Differential calcineurin signalling activity and regeneration efficacy in diaphragm and limb muscles of dystrophic mdx mice

Calcineurin activity is essential for successful skeletal muscle regeneration in young mdx mice and in wild type mice following myotoxic injury and cryodamage. In mature myofibres of adult mdx mice, calcineurin stimulation can ameliorate the dystrophic pathology. The aim of this study was to test the hypothesis that the more severe dystrophic pathology of the diaphragm compared with hindlimb muscles of mdx mice could be attributed to aberrant calcineurin signalling and that due to ongoing regeneration calcineurin activity would be greater in muscles of adult mdx than wild type mice. Differences in markers of regeneration between tibialis anterior and diaphragm muscles were also characterised, to determine whether there was an association between regeneration efficacy and calcineurin activity in dystrophic muscles. In diaphragm muscles of adult mdx mice, the proportion of centrally nucleated fibres and developmental myosin heavy chain protein expression was lower and myogenin protein expression was higher than in tibialis anterior muscles. Calcineurin and activated NFATc1 protein content and calcineurin phosphatase activity were higher in muscles from mdx than wild type mice and calcineurin activation was greater in diaphragm than tibialis anterior muscles of mdx mice. Thus, despite greater calcineurin activity in diaphragm compared to hindlimb muscles, regeneration events downstream of myoblast differentiation and mediated by the injured myofibre were severely compromised.

The contribution of upper limb and total body movement to adolescents’ energy expenditure whilst playing Nintendo Wii

Little research documents the contribution of upper limb and total body movement to energy expenditure (EE) during active video gaming. To address this, EE, heart rate (HR), and, upper limb and total body movement were assessed in 11- to 17-year-old adolescents whilst playing three active (Nintendo Wii) and one sedentary (XBOX 360) video games. Non-dominant upper limb activity, EE and HR were significantly greater during Wii Sports boxing [mean 267.2 (SD 115.8) J kg−1 min−1; 136.7 (24.5) beats min−1] than tennis or bowling (P ≤ 0.044). For all active games hip activity best predicted EE (R 2 ≥ 0.53), with two-measure models of HR and single-site activity data, and multi-site activity data, similarly explaining the variance in EE (R 2 ≥ 0.64). The physiological cost of upper-body orientated active video games increased when movement of both upper limbs was encouraged. Improvements in EE explanatory power provide support for multi-site activity monitoring during unique, non-ambulatory activities.

Strength training of one limb increases corticomotor excitability projecting to the contralateral homologous limb

The contralateral transfer of strength following unilateral strength training (ULS) is thought to be due to changes within the nervous system. Using transcranial magnetic stimulation (TMS) we compared corticospinal responses following ULS of the right biceps brachii (BB) projecting to the untrained left BB. Motor evoked potentials (MEPs) were recorded from both BB of 23 individuals pre and post 4 weeks heavy load (80% of 1RM) ULS of right BB. TMS was delivered at intensities below active motor threshold (AMT) to saturation of the MEP (MEP_max). ULS resulted in a 28% increase in 1RM right BB strength, resulting in a 19.2% increase in contralateral strength of the left BB (p = .0001). There was a significant increase in MEP amplitude of 30.3% (p = .03), 33% (p = .05), and 26.5% (p = .01) at AMT, 20% above AMT and MEP_max respectively. No significant differences in silent period were seen at AMT, 20% above AMT or MEP_max. This study has demonstrated increased corticospinal excitability projecting to the untrained arm following heavy load ULS.

Reduction in corticospinal inhibition in the trained and untrained limb following unilateral leg strength training

This study used transcranial magnetic stimulation to measure the corticospinal responses following 8 weeks of unilateral leg strength training. Eighteen healthy, non-strength trained participants (14 male, 4 female; 18–35 years of age) were matched for age, gender, and pre-training strength; and assigned to a training or control group. The trained group participated in unilateral horizontal leg press strength training, progressively overloaded and wave periodised, thrice per week for 8 weeks. Testing occurred prior to the intervention, at the end of 4 weeks and at the completion of training at 8 weeks. Participants were tested in both legs for one repetition maximum strength, muscle thickness, maximal electromyography (EMG) activity, and corticospinal excitability and inhibition. No changes were observed in muscle thickness in either leg. The trained leg showed an increase in strength of 21.2% (P = 0.001) and 29.0% (P = 0.007, compared to pre-testing) whilst the untrained contralateral leg showed 17.4% (P = 0.01) and 20.4% (P = 0.004, compared to pre-testing) increases in strength at 4 and 8 weeks, respectively. EMG and corticospinal excitability did not change; however, corticospinal inhibition was significantly reduced by 17.7 ms (P = 0.003) and 17.3 ms (P = 0.001) at 4 and 8 weeks, respectively, in the trained leg, and 25.1 ms (P = 0.001) and 20.8 ms (P = 0.001) at 4 and 8 weeks, respectively, in the contralateral untrained leg. This data support the theory of corticospinal adaptations underpinning cross-education gains in the lower limbs following unilateral strength training.

Contribution of fibroblast and mast cell (afferent) and tumor (efferent) IL-6 effects within the tumor microenvironment

Hyperactive inflammatory responses following cancer initiation have led to cancer being described as a ‘wound that never heals’. These inflammatory responses elicit signals via NFκB leading to IL-6 production, and IL-6 in turn has been shown to induce epithelial to mesenchymal transition in breast cancer cells in vitro, implicating a role for this cytokine in cancer cell invasion. We previously have shown that conditioned medium derived from cancer-associated fibroblasts induced an Epithelial to Mesenchymal transition (EMT) in PMC42-LA breast cancer cells and we have now identify IL-6 as present in this medium. We further show that IL-6 is expressed approximately 100 fold higher in a cancer-associated fibroblast line compared to normal fibroblasts. Comparison of mouse-specific (stroma) and human-specific (tumor) IL-6 mRNA expression from MCF-7, MDA MB 468 and MDA MB 231 xenografts also indicated the stroma rather than tumor as a significantly higher source of IL-6 expression. Mast cells (MCs) feature in inflammatory cancer-associated stroma, and activated MCs secrete IL-6. We observed a higher MC index (average number of mast cells per xenograft section/average tumor size) in MDA MB 468 compared to MDA MB 231 xenografts, where all MC were observed to be active (degranulating). This higher MC index correlated with greater mouse-specific IL-6 expression in the MDA MB 468 xenografts, implicating MC as an important source of stromal IL-6. Furthermore, immunohistochemistry on these xenografts for pSTAT3, which lies downstream of the IL-6 receptor indicated frequent correlations between pSTAT3 and mast cell positive cells. Analysis of publically available databases for IL-6 expression in patient tissue revealed higher IL-6 in laser capture microdissected stroma compared to adjacent tissue epithelium from patients with inflammatory breast cancer (IBC) and invasive non-inflammatory breast cancer (non-IBC) and we show that IL-6 expression was significantly higher in Basal versus Luminal molecular/phenotypic groupings of breast cancer cell lines. Finally, we discuss how afferent and efferent IL-6 pathways may participate in a positive feedback cycle to dictate tumor progression.

Is there a link between motor performance variability and social-communicative impairment in children with ADHD-CT : a kinematic study using an upper limb Fitts’ aiming task

 Objective: This study investigated the relationship between motor performance and social-communicative impairment in children with ADHD-combined type (ADHD-CT). Method: An upper limb Fitts’ aiming task was used as a measure of motor performance and the Social Responsiveness Scale as a measure of social-communicative/autistic impairment in the following groups: ADHD-CT (n = 11) and typically developing (TD) controls (n = 10). Results: Children with ADHD-CT displayed greater variability in their movements, reflected in increased error variance over repeated aiming trials compared with TD controls. Motor performance variability was associated with social-communicative deficits in the ADHD-CT but not in the TD group. Conclusion: Social-communicative impairments further complicate the clinical picture of ADHD-CT; therefore, further research in this area is warranted to ascertain whether a particular pattern of motor disturbance in children with ADHD-CT may be clinically useful in identifying and assessing children with a more complex ADHD presentation. © 2012 SAGE Publications.

Relationship between lower limb neuromuscular performanceand bone strength in postmenopausal women with mild knee osteoarthritis

Objectives: To investigate whether neuromuscular performance predicts lower limb bone strength in different lower limb sites in postmenopausal women with mild knee osteoarthritis (OA). Methods: Neuromuscular performance of 139 volunteer women aged 50-68 with mild knee OA was measured using maximal counter movement jump test, isometric knee flexion and extension force and figure-of-eight-running test. Femoral neck section modulus (Z, mm3) was determined by data obtained from dualenergy X-ray absorptiometry. Data obtained using peripheral quantitative computed tomography was used to asses distal tibia compressive (BSId, g2/cm4) and tibial mid-shaft bending (SSImaxmid, mm3) strength indices. Results: After adjustment for height, weight and age, counter movement jump peak power production was the strongest independent predictor for Z (β=0.44; p<0.001) and for BSId (β=0.32; p=0.003). This was also true in concentric net impulse for Z (β=0.37; p=0.001) and for BSId (β=0.40; p<0.001). Additionally, knee extension force (β=0.30; p<0.001) and figure-of-eight-running test (β= -0.32; p<0.001) were among strongest independent predictors for BSId after adjustments. For SSImaxmid, concentric net impulse (β=0.33; p=0.002) remained as the strongest independent predictor after adjustments. Conclusions: Neuromuscular performance in postmenopausal women with mild knee OA predicted lower limb bone strength in every measured skeletal site.

Efficacy comparison of clustering systems for limb detection

This paper presents a comparison of applying different clustering algorithms on a point cloud constructed from the depth maps captured by a RGBD camera such as Microsoft Kinect. The depth sensor is capable of returning images, where each pixel represents the distance to its corresponding point not the RGB data. This is considered as the real novelty of the RGBD camera in computer vision compared to the common video-based and stereo-based products. Depth sensors captures depth data without using markers, 2D to 3D-transition or determining feature points. The captured depth map then cluster the 3D depth points into different clusters to determine the different limbs of the human-body. The 3D points clustering is achieved by different clustering techniques. Our Experiments show good performance and results in using clustering to determine different human-body limbs.