Collagen-I influences the post-translational regulation, binding partners and role of Annexin A2 in breast cancer progression.

Introduction: The extracellular matrix (ECM) has been heavily implicated in the development and progression of cancer. We have previously shown that Annexin A2 is integral in the migration and invasion of breast cancer cells and in the clinical progression of ER-negative breast cancer, processes which are highly influenced by the surrounding tumor microenvironment and ECM. Methods: We investigated how modulations of the ECM may affect the role of Annexin A2 in MDA-MB-231 breast cancer cells using western blotting, immunofluorescent confocal microscopy and immuno-precipitation mass spectrometry techniques. Results: We have shown that the presence of collagen-I, the main constituent of the ECM, increases the post-translational phosphorylation of Annexin A2 and subsequently causes the translocation of Annexin A2 to the extracellular surface. In the presence of collagen-I, we identified fibronectin as a novel interactor of Annexin A2, using mass spectrometry analysis. We then demonstrated that reducing Annexin A2 expression decreases the degradation of fibronectin by cancer cells and this effect on fibronectin turnover is increased according to collagen-I abundance. Discussion: Our results suggest that Annexin A2's role in promoting cancer progression is mediated by collagen-I and Annexin A2 maybe a therapeutic target in the bi-directional cross-talk between cancer cells and ECM remodeling that supports metastatic cancer progression.

The effectiveness of community dance in people with cancer: a mixed-methods systematic review and meta-analysis.

There is a need for both feasible and enjoyable physical activity programmes for people on a cancer journey. Emerging evidence suggests that dance can have a positive effect on health and well-being in this cohort. We aimed to synthesize the quantitative and qualitative literature exploring the effectiveness and impact of community dance interventions in people with all types and stages of cancer. A systematic search was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in Pubmed, EMBASE, Medline Ovid, CINAHL and PEDro databases. Quantitative and qualitative data were extracted and synthesized using a convergent segregated approach. The numeric data were analysed using descriptive statistics, narrative synthesis and meta-analysis where possible. The qualitative data were analysed using thematic analysis. The Downs and Black critical appraisal tool and the Critical Appraisal Skills Programme were used to assess the quality of the quantitative and qualitative literature, respectively. Eighteen studies were included in this mixed-methods review with seven trials included in the meta-analysis. Statistically significant improvements were found in favour of community dance for functional capacity, fatigue, quality-of-life and depression in comparison to no intervention. Evidence suggests dance is a safe and feasible form of physical activity both during and after cancer treatment. Participants reported good social support, education regarding physical activity and local access as key facilitators to participation. We concluded that dance is a feasible and enjoyable intervention for many people with various forms of cancer. Community dance programmes can improve both physical and psychological outcomes in people on a cancer journey.

Mechanical and morphological characterisation of porcine urethras for the assessment of paediatric urinary catheter safety.

Paediatric urinary catheters are often necessary in critical care settings or to address congenital anomalies affecting the urogenital system. Iatrogenic injuries can occur during the placement of such catheters, highlighting the need for a safety device that can function in paediatric settings. Despite successful efforts to develop devices that improve the safety of adult urinary catheters, no such devices are available for use with paediatric catheters. This study investigates the potential for utilising a pressure-controlled safety mechanism to limit the trauma experienced by paediatric patients during inadvertent inflation of a urinary catheter anchoring balloon in the urethra. Firstly, we establish a paediatric model of the human urethra using porcine tissue by characterising the mechanical and morphological properties of porcine tissue at increasing postnatal timepoints (8, 12, 16 and 30 weeks). We identified that porcine urethras harvested from pigs at postnatal week 8 and 12 exhibit morphological properties (diameter and thickness) that are statistically distinct from adult porcine urethras (postnatal week 30). We therefore utilise urethra tissue from postnatal week 8 and 12 pigs as a model to evaluate a pressure-controlled approach to paediatric urinary catheter balloon inflation intended to limit tissue trauma during inadvertent inflation in the urethra. Our results show that limiting catheter system pressure to 150 kPa avoided trauma in all tissue samples. Conversely, all of the tissue samples that underwent traditional uncontrolled urinary catheter inflation experienced complete rupture. The findings of this study pave the way for the development of a safety device for use with paediatric catheters, thereby alleviating the burden of catastrophic trauma and life changing injuries in children due to a preventable iatrogenic urogenital event.

The Effect of Unilateral Versus Bilateral Strength Training on Isometric-Squat Peak Force and Interlimb Asymmetry in Young, Recreationally Strength-Trained Men.

PURPOSE: To compare the effects of bilateral strength training (BLST) versus unilateral strength training (ULST) on changes in peak force (PF) and interlimb asymmetry (ILA) in the isometric squat at a 120° knee angle (ISq120). METHOD: A total of 31 young, recreationally strength-trained men performed either BLST (n = 18) or ULST (n = 13), twice per week for 6 weeks. The total number of repetitions, duty cycle, and effort were standardized between training groups (ie, differing only in the exercises performed). Changes in PF and ILA were assessed pretraining and posttraining. RESULTS: Comparable increases in PF were observed in the BLST group (mean [SD] change; 17.4% [20.5%], P = .001, standardized mean difference [SMD] = 0.45) and the ULST group (11.4% [19.1%], P = .042, SMD = 0.25). No significant changes in symmetry index (SI) scores were observed following BLST (mean [SD] change; 0 [5.7], P = .526, SMD = -0.12) or ULST (+3 [6.0], P = .702, SMD = 0.4). Individual analyses of subjects with marked ILA (ie, baseline SI score > baseline coefficient of variation) revealed a trend toward BLST being more effective at attenuating SI scores in the ISq120. CONCLUSIONS: Overall, both BLST and ULST are effective for increasing ISq120 PF. However, it appears that BLST may be more effective at reducing SI scores in those with marked ILA.

Comparison of macroscale and microscale mechanical properties of fresh and fixed-frozen porcine colonic tissue.

Mechanical changes to the microenvironment of the extracellular matrix (ECM) in tissue have been hypothesised to elicit a pathogenic response in the surrounding cells. Hence, 3D scaffolds are a popular method of studying cellular behaviour under conditions that mimic in vivo microenvironment. To create a 3D biomimetic scaffold that captures the in vivo ECM microenvironment a robust mechanical characterisation of the whole ECM at the microscale is necessary. This study examined the multiscale methods of characterising the ECM microenvironment using porcine colon tissue. To facilitate fresh tissue microscale mechanical characterisation, a protocol for sectioning fresh, unfixed, soft biological tissue was developed. Four experiments examined both the microscale and macroscale mechanics of both fresh (Fr) and fixed-frozen (FF) porcine colonic tissue using microindentation for microscale testing and uniaxial compression testing for macroscale testing. The results obtained in this study show a significant difference in elastic modulus between Fr and FF tissue at both the macroscale and microscale. There was an order of magnitude difference between the Fr and FF tissue at the microscale between each of the three layers of the colon tested i.e. the muscularis propria (MP), the submucosa (SM) and the mucosa (M). Macroscale testing cannot capture these regional differences. The findings in this study suggest that the most appropriate method for mechanically characterising the ECM is fresh microscale mechanical microindentation. These methods can be used on a range of biological tissues to create 3D biomimetic scaffolds that are more representative of the in vivo ECM, allowing for a more in-depth characterisation of the disease process.

The Influence of Maximal Strength and Knee Angle on the Reliability of Peak Force in the Isometric Squat.

This study aimed to investigate the test-retest reliability of peak force in the isometric squat across the strength spectrum using coefficient of variation (CV) and intra-class correlation coefficient (ICC). On two separate days, 59 healthy men (mean (SD) age 23.0 (4.1) years; height 1.79 (0.7) m; body mass 84.0 (15.2) kg) performed three maximal effort isometric squats in two positions (at a 120° and a 90° knee angle). Acceptable reliability was observed at both the 120° (CV = 7.5 (6.7), ICC = 0.960 [0.933, 0.977]) and 90° positions (CV = 9.2 (8.8), ICC = 0.920 [0.865, 0.953]). There was no relationship between peak force in the isometric squat and the test-retest reliability at either the 120° (r = 0.052, p = 0.327) or 90° (r = 0.014, p = 0.613) positions. A subgroup of subjects (n = 17) also completed the isometric squat test at a 65° knee angle. Acceptable reliability was observed in this position (CV = 9.6 (9.3), ICC = 0.916 [0.766, 0.970]) and reliability was comparable to the 120° and 90° positions. Therefore, we deem isometric squat peak force output to be a valid and reliable measure across the strength spectrum and in different isometric squat positions.

Sex-related differences in joint-angle-specific hamstring-to-quadriceps function following fatigue.

The purpose of this study was to examine the effect of fatiguing exercise on sex-related differences in the function of hamstring and quadriceps muscles at several angular velocities and joint angles. Physically active participants (50 male: 28.7 ± 4.5y, 1.82 ± 0.07 m, 82.3 ± 6.87 kg; 50 female: 27.0 ± 5.8y, 1.61 ± 0.08 m, 68.75 ± 9.24 kg) carried out an isokinetic assessment to determine concentric and eccentric torques during knee extension and flexion actions at three different angular velocities (60/180/300°/s). The H/QFUNCT was calculated using peak torque (PT) values at 3 different joint-angle-specific (15°, 30° and 45° of knee flexion). A repeated measures analysis of variance (ANOVA) was used to compare within group results. Between group comparisons of sex-related differences were assessed by independent T-tests. Fatiguing exercise in males resulted in a decrease in H/QFUNCT ratios for each angle of knee flexion at both 60°/s and 300°/s angular velocities (p < 0.05). In females, significant decreases in H/QFUNCT ratios were observed following fatiguing exercise for each angle of knee flexion and angular velocity (p < 0.01). Significant differences in H/QFUNCT ratios following fatiguing exercise were evident between males and females at each joint angle and angular velocity (p < 0.01). These findings indicate sex related differences in H/QFUNCT ratios following fatiguing exercise. Females have greater reductions in torque and H/QFUNCT ratios following fatigue than their male counterparts. This potentially exposes females to higher risks of injury, particularly when fatigued. Practitioners should attend to the imbalance in fatigue resistance of hamstring and quadriceps function, particularly in female athletes.