Exercise rehabilitation following intensive care unit discharge for recovery from critical illness: Executive summary of a Cochrane Collaboration systematic review

Skeletal muscle wasting and weakness are major complications of critical illness and underlie the profound physical and functional impairments experienced by survivors after discharge from the intensive care unit (ICU). Exercise-based rehabilitation has been shown to be beneficial when delivered during ICU admission. This review aimed to determine the effectiveness of exercise rehabilitation initiated after ICU discharge on primary outcomes of functional exercise capacity and health-related quality of life. We sought randomized controlled trials, quasi-randomized controlled trials, and controlled clinical trials comparing an exercise intervention commenced after ICU discharge vs. any other intervention or a control or ‘usual care’ programme in adult survivors of critical illness. Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database, and Cumulative Index to Nursing and Allied Health Literature databases were searched up to February 2015. Dual, independent screening of results, data extraction, and quality appraisal were performed. We included six trials involving 483 patients. Overall quality of evidence for both outcomes was very low. All studies evaluated functional exercise capacity, with three reporting positive effects in favour of the intervention. Only two studies evaluated health-related quality of life and neither reported differences between intervention and control groups. Meta-analyses of data were precluded due to variation in study design, types of interventions, and selection and reporting of outcome measurements. We were unable to determine an overall effect on functional exercise capacity or health-related quality of life of interventions initiated after ICU discharge for survivors of critical illness. Findings from ongoing studies are awaited. Future studies need to address methodological aspects of study design and conduct to enhance rigour, quality, and synthesis.

Botulinum toxin in masticatory muscles of the adult rat induces bone loss at the condyle and alveolar regions of the mandible associated with a bone proliferation at a muscle enthesis

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Macroalgae and commercial macroalgal polysaccharides as potential functional ingredients in muscle foods

Ulva rigida (UR) and Palmaria palmata (PP) were included in farmed Atlantic salmon diets at levels of 0-15% for 19 and 16 weeks, respectively. Quality and shelf-life parameters of salmon fillets stored in modified atmosphere packs (MAP) (60% N2 : 40% CO2) at 4ºC were compared to controls fed astaxanthin. Salmon fillets were enhanced with a yellow/orange colour. Proximate composition, pH and lipid oxidation were unaffected by dietary UR and PP. Salmon fed 5% UR and 5-15% PP did not influence sensory descriptors (texture, odour, oxidation flavour and overall acceptability) of cooked salmon fillets. Pig diets were supplemented with commercial wet- and spray-dried macroalgal (Laminaria digitata) polysaccharide extracts containing laminarin (L, 500 mg/kg feed) and fucoidan (F, 420 mg/kg feed) (L/F-WS, L/F-SD) for 3 weeks and quality and shelf-life parameters of fresh pork steaks (longissimus thoracis et lumborum) stored in MAP (80% O2 : 20% CO2) were examined. Level (450 or 900 mg L and F/kg feed) and duration (3 or 6 weeks) of dietary L/F-WS and mechanisms of antioxidant activities in pork were investigated. L/F-WS reduced (p < 0.05) lipid oxidation and lowered levels of saturated fatty acids in fresh pork after 3 weeks feeding. L/F-SD was added directly to mince pork (0.01 - 0.5%) and quality and shelf-life parameters of fresh pork patties stored in MAP (80% O2 : 20% CO2) were assessed. Direct addition of the L/F-SD increased levels of lipid oxidation and decreased surface redness (a* values) of fresh pork patties. Lipid oxidation was reduced in cooked patties due to the formation of Maillard reaction products. Cooked pork patties containing L/F-SD were subjected to an in vitro digestion and a cellular transwell model to confirm bioaccessibility and uptake of antioxidant compounds. In mechanistic studies, fucoidan demonstrated antiand pro-oxidant activities on muscle lipids and oxymyoglobin, respectively.

Grip strength and functional recovery after hip fracture: An observational study in elderly population

Muscle strength is a common issue in fragility syndrome and sarcopenia, both of them involved in the pathogenesis of falls and fractures. The objective is to study the relationship between hand grip strength and functional recovery after hip fracture surgery. This prospective observational study included patients aged 65. years and older who were admitted to hospital for hip fracture surgery during a 12 month period. Functional status (Barthel Index), mental status (Cruz Roja Index), hand grip strength, 25/OH-Vitamin D plasmatic levels were evaluated at admission. Follow-up was performed 3. months after discharge to assess functional status and survival. Correlations between hand grip strength and the rest of variables were evaluated. Univariate and multivariate analyses were further applied. Mean age of subjects was 85.1. ±. 0.63 years. Out of 127 subjects, 103 were women and 24 were men. Hand grip strength was obtained in 85 patients (76.5%) and, values were between 3.3 and 24.8. kg and 81 patients (95.2%) had values below cut-point of sarcopenia considering European Working Group of Sarcopenia criteria. Hand grip strength at admission shows significant association to Barthel index at three months and functional recovery. It is also associated with age (P <. 0.001) (r = 0.81), sex (P = 0.001), cognitive status by Cruz Roja Index (P <. 0.001) and functional status measured at admission by Barthel Index (P <. 0.01) (r = -0.22). Multivariate analysis confirmed that variables were independently associated to grip strength. Hand grip strength measured at admission in Orthogeriatric Unit after hip fracture is directly related to functional recovery in elderly patients.

Lateral bone density variations in the scoliotic spine

Adolescent Idiopathic Scoliosis (AIS) is the most common deformity of the spine, affecting 2-4% of the population. Previous studies have shown that the vertebrae in scoliotic spines undergo abnormal shape changes, however there has been little exploration of how scoliosis affects bone density distribution within the vertebrae. In this study, existing CT scans of 53 female idiopathic scoliosis patients with right-sided main thoracic curves were used to measure the lateral (right to left) bone density profile at mid-height through each vertebral body. Five key bone density profile measures were identified from each normalised bone density distribution, and multiple regression analysis was performed to explore the relationship between bone density distribution and patient demographics (age, height, weight, body mass index (BMI), skeletal maturity, time since Menarche, vertebral level, and scoliosis curve severity). Results showed a marked convex/concave asymmetry in bone density for vertebral levels at or near the apex of the scoliotic curve. At the apical vertebra, mean bone density at the left side (concave) cortical shell was 23.5% higher than for the right (convex) cortical shell, and cancellous bone density along the central 60% of the lateral path from convex to concave increased by 13.8%. The centre of mass of the bone density profile at the thoracic curve apex was located 53.8% of the distance along the lateral path, indicating a shift of nearly 4% toward the concavity of the deformity. These lateral bone density gradients tapered off when moving away from the apical vertebra. Multi-linear regressions showed that the right cortical shell peak bone density is significantly correlated with skeletal maturity, with each Risser increment corresponding to an increase in mineral equivalent bone density of 4-5%. There were also statistically significant relationships between patient height, weight and BMI, and the gradient of cancellous bone density along the central 60% of the lateral path. Bone density gradient is positively correlated with weight, and negatively correlated with height and BMI, such that at the apical vertebra, a unit decrease in BMI corresponds to an almost 100% increase in bone density gradient.

Mathematical modelling of muscle recruitment and function in the lumbar spine

Low back pain is an increasing problem in industrialised countries and although it is a major socio-economic problem in terms of medical costs and lost productivity, relatively little is known about the processes underlying the development of the condition. This is in part due to the complex interactions between bone, muscle, nerves and other soft tissues of the spine, and the fact that direct observation and/or measurement of the human spine is not possible using non-invasive techniques. Biomechanical models have been used extensively to estimate the forces and moments experienced by the spine. These models provide a means of estimating the internal parameters which can not be measured directly. However, application of most of the models currently available is restricted to tasks resembling those for which the model was designed due to the simplified representation of the anatomy. The aim of this research was to develop a biomechanical model to investigate the changes in forces and moments which are induced by muscle injury. In order to accurately simulate muscle injuries a detailed quasi-static three dimensional model representing the anatomy of the lumbar spine was developed. This model includes the nine major force generating muscles of the region (erector spinae, comprising the longissimus thoracis and iliocostalis lumborum; multifidus; quadratus lumborum; latissimus dorsi; transverse abdominis; internal oblique and external oblique), as well as the thoracolumbar fascia through which the transverse abdominis and parts of the internal oblique and latissimus dorsi muscles attach to the spine. The muscles included in the model have been represented using 170 muscle fascicles each having their own force generating characteristics and lines of action. Particular attention has been paid to ensuring the muscle lines of action are anatomically realistic, particularly for muscles which have broad attachments (e.g. internal and external obliques), muscles which attach to the spine via the thoracolumbar fascia (e.g. transverse abdominis), and muscles whose paths are altered by bony constraints such as the rib cage (e.g. iliocostalis lumborum pars thoracis and parts of the longissimus thoracis pars thoracis). In this endeavour, a separate sub-model which accounts for the shape of the torso by modelling it as a series of ellipses has been developed to model the lines of action of the oblique muscles. Likewise, a separate sub-model of the thoracolumbar fascia has also been developed which accounts for the middle and posterior layers of the fascia, and ensures that the line of action of the posterior layer is related to the size and shape of the erector spinae muscle. Published muscle activation data are used to enable the model to predict the maximum forces and moments that may be generated by the muscles. These predictions are validated against published experimental studies reporting maximum isometric moments for a variety of exertions. The model performs well for fiexion, extension and lateral bend exertions, but underpredicts the axial twist moments that may be developed. This discrepancy is most likely the result of differences between the experimental methodology and the modelled task. The application of the model is illustrated using examples of muscle injuries created by surgical procedures. The three examples used represent a posterior surgical approach to the spine, an anterior approach to the spine and uni-lateral total hip replacement surgery. Although the three examples simulate different muscle injuries, all demonstrate the production of significant asymmetrical moments and/or reduced joint compression following surgical intervention. This result has implications for patient rehabilitation and the potential for further injury to the spine. The development and application of the model has highlighted a number of areas where current knowledge is deficient. These include muscle activation levels for tasks in postures other than upright standing, changes in spinal kinematics following surgical procedures such as spinal fusion or fixation, and a general lack of understanding of how the body adjusts to muscle injuries with respect to muscle activation patterns and levels, rate of recovery from temporary injuries and compensatory actions by other muscles. Thus the comprehensive and innovative anatomical model which has been developed not only provides a tool to predict the forces and moments experienced by the intervertebral joints of the spine, but also highlights areas where further clinical research is required.

Oxygen consumption and muscle activation patterns during constant load exercise

The collective purpose of these two studies was to determine a link between the V02 slow component and the muscle activation patterns that occur during cycling. Six, male subjects performed an incremental cycle ergometer exercise test to determine asub-TvENT (i.e. 80% of TvENT) and supra-TvENT (TvENT + 0.75*(V02 max - TvENT) work load. These two constant work loads were subsequently performed on either three or four occasions for 8 mins each, with V02 captured on a breath-by-breath basis for every test, and EMO of eight major leg muscles collected on one occasion. EMG was collected for the first 10 s of every 30 s period, except for the very first 10 s period. The V02 data was interpolated, time aligned, averaged and smoothed for both intensities. Three models were then fitted to the V02 data to determine the kinetics responses. One of these models was mono-exponential, while the other two were biexponential. A second time delay parameter was the only difference between the two bi-exponential models. An F-test was used to determine significance between the biexponential models using the residual sum of squares term for each model. EMO was integrated to obtain one value for each 10 s period, per muscle. The EMG data was analysed by a two-way repeated measures ANOV A. A correlation was also used to determine significance between V02 and IEMG. The V02 data during the sub-TvENT intensity was best described by a mono-exponential response. In contrast, during supra-TvENT exercise the two bi-exponential models best described the V02 data. The resultant F-test revealed no significant difference between the two models and therefore demonstrated that the slow component was not delayed relative to the onset of the primary component. Furthermore, only two parameters were deemed to be significantly different based upon the two models. This is in contrast to other findings. The EMG data, for most muscles, appeared to follow the same pattern as V02 during both intensities of exercise. On most occasions, the correlation coefficient demonstrated significance. Although some muscles demonstrated the same relative increase in IEMO based upon increases in intensity and duration, it cannot be assumed that these muscles increase their contribution to V02 in a similar fashion. Larger muscles with a higher percentage of type II muscle fibres would have a larger increase in V02 over the same increase in intensity.

Application of micro CT and computation modeling in bone tissue engineering

Computer aided technologies, medical imaging, and rapid prototyping has created new possibilities in biomedical engineering. The systematic variation of scaffold architecture as well as the mineralization inside a scaffold/bone construct can be studied using computer imaging technology and CAD/CAM and micro computed tomography (CT). In this paper, the potential of combining these technologies has been exploited in the study of scaffolds and osteochondral repair. Porosity, surface area per unit volume and the degree of interconnectivity were evaluated through imaging and computer aided manipulation of the scaffold scan data. For the osteochondral model, the spatial distribution and the degree of bone regeneration were evaluated. In this study the versatility of two softwares Mimics (Materialize), CTan and 3D realistic visualization (Skyscan) were assessed, too.

Clonal characterization of bone marrow derived stem cells and their application for bone regeneration

Tissue engineering allows the design of functionally active cells within supportive bio-scaffolds to promote the development of new tissues such as cartilage and bone for the restoration of pathologically altered tissues. However, all bone tissue engineering applications are limited by a shortage of stem cells. The adult bone marrow stroma contains a subset of nonhematopoietic cells referred to as bone marrow mesenchymal stem cells (BMSCs). BMSCs are of interest because they are easily isolated from a small aspirate of bone marrow and readily generate single- cell-derived colonies. These cells have the capacity to undergo extensive replication in an undifferentiated state ex vivo. In addition, BMSCs have the potential to develop either in vitro or in vivo into distinct mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Thus, BMSCs are an attractive cell source for tissue engineering approaches. However, BMSCs are not homo- geneous and the quantity of stem cells decreases in the bone marrow in aged population. A sequential loss of lineage differentiation potential has been found in the mixed culture of bone marrow stromal cells due to a heterogenous popu- lation. Therefore, a number of studies have proposed that homogenous bone marrow stem cells can be generated from clonal culture of bone marrow cells and that BMSC clones have the greatest potential for the application of bone regeneration in vivo

The effects of muscle fatigue on knee function during landing

The human knee acts as a sophisticated shock absorber during landing movements. The ability of the knee to perform this function in the real world is remarkable given that the context of the landing movement may vary widely between performances. For this reason, humans must be capable of rapidly adjusting the mechanical properties of the knee under impact load in order to satisfy many competing demands. However, the processes involved in regulating these properties in response to changing constraints remain poorly understood. In particular, the effects of muscle fatigue on knee function during step landing are yet to be fully explored. Fatigue of the knee muscles is significant for 2 reasons. First, it is thought to have detrimental effects on the ability of the knee to act as a shock absorber and is considered a risk factor for knee injury. Second, fatigue of knee muscles provides a unique opportunity to examine the mechanisms by which healthy individuals alter knee function. A review of the literature revealed that the effect of fatigue on knee function during landing has been assessed by comparing pre and postfatigue measurements, with fatigue induced by a voluntary exercise protocol. The information is limited by inconsistent results with key measures, such as knee stiffness, showing varying results following fatigue, including increased stiffness, decreased stiffness or failure to detect any change in some experiments. Further consideration of the literature questions the validity of the models used to induce and measure fatigue, as well as the pre-post study design, which may explain the lack of consensus in the results. These limitations cast doubt on the usefulness of the available information and identify a need to investigate alternative approaches. Based on the results of this review, the aims of this thesis were to: • evaluate the methodological procedures used in validation of a fatigue model • investigate the adaptation and regulation of post-impact knee mechanics during repeated step landings • use this new information to test the effects of fatigue on knee function during a step-landing task. To address the aims of the thesis, 3 related experiments were conducted that collected kinetic, kinematic and electromyographic data from 3 separate samples of healthy male participants. The methodologies involved optoelectronic motion capture (VICON), isokinetic dynamometry (System3 Pro, BIODEX) and wireless surface electromyography (Zerowire, Aurion, Italy). Fatigue indicators and knee function measures used in each experiment were derived from the data. Study 1 compared the validity and reliability of repetitive stepping and isokinetic contractions with respect to fatigue of the quadriceps and hamstrings. Fifteen participants performed 50 repetitions of each exercise twice in randomised order, over 4 sessions. Sessions were separated by a minimum of 1 week’s rest, to ensure full recovery. Validity and reliability depended on a complex interaction between the exercise protocol, the fatigue indicator, the individual and the muscle of interest. Nevertheless, differences between exercise protocols indicated that stepping was less effective in eliciting valid and reliable changes in peak power and spectral compression, compared with isokinetic exercise. A key finding was that fatigue progressed in a biphasic pattern during both exercises. The point separating the 2 phases, known as the transition point, demonstrated superior between-test reliability during the isokinetic protocol, compared with stepping. However, a correction factor should be used to accurately apply this technique to the study of fatigue during landing. Study 2 examined alterations in knee function during repeated landings, with a different sample (N =12) performing 60 consecutive step landing trials. Each landing trial was separated by 1-minute rest periods. The results provided new information in relation to the pre-post study design in the context of detecting adjustments in knee function during landing. First, participants significantly increased or decreased pre-impact muscle activity or post-impact mechanics despite environmental and task constraints remaining unchanged. This is the 1st study to demonstrate this effect in healthy individuals without external feedback on performance. Second, single-subject analysis was more effective in detecting alterations in knee function compared to group-level analysis. Finally, repeated landing trials did not reduce inter-trial variability of knee function in some participants, contrary to assumptions underpinning previous studies. The results of studies 1 and 2 were used to modify the design of Study 3 relative to previous research. These alterations included a modified isokinetic fatigue protocol, multiple pre-fatigue measurements and singlesubject analysis to detect fatigue-related changes in knee function. The study design incorporated new analytical approaches to investigate fatiguerelated alterations in knee function during landing. Participants (N = 16) were measured during multiple pre-fatigue baseline trial blocks prior to the fatigue model. A final block of landing trials was recorded once the participant met the operational fatigue definition that was identified in Study 1. The analysis revealed that the effects of fatigue in this context are heavily dependent on the compensatory response of the individual. A continuum of responses was observed within the sample for each knee function measure. Overall, preimpact preparation and post-impact mechanics of the knee were altered with highly individualised patterns. Moreover, participants used a range of active or passive pre-impact strategies to adapt post-impact mechanics in response to quadriceps fatigue. The unique patterns identified in the data represented an optimisation of knee function based on priorities of the individual. The findings of these studies explain the lack of consensus within the literature regarding the effects of fatigue on knee function during landing. First, functional fatigue protocols lack validity in inducing fatigue-related changes in mechanical output and spectral compression of surface electromyography (sEMG) signals, compared with isokinetic exercise. Second, fatigue-related changes in knee function during landing are confounded by inter-individual variation, which limits the sensitivity of group-level analysis. By addressing these limitations, the 3rd study demonstrated the efficacies of new experimental and analytical approaches to observe fatigue-related alterations in knee function during landing. Consequently, this thesis provides new perspectives into the effects of fatigue in knee function during landing. In conclusion: • The effects of fatigue on knee function during landing depend on the response of the individual, with considerable variation present between study participants, despite similar physical characteristics. • In healthy males, adaptation of pre-impact muscle activity and postimpact knee mechanics is unique to the individual and reflects their own optimisation of demands such as energy expenditure, joint stability, sensory information and loading of knee structures. • The results of these studies should guide future exploration of adaptations in knee function to fatigue. However, research in this area should continue with reduced emphasis on the directional response of the population and a greater focus on individual adaptations of knee function.

Biceps brachii muscle oxygenation in electrical muscle stimulation

The purpose of this study was to compare between electrical muscle stimulation (EMS) and maximal voluntary (VOL) isometric contractions of the elbow flexors for changes in biceps brachii muscle oxygenation (tissue oxygenation index, TOI) and haemodynamics (total haemoglobin volume, tHb = oxygenated-Hb + deoxygenated-Hb) determined by near-infrared spectroscopy (NIRS). The biceps brachii muscle of 10 healthy men (23–39 years) was electrically stimulated at high frequency (75 Hz) via surface electrodes to evoke 50 intermittent (4-s contraction, 15-s relaxation) isometric contractions at maximum tolerated current level (EMS session). The contralateral arm performed 50 intermittent (4-s contraction, 15-s relaxation) maximal voluntary isometric contractions (VOL session) in a counterbalanced order separated by 2–3 weeks. Results indicated that although the torque produced during EMS was approximately 50% of VOL (P<0Æ05), there was no significant difference in the changes in TOI amplitude or TOI slope between EMS and VOL over the 50 contractions. However, the TOI amplitude divided by peak torque was approximately 50% lower for EMS than VOL (P<0Æ05), which indicates EMS was less efficient than VOL. This seems likely because of the difference in the muscles involved in the force production between conditions. Mean decrease in tHb amplitude during the contraction phases was significantly (P<0Æ05) greater for EMS than VOL from the 10th contraction onwards, suggesting that the muscle blood volume was lower in EMS than VOL. It is concluded that local oxygen demand of the biceps brachii sampled by NIRS is similar between VOL and EMS.