914 resultados para cross-functional teams


Relevância:

40.00% 40.00%

Publicador:

Resumo:

STUDY DESIGN: Clinical measurement. OBJECTIVE: To translate and culturally adapt the Lower Extremity Functional Scale (LEFS) into a Brazilian Portuguese version, and to test the construct and content validity and reliability of this version in patients with knee injuries. BACKGROUND: There is no Brazilian Portuguese version of an instrument to assess the function of the lower extremity after orthopaedic injury. METHODS: The translation of the original English version of the LEFS into a Brazilian Portuguese version was accomplished using standard guidelines and tested in 31 patients with knee injuries. Subsequently, 87 patients with a variety of knee disorders completed the Brazilian Portuguese LEES, the Medical Outcomes Study 36-Item Short-Form Health Survey, the Western Ontario and McMaster Universities Osteoarthritis Index, and the International Knee Documentation Committee Subjective Knee Evaluation Form and a visual analog scale for pain. All patients were retested within 2 days to determine reliability of these measures. Validation was assessed by determining the level of association between the Brazilian Portuguese LEFS and the other outcome measures. Reliability was documented by calculating internal consistency, test-retest reliability, and standard error of measurement. RESULTS: The Brazilian Portuguese LEES had a high level of association with the physical component of the Medical Outcomes Study 36-Item Short-Form Health Survey (r = 0.82), the Western Ontario and McMaster Universities Osteoarthritis Index (r = 0.87), the International Knee Documentation Committee Subjective Knee Evaluation Form (r = 0.82), and the pain visual analog scale (r = -0.60) (all, P<.05). The Brazilian Portuguese LEES had a low level of association with the mental component of the Medical Outcomes Study 36-Item Short-Form Health Survey (r = 0.38, P<.05). The internal consistency (Cronbach alpha = .952) and test-retest reliability (intraclass correlation coefficient = 0.957) of the Brazilian Portuguese version of the LEES were high. The standard error of measurement was low (3.6) and the agreement was considered high, demonstrated by the small differences between test and retest and the narrow limit of agreement, as observed in Bland-Altman and survival-agreement plots. CONCLUSION: The translation of the LEFS into a Brazilian Portuguese version was successful in preserving the semantic and measurement properties of the original version and was shown to be valid and reliable in a Brazilian population with knee injuries. J Ort hop Sports Phys Ther 2012;42(11):932-939, Epub 9 October 2012. doi:10.2519/jospt.2012.4101

Relevância:

40.00% 40.00%

Publicador:

Resumo:

Hepatitis C virus (HCV) clearance has been associated with reduced viral evolution in targeted cytotoxic T-lymphocyte (CTL) epitopes, suggesting that HCV clearers may mount CTL responses with a superior ability to recognize epitope variants and prevent viral immune escape. Here, 40 HCV-infected subjects were tested with 406 10-mer peptides covering the vast majority of the sequence diversity spanning a 197-residue region of the NS3 protein. HCV clearers mounted significantly broader CTL responses of higher functional avidity and with wider variant cross-recognition capacity than nonclearers. These observations have important implications for vaccine approaches that may need to induce high-avidity responses in vivo.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The purpose of this study was to characterise the functional outcome of 12 transfemoral amputees fitted with osseointegrated fixation using temporal gait characteristics. The objectives were (A) to present the cadence, duration of gait cycle, support and swing phases with an emphasis on the stride-to-stride and participant-to-participant variability, and (B) to compare these temporal variables with normative data extracted from the literature focusing on transfemoral amputees fitted with a socket and able-bodied participants. The temporal variables were extracted from the load applied on the residuum during straight level walking, which was collected at 200 Hz by a transducer. A total of 613 strides were assessed. The cadence (46±4 strides/min), the duration of the gait cycle (1.29±0.11 s), support (0.73±0.07 s, 57±3% of CG) and swing (0.56±0.07 s, 43±3% of GC) phases of the participants were 2% quicker, 3%, 6% shorter and 1% longer than transfemoral amputees using a socket as well as 11% slower, 9%, 6% and 13% longer than able-bodied, respectively. All combined, the results indicated that the fitting of an osseointegrated fixation has enabled this group of amputees to restore their locomotion with a highly functional level. Further longitudinal and cross-sectional studies would be required to confirm these outcomes. Nonetheless, the data presented can be used as benchmark for future comparisons. It can also be used as input in generic algorithms using templates of patterns of loading to recognise activities of daily living and to detect falls.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Communication is one team process factor that has received considerable research attention in the team literature. This literature provides equivocal evidence regarding the role of communication in team performance and yet, does not provide any evidence for when communication becomes important for team performance. This research program sought to address this evidence gap by a) testing task complexity and team member diversity (race diversity, gender diversity and work value diversity) as moderators of the team communication — performance relationship; and b) testing a team communication — performance model using established teams across two different task types. The functional perspective was used as the theoretical framework for operationalizing team communication activity. The research program utilised a quasi-experimental research design with participants from a large multi-national information technology company whose Head Office was based in Sydney, Australia. Participants voluntarily completed two team building exercises (a decision making and production task), and completed two online questionnaires. In total, data were collected from 1039 individuals who constituted 203 work teams. Analysis of the data revealed a small number of significant moderation effects, not all in the expected direction. However, an interesting and unexpected finding also emerged from Study One. Large and significant correlations between communication activity ratings were found across tasks, but not within tasks. This finding suggested that teams were displaying very similar profiles of communication on each task, despite the tasks having different communication requirements. Given this finding, Study Two sought to a) determine the relative importance of task versus team effects in explaining variance in team communication measures for established teams; b) determine if established teams had reliable and discernable team communication profiles and if so, c) investigate whether team communication profiles related to task performance. Multi-level modeling and repeated measures analysis of variance (ANOVA) revealed that task type did not have an effect on team communication ratings. However, teams accounted for 24% of the total variance in communication measures. Through cluster analysis, five reliable and distinct team communication profiles were identified. Consistent with the findings of the multi-level analysis and repeated measures ANOVA, teams’ profiles were virtually identical across the decision making and production tasks. A relationship between communication profile and performance was identified for the production task, although not for the decision making task. This research responds to calls in the literature for a better understanding of when communication becomes important for team performance. The moderators tested in this research were not found to have a substantive or reliable effect on the relationship between communication and performance. However, the consistency in team communication activity suggests that established teams can be characterized by their communication profiles and further, that these communication profiles may have implications for team performance. The findings of this research provide theoretical support for the functional perspective in terms of the communication – performance relationship and further support the team development literature as an explanation for the stability in team communication profiles. This research can also assist organizations to better understand the specific types of communication activity and profiles of communication that could offer teams a performance advantage.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Since 2005 QUT through a number of large Teaching and Learning Grants has sponsored a range of teamwork learning initiatives to assist students to develop the teamwork skills demanded by industry. After a suite of six online team learning modules was developed, first year unit coordinators requested an additional module to address the challenges of working with the diverse range of social, cultural and personal values that students from different backgrounds bring to student teams. The Intercultural Teams module asks students to map themselves against a Cultural Orientations Framework so they can understand their own cultural beliefs. By learning about other cultural orientations and comparing and analysing their effects, team members can develop communication and team process management strategies to leverage their differences to realise effective and creative outcomes. The interactive session will demonstrate the elements of the Intercultural Teams module and ask participants to consider ways the module can be integrated into classroom learning to support the development of students’ intercultural competencies.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Visual impairment is an important contributing factor in falls among older adults, which is one of the leading causes of injury and injury-related death in this population. Visual impairment is also associated with greater disability among older adults, including poorer health-related quality of life, increased frailty and reduced postural stability. The majority of this evidence, however, is based on measures of central visual function, rather than peripheral visual function. As such, there is comparatively limited research on the associations between peripheral visual function, disability and falls, and even fewer studies involving older adults with specific diseases which affect peripheral visual function, the most common of which is glaucoma. Glaucoma is one of the leading causes of irreversible vision loss among older adults, affecting around 3 per cent of adults aged over 60 years. The condition is characterised by retinal nerve fibre loss, primarily affecting peripheral visual function. Importantly, the number of older adults with glaucomatous visual impairment is projected to increase as the ageing population grows. The first component of the thesis examined the cross-sectional association between glaucomatous visual impairment and health-related quality of life (Study 1a), functional status (Study 1b) and postural stability (Study 1c) among older adults. A cohort of 74 community-dwelling adults with glaucoma (mean age 74.2 ± 5.9 years) was recruited and completed a baseline assessment. A number of visual function measures was assessed, including central visual function (visual acuity and contrast sensitivity), motion sensitivity, retinal nerve fibre analysis and monocular and binocular visual field measures (monocular 24-2 and binocular integrated visual fields (IVF): IVF-60 and IVF-120). The analyses focused on the associations between the outcomes measures and severity and location of visual field loss, as this is the primary visual function affected by glaucoma. In Study 1a, we examined the association between visual field loss and health-related quality of life, measured by the Short Form 36-item Health Survey (SF-36). Greater binocular visual field loss, on both IVF measures, was associated with lower SF-36 physical component scores, adjusted for age and gender (Pearson's r =|0.32| to |0.36|, p<0.001). Furthermore, inferior visual field loss was more strongly associated with the SF-36 physical component than superior field loss. No association was found between visual field loss and SF-36 mental component scores. The association between visual field loss and functional status was examined in Study 1b. Functional status outcomes measures included a physical activity questionnaire (Physical Activity Scale for the Elderly, PASE), performance tests (six-minute walk test, timed up and go test and lower leg strength) and an overall functional status score. Significant, but weak, correlations were found between binocular visual field loss and PASE and overall functional status scores, adjusted for age and gender (Pearson's r =|0.24| to |0.33|, p<0.05). Greater inferior visual field loss, independent of superior visual field loss, was significantly associated with poorer physical performance results and lower overall functional status scores. In Study 1c, we examined the association between visual field loss and postural stability, using a swaymeter device which recorded body movement during four conditions: eyes open and closed, on a firm and foam surface. Greater binocular visual field loss was associated with increased postural sway, both on firm and foam surfaces, independent of age and gender (Pearson’s r =|0.44| to |0.46|, p <0.001). Furthermore, inferior visual field was a stronger contributor to postural stability, more so than the superior visual field, particularly on the foam condition with the eyes open. Greater visual field loss was associated with a reduction in the visual contribution to postural sway, which underlies the observed association with postural sway. The second component of the thesis examined the association between severity and location of visual field loss and falls during a 12-month longitudinal follow-up. The number of falls was assessed prospectively using monthly fall calendars. Of the 71 participants who successfully completed the follow up (mean age 73.9 ± 5.7 years), 44% reported one or more falls, and around 20% reported two or more falls. After adjusting for age and gender, every 10 points missed on the IVF-120 increased the rate of falls by 25% (rate ratio 1.25, 95% confidence interval 1.08 - 1.44) or every 5dB reduction in IVF-60 increased the rate of falls by 47% (rate ratio 1.47, 95% confidence interval 1.16 - 1.87). Inferior visual field loss was a significant predictor of falls, more so than superior field loss, highlighting the importance of the inferior visual field area in safe and efficient navigation. Further analyses indicated that postural stability, more so than functional status, may be a potential mediating factor in the relationship between visual field loss and falls. Future research is required to confirm this causal pathway. In addition, the use of topical beta-blocker medications was not associated with an increased rate of falls in this cohort, compared with the use of other topical anti-glaucoma medications. In summary, greater binocular visual field loss among older adults with glaucoma was associated with poorer health-related quality of life in the physical domain, reduced functional status, greater postural instability and higher rates of falling. When the location of visual field loss was examined, inferior visual field loss was consistently more strongly associated with these outcomes than superior visual field loss. Insights gained from this research improve our understanding of the association between glaucomatous visual field loss and disability, and its link with falls among older adults. The clinical implications of this research include the need to include visual field screening in falls risk assessments among older adults and to raise awareness of these findings to eye care practitioners and adults with glaucoma. The findings also assist in developing further research to examine strategies to reduce disability and prevent falls among older adults with glaucoma to promote healthy ageing and independence for these individuals.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The release of the Australian Curriculum English (ACE) by the Australian Curriculum, Assessment and Reporting Authority (ACARA) has revived debates about the role of grammar as English content knowledge. We consider some of the discussion circulating in the mainstream media vis-à-vis the intent of the ACE. We conclude that this curriculum draws upon the complementary tenets of traditional Latin-based grammar and systemic functional linguistics across the three strands of Language, Literature and Literacy in innovative ways. We argue that such an approach is necessary for working with contemporary multimodal and cross-cultural texts. To demonstrate the utility of this new approach, we draw out a set of learning outcomes from Year 6 and then map out a framework for relating the outcomes to the form and function of multimodal language. As a case in point, our analysis is of two online Coca-Cola advertising texts, one each from South Korea and Australia.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Background and significance: Older adults with chronic diseases are at increasing risk of hospital admission and readmission. Approximately 75% of adults have at least one chronic condition, and the odds of developing a chronic condition increases with age. Chronic diseases consume about 70% of the total Australian health expenditure, and about 59% of hospital events for chronic conditions are potentially preventable. These figures have brought to light the importance of the management of chronic disease among the growing older population. Many studies have endeavoured to develop effective chronic disease management programs by applying social cognitive theory. However, limited studies have focused on chronic disease self-management in older adults at high risk of hospital readmission. Moreover, although the majority of studies have covered wide and valuable outcome measures, there is scant evidence on examining the fundamental health outcomes such as nutritional status, functional status and health-related quality of life. Aim: The aim of this research was to test social cognitive theory in relation to self-efficacy in managing chronic disease and three health outcomes, namely nutritional status, functional status, and health-related quality of life, in older adults at high risk of hospital readmission. Methods: A cross-sectional study design was employed for this research. Three studies were undertaken. Study One examined the nutritional status and validation of a nutritional screening tool; Study Two explored the relationships between participants. characteristics, self-efficacy beliefs, and health outcomes based on the study.s hypothesized model; Study Three tested a theoretical model based on social cognitive theory, which examines potential mechanisms of the mediation effects of social support and self-efficacy beliefs. One hundred and fifty-seven patients aged 65 years and older with a medical admission and at least one risk factor for readmission were recruited. Data were collected from medical records on demographics, medical history, and from self-report questionnaires. The nutrition data were collected by two registered nurses. For Study One, a contingency table and the kappa statistic was used to determine the validity of the Malnutrition Screening Tool. In Study Two, standard multiple regression, hierarchical multiple regression and logistic regression were undertaken to determine the significant influential predictors for the three health outcome measures. For Study Three, a structural equation modelling approach was taken to test the hypothesized self-efficacy model. Results: The findings of Study One suggested that a high prevalence of malnutrition continues to be a concern in older adults as the prevalence of malnutrition was 20.6% according to the Subjective Global Assessment. Additionally, the findings confirmed that the Malnutrition Screening Tool is a valid nutritional screening tool for hospitalized older adults at risk of readmission when compared to the Subjective Global Assessment with high sensitivity (94%), and specificity (89%) and substantial agreement between these two methods (k = .74, p < .001; 95% CI .62-.86). Analysis data for Study Two found that depressive symptoms and perceived social support were the two strongest influential factors for self-efficacy in managing chronic disease in a hierarchical multiple regression. Results of multivariable regression models suggested advancing age, depressive symptoms and less tangible support were three important predictors for malnutrition. In terms of functional status, a standard regression model found that social support was the strongest predictor for the Instrumental Activities of Daily Living, followed by self-efficacy in managing chronic disease. The results of standard multiple regression revealed that the number of hospital readmission risk factors adversely affected the physical component score, while depressive symptoms and self-efficacy beliefs were two significant predictors for the mental component score. In Study Three, the results of the structural equation modelling found that self-efficacy partially mediated the effect of health characteristics and depression on health-related quality of life. The health characteristics had strong direct effects on functional status and body mass index. The results also indicated that social support partially mediated the relationship between health characteristics and functional status. With regard to the joint effects of social support and self-efficacy, social support fully mediated the effect of health characteristics on self-efficacy, and self-efficacy partially mediated the effect of social support on functional status and health-related quality of life. The results also demonstrated that the models fitted the data well with relative high variance explained by the models, implying the hypothesized constructs under discussion were highly relevant, and hence the application for social cognitive theory in this context was supported. Conclusion: This thesis highlights the applicability of social cognitive theory on chronic disease self-management in older adults at risk of hospital readmission. Further studies are recommended to validate and continue to extend the development of social cognitive theory on chronic disease self-management in older adults to improve their nutritional and functional status, and health-related quality of life.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Value Management (VM) is a proven methodology that provides a structured framework using supporting tools and techniques that facilitate effective decision-making in many types of projects, thus achieving ‘best value’ for clients. It offers an exceptionally robust approach to exploring the need and function of projects to be aligned with client’s objectives. The functional analysis and creativity phases of VM are crucial as it focused on utilising innovative thinking to understand the objectives of clients’ projects and provide value-adding solutions at the early discovery stages of projects. There is however a perception of VM as just being another cost-cutting tool, which has overshadowed the fundamental benefits of the method, therefore negating both influence and wider use in the construction industry. This paper describes findings from a series of case studies conducted at project and corporate levels of a current public funded infrastructure projects in Malaysia. The study aims to investigate VM processes practised by the project client organisation and evaluate the effects of project team involvement in VM workshops during the design-stage of these projects. The focus of the study is on how issues related to ‘upstream’ infrastructure design aimed at improving ‘downstream’ construction process on-site, are being resolved through multi-disciplinary team consideration and decision-making. Findings from the case studies indicate that the mix of disciplines of project team members at a design-stage of a VM workshop has minimal influence on improving construction processes. However, the degree of interaction, institutionalized thinking, cultural dimensions and visualization aids adopted, have a significant impact in maximizing creativity amongst project team members during VM workshop. The case studies conducted for this research have focused on infrastructure projects that utilise traditional VM workshop as client’s chosen VM methodology to review and develop designs. Documents review and semi-structured interview with project teams are used as data collection techniques for the case study. The significant outcomes of this research are expected to offer alternative perspectives for construction professionals and clients to minimise the constraints and strengthen strategies for implementing VM on future projects.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Objective. To investigate the reliability and validity of five squat-based loading tests that are clinically appropriate for jumper's knee. The loading tests were step up, double leg squat, double leg squat on a 25-degree decline (decline squat), single leg decline squat, and decline hop. Design. Cross-sectional controlled cohort. Subjects without knee pain comprised controls, those with extensor tendon pain comprised the jumper's knee group. Setting. Institutional athlete study group in Australia Participants. Fifty-six elite adolescent basketball players participated in this study, thirteen comprised the jumper's knee group, fifteen athletes formed a control group. Intervention. Each subject performed each loading test for baseline and reliability data on the first testing day. Subjects then performed three days of intensive (6 h daily) basketball training, after which each loading test was reexamined. Main outcome measures. Eleven point interval scale for pain. Results. The tests that best detected a change in pain due to intensive workload were the single leg decline squat and single leg decline hop. This study found that decline tests have better discriminative ability than the standard squat to detect change in jumper's knee pain due to intensive training. The typical error for these tests ranged from 0.3 to 0.5, however, caution should be exercised in the interpretation of these reliability figures due to relatively low scores. Conclusions. The single leg decline squat is recommended in the physical assessment of adolescent jumper's knee. The decline squat was selected as the best clinical test over the decline hop because it was easier to standardise performance.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Background No study relating the changes obtained in the architecture of erector spinae (ES) muscle were registered with ultrasound and different intensities of muscle contraction recorded by surface EMG (electromyography) on the ES muscle was found. The aim of this study was analyse the relationship in the response of the ES muscle during isometric moderate and light lumbar isometric extension considering architecture and functional muscle variables. Methods Cross-sectional study. 46 subjects (52% men) with a group mean age of 30.4 (±7.78). The participants developed isometric lumbar extension while performing moderate and low isometric trunk and hip extension in a sitting position with hips flexed 90 degrees and the lumbar spine in neutral position. During these measurements, electromyography recordings and ultrasound images were taken bilaterally. Bilaterally pennation angle, muscle thickness, torque and muscle activation were measured. This study was developed at the human movement analysis laboratory of the Health Science Faculty of the University of Malaga (Spain). Results Strong and moderate correlations were found at moderate and low intensities contraction between the variable of the same intensity, with correlation values ranging from 0.726 (Torque Moderate – EMG Left Moderate) to 0.923 (Angle Left Light – Angle Right Light) (p < 0.001). This correlation is observed between the variables that describe the same intensity of contraction, showing a poor correlation between variables of different intensities. Conclusion There is a strong relationship between architecture and function variables of ES muscle when describe an isometric lumbar extension at light or moderate intensity. Keywords: Ultrasonography; Surface electromyography; Thickness; Pennation angle; Erector spinae

Relevância:

30.00% 30.00%

Publicador:

Resumo:

BACKGROUND Chemotherapy-induced nausea and vomiting (CINV) remain prevalent among cancer patients despite pharmacological advances in CINV therapy. Patients can initiate nonpharmacologic strategies, which potentially play an important role as adjuncts to pharmacological agents in alleviating CINV. Some studies have explored nausea and vomiting self-management (NVSM) behaviors among patients in Western settings; however, little is known about the NVSM behaviors of patients in China. OBJECTIVES This study examines NVSM behaviors of Chinese cancer patients. METHODS A cross-sectional survey was conducted in a specialist cancer hospital in southeast China. RESULTS A sample of 255 cancer patients was recruited. A mean of 8.56 (±3.15) NVSM behaviors was reported. Most NVSM behaviors were rated as moderately effective and were implemented with moderate self-efficacy. Higher distress levels, better functional status, previous similar symptom experiences, receiving chemotherapy as an inpatient, and greater support from multiple levels were related to greater engagement in NVSM; higher self-efficacy levels pertaining to NVSM behaviors were associated with reports of more relief from specific NVSM behaviors. CONCLUSIONS A range of NVSM strategies was initiated by Chinese cancer patients and provided some relief. A range of individual, health status, and environmental factors influenced engagement with and relief from NVSM behaviors. IMPLICATIONS FOR PRACTICE To enhance Chinese patients' NVSM, patients should be supported to engage in behaviors including taking antiemetics, modifying their diet, using psychological strategies, and creating a pleasant environment. The findings highlight the importance of enhancing patients' self-efficacy in NVSM, alleviating symptom distress, and improving social support to achieve better outcomes.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

BACKGROUND Research on engineering design is a core area of concern within engineering education and a fundamental understanding of how engineering students approach and undertake design is necessary in order to develop effective design models and pedagogies. Understanding the factors related to design experiences in education and how they affect student practice can help educators as well as designers to leverage these factors as part of the design process. PURPOSE This study investigated the design practices of first-year engineering students’ and their experiences with a first-year engineering course design project. The research questions that guided the investigation were: 1. From a student perspective, what design parameters or criteria are most important? 2. How does this perspective impact subsequent student design practice throughout the design process? DESIGN/METHOD The authors employed qualitative multi-case study methods (Miles & Huberman, 1994) in order to the answer the research questions. Participant teams were observed and video recorded during team design meetings in which they researched the background for the design problem, brainstormed and sketched possible solutions, as well as built prototypes and final models of their design solutions as part of a course design project. Analysis focused on explanation building (Yin, 2009) and utilized within-case and cross-case analysis (Miles & Huberman, 1994). RESULTS We found that students focused disproportionally on the functional parameter, i.e. the physical implementation of their solution, and the possible/applicable parameter, i.e. a possible and applicable solution that benefited the user, in comparison to other given parameters such as safety and innovativeness. In addition, we found that individual teams focused on the functional and possible/ applicable parameters in early design phases such as brainstorming/ ideation and sketching. When prompted to discuss these non-salient parameters (from the student perspective) in the final design report, student design teams often used a post-hoc justification to support how the final designs fit the parameters that they did not initially consider. CONCLUSIONS This study suggests is that student design teams become fixated on (and consequently prioritize) certain parameters they interpret as important because they feel these parameters were described more explicitly in terms how they were met and assessed. Students fail to consider other parameters, perceived to be less directly assessable, unless prompted to do so. Failure to consider other parameters in the early design phases subsequently affects their approach in design phases as well. Case studies examining students’ study strategies within three Australian Universities illustrate similarities with some student approaches to design.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Background A feature of epithelial to mesenchymal transition (EMT) relevant to tumour dissemination is the reorganization of actin cytoskeleton/focal contacts, influencing cellular ECM adherence and motility. This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/δEF1. These genes, overexpressed in breast carcinomas, are known targets of growth factor-initiated pathways, however it is less clear how alterations in ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST) induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC. Methods PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/δEF1) and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR) and immunofluorescence +/- cycloheximide. Actin and focal contacts (paxillin) were visualized by confocal microscopy. A public database of human breast cancers was assessed for expression of Snail1 and Snail2 in relation to outcome. Results When PMC42-LA were treated with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/δEF1 induction seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and independently of gene transcription. Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4) and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4). Examination of the public database of breast cancers revealed tumours exhibiting higher Snail1 expression have an increased risk of disease-recurrence. This was not seen for Snail2, and Zeb1/δEF1 showed a reverse correlation with lower expression values being predictive of increased risk. Conclusion ST in combination with EGF directed a greater EMT via actin depolymerisation and focal contact size reduction, resulting in a loosening of cell-ECM attachment along with Snail1-Zeb1/δEF1 induction. This appeared fundamentally different to the EGF-induced EMT, highlighting the multiple pathways which can regulate EMT. Our findings add support for a functional role for Snail1 in invasive breast cancer.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Background Hallux valgus (HV) is highly prevalent and associated with progressive first metatarsophalangeal joint subluxation and osteoarthritis. The link between structural HV deformity and foot pain is unclear. This study investigated possible explanatory factors surrounding foot pain in HV, including radiographic HV angle and signs of joint degeneration. Methods Participants were 60 adults (53 female) with HV aged 20 to 75 years. Participant demographics and a range of radiographic, clinical and functional measures were considered potential correlates of foot pain. Self-reported foot pain (visual analogue scales and a dichotomous definition) was considered the dependent variable. Multivariate modelling was used to determine which characteristics and measures explained pain, with univariate analyses first used to screen potential variables. Results Approximately 20 to 30% of the variance in foot pain associated with HV could be explained by patient characteristics such as poorer general health status, lower educational attainment and increased occupational physical activity levels, in combination with some dynamic physical characteristics such as hallux plantarflexion weakness and reduced force-time integral under the second metatarsal during gait. Neither increasing lateral deviation of the hallux (HV angle) nor presence of first metatarsophalangeal joint osteoarthritis was associated with foot pain. Conclusions This study shows that passive structural factors, including HV angle, do not appear to be significant correlates of foot pain intensity in HV. Our data demonstrate the importance of considering patient characteristics such as general health and physical activity levels when assessing foot pain associated with HV.