 1RM) resistance training (HIRT) has shown positive rehabilitation effects in knee-OA but may not be tolerated in all patients (~25%) due to knee joint pain. However, low-load resistance training (20-40% 1RM) with concurrent partial blood-flow restriction (BFR) appears to produce effects similar to HIRT yet involving reduced joint pain during and after exercise. The aim is to examine the effect of low-load BFR training compared to SR on pain, thigh muscle mass and muscle function in adults with knee-OA. We hypothesize that 12 weeks of BFR will lead to superior improvements in pain, muscle mass and mechanical muscle function compared to SR. METHODS AND ANALYSIS: 90 participants diagnosed with radiographic knee-OA will be randomized to either BFR or SR twice a week for 12 weeks. BFR will consist of two selected lower limb strength exercises performed with an inflated pneumatic occlusion cuff. Intervention procedures in SR consist of a full 8 weeks GLA:D course followed by 4 weeks of team group training. Primary outcome variable is the change in KOOS-Pain subscale from baseline to 12 weeks. Secondary outcome variables are changes in pain sensitivity, functional performance, muscle mass and mechanical muscle function. Intention-to-treat and per-protocol analyses will be conducted. One-way analysis of variance will be performed to evaluate between-group changes. Pre-to-post intervention comparisons will be analyzed using a mixed linear model. Regression analysis will be performed to evaluate potential associations between selected outcome variables.

Feasibility of Assessing Older Patients in the Acute Setting: Findings From the Copenhagen PROTECT Study.

OBJECTIVES: Older patients are typically underrepresented in clinical trials despite representing a major proportion of the patient population. We aim to describe the feasibility of performing body composition measures, physical function measures, and patient-reported questionnaires within the first 24 hours of admission in a large sample of older acutely admitted medical patients. In addition, we aim to characterize patients with missing measurements. DESIGN: Secondary analyses of cross-sectional data from a cohort study. SETTING AND PARTICIPANTS: A total of 1071 acutely admitted patients aged ≥65 years from the acute medical ward at Bispebjerg Hospital, were enrolled within the first 24 hours of hospitalization. METHODS: Body composition was investigated using direct segmental multifrequency bioelectrical impedance analyses (DSM-BIA) and physical function was assessed using hand grip strength (HGS) and the 30-second sit-to-stand test (STS). The orientation-memory-concentration test (OMC) was used to evaluate the prevalence of cognitive impairments within 24 hours of hospitalization, and the OMC in conjunction with the Strength, Assistance walking, Rise from a chair, Climb stairs, and Falls questionnaire (SARC-F) was used to assess the feasibility of patient-reported outcomes (PROs). RESULTS: Mean age was 78.8 ± 7.8 years (53.0% female). HGS was performed in 96.2% of the enrolled patients, whereas the PRO, 30-second STS, and DSM-BIA were performed in 91.2%, 69.2%, and 59.8% of patients, respectively. The main barrier for performing the 30-second STS and body composition measurements was an inability to mobilize the patient from the hospital bed. CONCLUSIONS AND IMPLICATIONS: The assessment of HGS and PROs show excellent feasibility in clinical research including older patients, even when the patients are enrolled and tested within 24 hours of an acute admission. Assessments of DSM-BIA and the 30-second STS show good feasibility but are less feasible in immobile patients often presenting as more frail, weaker, and cognitively impaired.

Effect of atropine and propofol on the minimum anaesthetic concentration of isoflurane in the freshwater turtle Trachemys scripta (yellow-bellied slider).

OBJECTIVE: To determine if the administration of atropine would reduce the measured minimum anaesthetic concentration of isoflurane (MACisoflurane) in freshwater turtles - the yellow-bellied slider (Trachemys scripta scripta). STUDY DESIGN: Paired, blinded, randomized, prospective studies of 1) the effect of atropine in isoflurane anaesthetized freshwater turtles (T. scripta scripta) and 2) the effect of atropine in yellow-bellied sliders in which anaesthesia was induced with propofol and maintained with isoflurane. ANIMALS: T. scripta scripta (n = 8), female, adult. METHODS: Atropine (2 mg kg-1) or an isovolumetric control injection of saline was administered intraperitoneally 15 minutes prior to induction of anaesthesia with isoflurane. Individual MACisoflurane was then determined by end-tidal gas analysis in a bracketing design by an experimenter blinded to the administered drug, with a 2 week washout period. The experiment was repeated, with atropine (2 mg kg-1) or saline administered intravascularly in combination with propofol for anaesthetic induction. Linear mixed modelling was used to determine the effects of atropine and propofol on the individual MACisoflurane. Data are presented as mean ± standard deviation. RESULTS: Premedication with atropine significantly reduced MACisoflurane (p = 0.0039). In isoflurane-induced T. scripta scripta, MACisoflurane decreased from 4.2 ± 0.4% to 3.3 ± 0.8% when atropine had been administered. Propofol as an induction agent had a MAC-sparing effect (p < 0.001) such that MACisoflurane following propofol and a control injection of saline was 2.3 ± 1.0%, which decreased further to 1.5 ± 0.8% when propofol was combined with atropine. CONCLUSIONS AND CLINICAL RELEVANCE: Atropine, presumably by inhibiting parasympathetically mediated pulmonary artery constriction, decreases right-to-left cardiac shunting and the MACisoflurane in yellow-bellied sliders, and thereby may facilitate control of inhalant anaesthesia. Propofol can be used for induction of anaesthesia and reduces the required concentration of inhaled anaesthesia assessed 1.5 hours following induction.

Printed dry electrode for neuromuscular electrical stimulation (NMES) for e-textile.

Muscle atrophy is a well-known consequence of immobilization and critical illness, leading to prolonged rehabilitation and increased mortality. In this study, we develop a solution to preserve muscle mass using customized biocompatible neuromuscular electrical stimulation (NMES) device. Commercially available NMES solutions with gel-based electrodes often lead to skin irritation. We demonstrate the printing of conducting electrodes on a compressive stocking textile that can be used for more than seven days without observing any inflammation. This solution consists of a dry and biocompatible electrode directly integrated into the textile with good mechanical compatibility with skin (Young's modulus of 0.39 MPa). The surface roughness of the underlying substrate plays a significant role in obtaining good print quality. Electrochemical Impedance Spectroscopy (EIS) analysis showed that the printed electrode showed better performance than the commercial ones based on a matched interfacial performance and improved series resistance. Furthermore, we investigated our NMES solution in a hospital setting to evaluate its effectiveness on muscle atrophy, with promising results.

Why freebirth in a maternity system with free midwifery care? A qualitative study of Danish women's motivations and preparations for freebirth.

OBJECTIVE: Even in maternity care systems with free midwifery care, some women intentionally choose to birth unattended by any health professional (freebirth). Women who choose freebirth represent an enigma for many, and a provocation to some. However, people who do not conform to dominant medical practices are a source of valuable insights that can reveal shortcomings in the mainstream health care system. Thus, the aim of this study was to explore and understand women's motivations and preparations for freebirth. METHODS: The study was informed by the theoretical lens of the 'undisciplined patient'. Qualitative, in-depth interviews were performed with ten Danish women, who for their most recent birth had planned to freebirth. Data were analysed using reflexive thematic analysis. RESULTS: Four themes were identified. "The standard system is not for me" describes negative experiences during previous births and the desire for more individualised support. "Re-establishing trust in myself" describes the women's quest for recognizing their own needs and re-building autonomy and inner strength. "I do my research" describes how the women sought new ways of knowing and prioritised experiential knowledge. And finally, "I create my safe space" describes the women's efforts to create the best possible physical and emotional space for themselves and their babies in order to have a safe and autonomous birth experience. CONCLUSION: Freebirth is not undertaken lightly or without preparation by women. Improved continuity of care as well as greater flexibility in hospital guidelines could accommodate some of these women's demand for autonomy in birth.

Profiling the Atopic Dermatitis Epidermal Transcriptome by Tape Stripping and BRB-seq.

Tape stripping is a non-invasive skin sampling technique, which has recently gained use for the study of the transcriptome of atopic dermatitis (AD), a common inflammatory skin disorder characterized by a defective epidermal barrier and perturbated immune response. Here, we performed BRB-seq-a low cost, multiplex-based, transcriptomic profiling technique-on tape-stripped skin from 30 AD patients and 30 healthy controls to evaluate the methods' ability to assess the epidermal AD transcriptome. An AD signature consisting of 91 differentially expressed genes, specific for skin barrier and inflammatory response, was identified. The gene expression in the outermost layers, stratum corneum and stratum granulosum, of the skin showed highest correlation between tape-stripped skin and matched full-thickness punch biopsies. However, we observed that low and highly variable transcript counts, probably due to low RNA yield and RNA degradation in the tape-stripped skin samples, were a limiting factor for epidermal transcriptome profiling as compared to punch biopsies. We conclude that deep BRB-seq of tape-stripped skin is needed to counteract large between-sample RNA yield variation and highly zero-inflated data in order to apply this protocol for population-wide screening of the epidermal transcriptome in inflammatory skin diseases.

Assessment of Liver Fat: Dual-Energy CT versus Conventional CT with and without Contrast.

We assessed the correlation between liver fat percentage using dual-energy CT (DECT) and Hounsfield unit (HU) measurements in contrast and non-contrast CT. This study included 177 patients in two patient groups: Group A (n = 125) underwent whole body non-contrast DECT and group B (n = 52) had a multiphasic DECT including a conventional non-contrast CT. Three regions of interest were placed on each image series, one in the left liver lobe and two in the right to measure Hounsfield Units (HU) as well as liver fat percentage. Linear regression analysis was performed for each group as well as combined. Receiver operating characteristic (ROC) curve was generated to establish the optimal fat percentage threshold value in DECT for predicting a non-contrast threshold of 40 HU correlating to moderate-severe liver steatosis. We found a strong correlation between fat percentage found with DECT and HU measured in non-contrast CT in group A and B individually (R2 = 0.81 and 0.86, respectively) as well as combined (R2 = 0.85). No significant difference was found when comparing venous and arterial phase DECT fat percentage measurements in group B (p = 0.67). A threshold of 10% liver fat found with DECT had 95% sensitivity and 95% specificity for the prediction of a 40 HU threshold using non-contrast CT. In conclusion, liver fat quantification using DECT shows high correlation with HU measurements independent of scan phase.

Site-specific functional roles of the Factor X activation peptide in the intrinsic tenase-mediated Factor X activation.

The conversion of zymogen Factor X (FX) to an active protease involves the removal of a 52-residue long activation peptide (AP). Through site-directed mutagenesis, we investigate the role of the AP and demonstrate that the high abundance of proline residues is important for efficient proteolysis of FX. Moreover, we identify an essential interaction site for Factor IXa (FIXa) between residues 22 and 30 (AP numbering) and find that the residues between 31 and 41 may provide an important interaction site for the intrinsic tenase complex, composed of Factor IXa (FIXa) and Factor VIIIa (FVIIIa). Finally, we suggest that the carbohydrate chain at Asn-39 restricts the activator specificity, as elimination of this glycosylation site increases the activation rate for activation by FIXa and FXa.

Assessment of functional sit-to-stand muscle power: Cross-sectional trajectories across the lifespan.

BACKGROUND: The 30-s sit-to-stand (STS) muscle power test is a valid test to assess muscle power in older people; however, whether it may be used to assess trajectories of lower-limb muscle power through the adult lifespan is not known. This study evaluated the pattern and time course of variations in relative, allometric and specific STS muscle power throughout the lifespan. METHODS: Subjects participating in the Copenhagen Sarcopenia Study (729 women and 576 men; aged 20 to 93 years) were included. Lower-limb muscle power was assessed with the 30-s version of the STS muscle power test. Allometric, relative and specific STS power were calculated as absolute STS power normalized to height squared, body mass and leg lean mass as assessed by DXA, respectively. RESULTS: Relative STS muscle power tended to increase in women (0.08 ±â€¯0.05 W·kg-1·yr-1; p = 0.082) and increased in men (0.14 ±â€¯0.07 W·kg-1·yr-1; p = 0.046) between 20 and 30 years, followed by a slow decline (-0.05 ±â€¯0.05 W·kg-1·yr-1 and -0.06 ±â€¯0.08 W·kg-1·yr-1, respectively; both p > 0.05) between 30 and 50 years. Then, relative STS power declined at an accelerated rate up to oldest age in men (-0.09 ±â€¯0.02 W·kg-1·yr-1) and in women until the age of 75 (-0.09 ±â€¯0.01 W·kg-1·yr-1) (both p < 0.001). A lower rate of decline was observed in women aged 75 and older (-0.04 ±â€¯0.02 W·kg-1·yr-1; p = 0.039). Similar age-related patterns were noted for allometric and specific STS power. CONCLUSIONS: The STS muscle power test appears to provide a feasible and inexpensive tool to monitor cross-sectional trajectories of muscle power throughout the lifespan.

[Electrical stimulation against loss of muscles and function in a patient admitted with COVID-19].

This is a case report of a hospitalised 62-year-old male patient with COVID-19, who received unilateral neuromuscular electrical stimulation treatment with a customised anti-embolic compression stocking and maintained muscle mass as well as maximum voluntary quadriceps contraction and balance during six days of illness-induced immobilisation. This illustrates, that short durations of neuromuscular electrical stimulation can help maintaining muscle mass and physical function in patients with SARS-CoV-2.

Exercise-induced fluid shifts are distinct to exercise mode and intensity: a comparison of blood flow-restricted and free-flow resistance exercise.

MRI can provide fundamental tools in decoding physiological stressors stimulated by training paradigms. Acute physiological changes induced by three diverse exercise protocols known to elicit similar levels of muscle hypertrophy were evaluated using muscle functional magnetic resonance imaging (mfMRI). The study was a cross-over study with participants (n = 10) performing three acute unilateral knee extensor exercise protocols to failure and a work matched control exercise protocol. Participants were scanned after each exercise protocol; 70% 1 repetition maximum (RM) (FF70); 20% 1RM (FF20); 20% 1RM with blood flow restriction (BFR20); free-flow (FF) control work matched to BFR20 (FF20WM). Post exercise mfMRI scans were used to obtain interleaved measures of muscle R2 (indicator of edema), R2' (indicator of deoxyhemoglobin), muscle cross sectional area (CSA) blood flow, and diffusion. Both BFR20 and FF20 exercise resulted in a larger acute decrease in R2, decrease in R2', and expansion of the extracellular compartment with slower rates of recovery. BFR20 caused greater acute increases in muscle CSA than FF20WM and FF70. Only BFR20 caused acute increases in intracellular volume. Postexercise muscle blood flow was higher after FF70 and FF20 exercise than BFR20. Acute changes in mean diffusivity were similar across all exercise protocols. This study was able to differentiate the acute physiological responses between anabolic exercise protocols. Low-load exercise protocols, known to have relatively higher energy contributions from glycolysis at task failure, elicited a higher mfMRI response. Noninvasive mfMRI represents a promising tool for decoding mechanisms of anabolic adaptation in muscle.NEW & NOTEWORTHY 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.

Real-Time Decoding of Attentional States Using Closed-Loop EEG Neurofeedback.

Sustained attention is a cognitive ability to maintain task focus over extended periods of time (Mackworth, 1948; Chun, Golomb, & Turk-Browne, 2011). In this study, scalp electroencephalography (EEG) signals were processed in real time using a 32 dry-electrode system during a sustained visual attention task. An attention training paradigm was implemented, as designed in DeBettencourt, Cohen, Lee, Norman, and Turk-Browne (2015) in which the composition of a sequence of blended images is updated based on the participant's decoded attentional level to a primed image category. It was hypothesized that a single neurofeedback training session would improve sustained attention abilities. Twenty-two participants were trained on a single neurofeedback session with behavioral pretraining and posttraining sessions within three consecutive days. Half of the participants functioned as controls in a double-blinded design and received sham neurofeedback. During the neurofeedback session, attentional states to primed categories were decoded in real time and used to provide a continuous feedback signal customized to each participant in a closed-loop approach. We report a mean classifier decoding error rate of 34.3% (chance = 50%). Within the neurofeedback group, there was a greater level of task-relevant attentional information decoded in the participant's brain before making a correct behavioral response than before an incorrect response. This effect was not visible in the control group (interaction p=7.23e-4), which strongly indicates that we were able to achieve a meaningful measure of subjective attentional state in real time and control participants' behavior during the neurofeedback session. We do not provide conclusive evidence whether the single neurofeedback session per se provided lasting effects in sustained attention abilities. We developed a portable EEG neurofeedback system capable of decoding attentional states and predicting behavioral choices in the attention task at hand. The neurofeedback code framework is Python based and open source, and it allows users to actively engage in the development of neurofeedback tools for scientific and translational use.

Estimation of CARE Dose 4D quality reference mAs conversion factors for child to adult reference patient in child protocols on Siemens Symbia SPECT-CT systems.

OBJECTIVES: CARE Dose 4D modulates mAs through several mechanisms according to patient size and shape, whilst maintaining user-defined reference image quality on Siemens Symbia single-photon emission computed tomography (SPECT)-computed tomography (CT) systems. A 20 kg child reference was used in child protocols prior to software version VB10 and a 75 kg adult thereafter. Quality reference mAs conversion factors are estimated for delivering equivalent mAs to children between two comparable SPECT-CT systems using adult and child references for topogram-based patient-size-related dose level adaptations. METHODS: A child phantom was scanned using child protocols on a Siemens Symbia T16 (child reference) and a Siemens Symbia Intevo Bold (adult reference). On each system, scans of the thorax, abdomen and pelvis were acquired with arms up and down, at 80 and 110 kVp. Quality reference mAs settings of 10-50 were used on the Symbia T16 and 40-200 on the Symbia Intevo Bold. These data were used to propose quality reference mAs (adult/child reference) conversion factors according to scan range, arm position and tube voltage. RESULTS: Quality reference mAs for child protocols using the adult reference should multiply the child quality reference mAs by the following factors, to give comparable delivered mAs: arms up 80 kV: 3.8 (thorax), 3.8 (abdomen), 4.3 (pelvis); arms up at 110 kV: 3.8 (thorax), 4.1 (abdomen), 4.6 (pelvis); arms down at 80 kV: 4.0 (thorax), 3.7 (abdomen), 3.9 (pelvis); arms down at 110 kV: 4.3 (thorax), 4.0 (abdomen), 4.2 (pelvis). CONCLUSION: Conversion factors for child to adult dose modulation references are proposed, allowing comparable delivered mAs to a child.Video abstract: http://links.lww.com/NMC/A178.

Biomarkers for length of hospital stay, changes in muscle mass, strength and physical function in older medical patients: protocol for the Copenhagen PROTECT study-a prospective cohort study.

INTRODUCTION: Sarcopenia 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 ANALYSIS: The 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. Assessments are performed within 24 hours of admission and include blood samples, body composition, muscle strength, physical function and questionnaires. A subgroup of patients transferred to the Geriatric Department are included in a smaller geriatric cohort and have additional assessments at discharge to evaluate the relative change in circulating biomarker concentrations, body composition, muscle strength and physical function during hospitalisation. Enrolment commenced 4 November 2019, and proceeds until August 2021. ETHICS AND DISSEMINATION: The study protocol has been approved by the local ethics committee of Copenhagen and Frederiksberg (H-19039214) and the Danish Data Protection Agency (P-2019-239) and all experimental procedures were performed in accordance with the Declaration of Helsinki. Findings from the project, regardless of the outcome, will be published in relevant peer-reviewed scientific journals in online (www.clinicaltrials.gov). TRIAL REGISTRATION NUMBER: NCT04151108.

Physiological responses of human skeletal muscle to acute blood flow restricted exercise assessed by multimodal MRI.

Important physiological quantities for investigating muscle hypertrophy include blood oxygenation, cell swelling, and changes in blood flow. The purpose of this study was to compare the acute changes of these parameters in human skeletal muscle induced by low-load (20% 1-RM) blood flow-restricted (BFR-20) knee extensor exercise compared with free-flow work-matched (FF-20WM) and free-flow 50% 1-RM (FF-50) knee extensor exercise using multimodal magnetic resonance imaging (MRI). Subjects (n = 11) completed acute exercise sessions for each exercise mode in an MRI scanner, where interleaved measures of muscle R2 (indicator of edema), [Formula: see text] (indicator of deoxyhemoglobin), macrovascular blood flow, and diffusion were performed before, between sets, and after the final set for each exercise protocol. BFR-20 exercise resulted in larger acute decreases in R2 and greater increases in cross-sectional area than FF-20WM and FF-50 (P < 0.01). Blood oxygenation decreased between sets during BFR-20, as indicated by a 13.6% increase in [Formula: see text] values (P < 0.01)), whereas they remained unchanged for FF-20WM and decreased during FF-50 exercise. Quadriceps blood flow between sets was highest for the heavier load (FF-50), averaging 305 mL/min, and lowest for BFR-20 at 123 ± 73 mL/min until post-exercise cuff release, where blood flow rates in BFR-20 exceeded both FF protocols (P < 0.01). Acute changes in diffusion rates were similar for all exercise protocols. This study was able to differentiate the acute exercise response of selected physiological factors associated with skeletal muscle hypertrophy. Marked differences in these parameters were found to exist between BFR and FF exercise conditions, which contribute to explain the anabolic potential of low-load blood flow restricted muscle exercise.NEW & NOTEWORTHY 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.

Age- and Sex-Specific Changes in Lower-Limb Muscle Power Throughout the Lifespan.

BACKGROUND: Our main goal was to evaluate the pattern and time course of changes in relative muscle power and its constituting components throughout the life span. METHODS: A total of 1,305 subjects (729 women and 576 men; aged 20-93 years) participating in the Copenhagen Sarcopenia Study took part. Body mass index (BMI), leg lean mass assessed by dual-energy X-ray absorptiometry (DXA), and leg extension muscle power (LEP) assessed by the Nottingham power rig were recorded. Relative muscle power (normalized to body mass) and specific muscle power (normalized to leg lean mass) were calculated. Segmented regression analyses were used to identify the onset and pattern of age-related changes in the recorded variables. RESULTS: Relative muscle power began to decline above the age of 40 in both women and men, with women showing an attenuation of the decline above 75 years. Relative muscle power decreased with age due to (i) the loss of absolute LEP after the fourth decade of life and (ii) the increase in BMI up to the age of 75 years in women and 65 years in men. The decline in absolute LEP was caused by a decline in specific LEP up to the age of 75 in women and 65 in men, above which the loss in relative leg lean mass also contributed. CONCLUSIONS: Relative power decreased (i) above 40 years by the loss in absolute power (specific power only) and the increase in body mass, and (ii) above ~70 years by the loss in absolute power (both specific power and leg lean mass).