Sex-specific compromised bone healing in female rats might be associated with a decrease in mesenchymal stem cell quantity

Introduction The clinically known importance of patient sex as a major risk factor for compromised bone healing is poorly reflected in animal models. Consequently, the underlying cellular mechanisms remain elusive. Because mesenchymal stem cells (MSCs) are postulated to regulate tissue regeneration and give rise to essential differentiated cell types, they may contribute to sex-specific differences in bone healing outcomes. Methods We investigated sex-specific variations in bone healing and associated differences in MSC populations. A 1.5 mm osteotomy gap in the femora of 8 male and 8 female 12-month-old Sprague-Dawley rats was stabilized by an external fixator. Healing was analyzed in terms of biomechanical testing, bridging and callus size over time (radiography at 2, 4, and 6 weeks after surgery), and callus volume and geometry by μCT at final follow-up. MSCs were obtained from bone marrow samples of an age-matched group of 12 animals (6 per gender) and analyzed for numbers of colony-forming units (CFUs) and their capacity to differentiate and proliferate. The proportion of senescent cells was determined by β-galactosidase staining. Results Sex-specific differences were indicated by a compromised mechanical competence of the callus in females compared with males (maximum torque at failure, p = 0.028). Throughout the follow-up, the cross-sectional area of callus relative to bone was reduced in females (p ≤ 0.01), and the bridging of callus was delayed (p 2weeks = 0.041). μCT revealed a reduced callus size (p = 0.003), mineralization (p = 0.003) and polar moment of inertia (p = 0.003) in female animals. The female bone marrow contained significantly fewer MSCs, represented by low CFU numbers in both femora and tibiae (p femur = 0.017, p tibia = 0.010). Functional characteristics of male and female MSCs were similar. Conclusion Biomechanically compromised and radiographically delayed bone formation were distinctive in female rats. These differences were concomitant with a reduced number of MSCs, which may be causative for the suboptimal bone healing.

The impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy on survival in patients with a history of breast cancer – a population-based data linkage study

Prophylactic surgery including hysterectomy and bilateral salpingo-oophorectomy (BSO) is recommended in BRCA positive women, while in women from the general population, hysterectomy plus BSO may increase the risk of overall mortality. The effect of hysterectomy plus BSO on women previously diagnosed with breast cancer is unknown. We used data from a population-base data linkage study of all women diagnosed with primary breast cancer in Queensland, Australia between 1997 and 2008 (n=21,067). We fitted flexible parametric breast cancer specific and overall survival models with 95% confidence intervals (also known as Royston-Parmar models) to assess the impact of risk-reducing surgery (removal of uterus, one or both ovaries). We also stratified analyses by age 20-49 and 50-79 years, respectively. Overall, 1,426 women (7%) underwent risk-reducing surgery (13% of premenopausal women and 3% of postmenopausal women). No women who had risk-reducing surgery, compared to 171 who did not have risk-reducing surgery developed a gynaecological cancer. Overall, 3,165 (15%) women died, including 2,195 (10%) from breast cancer. Hysterectomy plus BSO was associated with significantly reduced risk of death overall (adjusted HR = 0.69, 95% CI 0.53-0.89; P =0.005). Risk reduction was greater among premenopausal women, whose risk of death halved (HR, 0.45; 95% CI, 0.25-0.79; P < 0.006). This was largely driven by reduction in breast cancer-specific mortality (HR, 0.43; 95% CI, 0.24-0.79; P < 0.006). This population-based study found that risk-reducing surgery halved the mortality risk for premenopausal breast cancer patients. Replication of our results in independent cohorts, and subsequently randomised trials are needed to confirm these findings.

Inelastic finite element analysis of composite beams on the basis of the plastic hinge approach

This paper emphasizes material nonlinear effects on composite beams with recourse to the plastic hinge method. Numerous combinations of steel and concrete sections form arbitrary composite sections. Secondly, the material properties of composite beams vary remarkably across its section from ductile steel to brittle concrete. Thirdly, concrete is weak in tension, so composite section changes are dependent on load distribution. To this end, the plastic zone approach is convenient for inelastic analysis of composite sections that can evaluate member resistance, including material nonlinearities, by routine numerical integration with respect to every fiber across the composite section. As a result, many researchers usually adopt the plastic zone approach for numerical inelastic analyses of composite structures. On the other hand, the plastic hinge method describes nonlinear material behaviour of an overall composite section integrally. Consequently, proper section properties for use in plastic hinge spring stiffness are required to represent the material behaviour across the arbitrary whole composite section. In view of numerical efficiency and convergence, the plastic hinge method is superior to the plastic zone method. Therefore, based on the plastic hinge approach, how to incorporate the material nonlinearities of the arbitrary composite section into the plastic hinge stiffness formulation becomes a prime objective of the present paper. The partial shear connection in this paper is by virtue of the effective flexural rigidity as AISC 1993 [American Institute of Steel Construction (AISC). Load and resistance factor design specifications. 2nd ed., Chicago; 1993]. Nonlinear behaviour of different kinds of composite beam is investigated in this paper, including two simply supported composite beams, a cantilever and a two span continuous composite beam.

Applying the ecological model of behavior change to a physical activity trial in retirement communities : description of the study protocol

Objectives To describe the intervention protocol for the first multilevel ecological intervention for physical activity in retirement communities that addresses individual, interpersonal and community influences on behavior change. Design A cluster randomized controlled trial design was employed with two study arms: a physical activity intervention and an attention control successful aging condition. Setting Sixteen continuing care retirement communities in San Diego County. Participants Three hundred twenty older adults, aged 65 years and older, are being recruited to participate in the trial. In addition, peer leaders are being recruited to lead some study activities, especially to sustain the intervention after study activities ceased. Intervention Participants in the physical activity trial receive individual, interpersonal and community intervention components. The individual level components include pedometers, goal setting and individual phone counseling. The interpersonal level components include group education sessions and peer-led activities. The community level components include resource audits and enumeration, tailored walking maps, and community improvement projects. The successful aging group receives individual and group attention about successful aging topics. Measurements The main outcome is light to moderate physical activity, measured objectively by accelerometry. Other objective outcomes included physical functioning, blood pressure, physical fitness, and cognitive functioning. Self report measures include depressive symptoms and health related quality of life. Results The intervention is being delivered successfully in the communities and compliance rates are high. Conclusion Ecological Models call for interventions that address multiple levels of the model. Previous studies have not included components at each level and retirement communities provide a model environment to demonstrate how to implement such an intervention.

The impact of neighborhood walkability on walking : does it differ across adult life stage and does neighborhood buffer size matter?

We explored the impact of neighborhood walkability on young adults, early-middle adults, middle-aged adults, and older adults' walking across different neighborhood buffers. Participants completed the Western Australian Health and Wellbeing Surveillance System Survey (2003–2009) and were allocated a neighborhood walkability score at 200 m, 400 m, 800 m, and 1600 m around their home. We found little difference in strength of associations across neighborhood size buffers for all life stages. We conclude that neighborhood walkability supports more walking regardless of adult life stage and is relevant for small (e.g., 200 m) and larger (e.g., 1600 m) neighborhood buffers.

Cytotoxicity of topical antimicrobial agents used in burn wounds in Australasia

BACKGROUND: Burn sepsis is a leading cause of mortality and morbidity in patients with major burns. The use of topical antimicrobial agents has helped improve the survival of these patients. Silvazine (Sigma Pharmaceuticals, Melbourne, Australia) (1% silver sulphadiazine and 0.2% chlorhexidine digluconate) is used exclusively in Australasia, and there is no published study on its cytotoxicity. This study compared the relative cytotoxicity of Silvazine with 1% silver sulphadiazine (Flamazine (Smith & Nephew Healthcare, Hull, UK)) and a silver-based dressing (Acticoat (Smith & Nephew Healthcare, Hull, UK)). METHODS: Dressings were applied to the centre of culture plates that were then seeded with keratinocytes at an estimated 25% confluence. The plates were incubated for 72 h and culture medium and dressings then removed. Toluidine blue was added to stain the remaining keratinocytes. Following removal of the dye, the plates were photographed under standard conditions and these digital images were analysed using image analysis software. Data was analysed using Student's t-test. RESULTS: In the present study, Silvazine is the most cytotoxic agent. Seventy-two hour exposure to Silvazine in the present study results in almost no keratinocyte survival at all and a highly statistically significant reduction in cell survival relative to control, Acticoat and Flamazine (P<0.001, P<0.01, P<0.01, respectively). Flamazine is associated with a statistically significant reduction in cell numbers relative to control (P<0.05), but is much less cytotoxic than Silvazine (P<0.005). CONCLUSION: In this in-vitro study comparing Acticoat, Silvazine and Flamazine, Silvazine shows an increased cytotoxic effect, relative to control, Flamazine and Acticoat. An in-vivo study is required to determine whether this effect is carried into the clinical setting.

Interleukin-1β stimulates human renal fibroblast proliferation and matrix protein production by means of a transforming growth factor-β-dependent mechanism

One of the hallmarks of progressive renal disease is the development of tubulointerstitial fibrosis. This is frequently preceded by macrophage infiltration, raising the possibility that macrophages relay fibrogenic signals to resident tubulointerstitial cells. The aim of this study was to investigate the potentially fibrogenic role of interleukin-1beta (IL-1beta), a macrophage-derived inflammatory cytokine, on cortical fibroblasts (CFs). Primary cultures of human renal CFs were established and incubated for 24 hours in the presence or absence of IL-1beta. We found that IL-1beta significantly stimulated DNA synthesis (356.7% +/- 39% of control, P <.003), fibronectin secretion (261.8 +/- 11% of control, P <.005), collagen type 1 production, (release of procollagen type 1 C-terminal-peptide, 152.4% +/- 26% of control, P <.005), transforming growth factor-beta (TGF-beta) secretion (211% +/- 37% of control, P <.01), and nitric oxide (NO) production (342.8% +/- 69% of control, P <.002). TGF-beta (1 ng/mL) and the phorbol ester phorbol 12-myristate 13-acetate (PMA, 25 nmol/L) produced fibrogenic effects similar to those of IL-1beta. Neither a NO synthase inhibitor (N(G)-methyl-l-arginine, 1 mmol/L) nor a protein kinase C (PKC) inhibitor (bis-indolylmaleimide 1, 1 micromol/L) altered the enhanced level of fibronectin secretion or DNA synthesis seen in response to IL-1beta treatment. However, addition of a TGF-beta-neutralizing antibody significantly reduced IL-1beta-induced fibronectin secretion (IL-1beta + IgG, 262% +/- 72% vs IL-1beta + alphaTGF-beta 156% +/- 14%, P <.02), collagen type 1 production (IL-1beta + IgG, 176% +/- 28% vs IL-1beta + alphaTGF-beta, 120% +/- 14%, P <.005) and abrogated IL-1beta-induced DNA synthesis (245% +/- 49% vs 105% +/- 21%, P <.005). IL-1beta significantly stimulated CF DNA synthesis and production of fibronectin, collagen type 1, TGFbeta, and NO. The fibrogenic and proliferative action of IL-1beta on CF appears not to involve activation of PKC or production of NO but is at least partly TGFbeta-dependent.

The evaluation of a clinical scar scale for porcine burn scars

This study describes the evaluation of a clinical scar scale for our porcine burn scars, which includes scar cosmetic outcome, colour, height and hair, supplemented with reference porcine scar photographs representing each scar outcome and scar colour scores. A total of 72 porcine burn scars at week 6 after burn were rated in vivo and/or on photographs. Good agreements were achieved for both intra-rater reliability (correlation is 0.86-0.98) and inter-rater reliability (ICC=80-85%). The results showed statistically significant correlations for each pair in this clinical scar scale (p<0.01), with the best correlation found between scar cosmetic outcome and scar colour. A multivariate principle components analysis revealed that this clinical scar assessment was highly correlated with scar histology, wound size, and re-epithelialisation data (p<0.001). More severe scars are clinically characterised by darker purple colouration, more elevation, no presence of hair, histologically by thicker scar tissue, thinner remaining normal dermis, are more likely to have worse contraction, and slower re-epithelialisation. This study demonstrates that our clinical scar scale is a reliable, independent and valuable tool for assessing porcine burn outcome and truthfully reflects scar appearance and function. To our knowledge, this is the first study demonstrating a high correlation between clinical scar assessment and scar histology, wound contraction and re-epithelialisation data on porcine burn scars. We believe that the successful use of porcine scar scales is invaluable for assessing potential human burn treatments.

Factors associated with the isolation of Nontuberculous mycobacteria (NTM) from a large municipal water system in Brisbane, Australia

Background Nontuberculous mycobacteria (NTM) are normal inhabitants of a variety of environmental reservoirs including natural and municipal water. The aim of this study was to document the variety of species of NTM in potable water in Brisbane, QLD, with a specific interest in the main pathogens responsible for disease in this region and to explore factors associated with the isolation of NTM. One-litre water samples were collected from 189 routine collection sites in summer and 195 sites in winter. Samples were split, with half decontaminated with CPC 0.005%, then concentrated by filtration and cultured on 7H11 plates in MGIT tubes (winter only). Results Mycobacteria were grown from 40.21% sites in Summer (76/189) and 82.05% sites in winter (160/195). The winter samples yielded the greatest number and variety of mycobacteria as there was a high degree of subculture overgrowth and contamination in summer. Of those samples that did yield mycobacteria in summer, the variety of species differed from those isolated in winter. The inclusion of liquid media increased the yield for some species of NTM. Species that have been documented to cause disease in humans residing in Brisbane that were also found in water include M. gordonae, M. kansasii, M. abscessus, M. chelonae, M. fortuitum complex, M. intracellulare, M. avium complex, M. flavescens, M. interjectum, M. lentiflavum, M. mucogenicum, M. simiae, M. szulgai, M. terrae. M. kansasii was frequently isolated, but M. avium and M. intracellulare (the main pathogens responsible for disease is QLD) were isolated infrequently. Distance of sampling site from treatment plant in summer was associated with isolation of NTM. Pathogenic NTM (defined as those known to cause disease in QLD) were more likely to be identified from sites with narrower diameter pipes, predominantly distribution sample points, and from sites with asbestos cement or modified PVC pipes. Conclusions NTM responsible for human disease can be found in large urban water distribution systems in Australia. Based on our findings, additional point chlorination, maintenance of more constant pressure gradients in the system, and the utilisation of particular pipe materials should be considered.

Incidental treatment effects of CBT on suicidal ideation and hopelessness

Background: Depression and alcohol misuse are among the most prevalent diagnoses in suicide fatalities. The risk posed by these disorders is exacerbated when they co-occur. Limited research has evaluated the effectiveness of common depression and alcohol treatments for the reduction of suicide vulnerability in individuals experiencing comorbidity. Methods: Participants with depressive symptoms and hazardous alcohol use were selected from two randomised controlled trials. They had received either a brief (1 session) intervention, or depression-focused cognitive behaviour therapy (CBT), alcohol-focused CBT, therapist-delivered integrated CBT, computer-delivered integrated CBT or person-centred therapy (PCT) over a 10-week period. Suicidal ideation, hopelessness, depression severity and alcohol consumption were assessed at baseline and 12-month follow-up. Results: Three hundred three participants were assessed at baseline and 12 months. Both suicidal ideation and hopelessness were associated with higher severity of depressive symptoms, but not with alcohol consumption. Suicidal ideation did not improve significantly at follow-up, with no differences between treatment conditions. Improvements in hopelessness differed between treatment conditions; hopelessness improved more in the CBT conditions compared to PCT and in single-focused CBT compared to integrated CBT. Limitations: Low retention rates may have impacted on the reliability of our findings. Combining data from two studies may have resulted in heterogeneity of samples between conditions. Conclusions: CBT appears to be associated with reductions in hopelessness in people with co-occurring depression and alcohol misuse, even when it is not the focus of treatment. Less consistent results were observed for suicidal ideation. Establishing specific procedures or therapeutic content for clinicians to monitor these outcomes may result in better management of individuals with higher vulnerability for suicide.

Empirical approaches in knowledge city research

In the 21st century, it has become apparent that ‘knowledge’ is a major factor of postmodern production (Yigitcanlar et al., 2007). Beyond this, in today’s rapidly globalizing world, knowledge, along with the social and technological settings, is seen as a key to secure economic prosperity and quality of life (Yigitcanlar et al., 2008a). However, limiting the benefits of a ‘knowledge-based development’ to only economic gains—and to a degree to social ones—is quite a narrow sighted view (Yigitcanlar et al., 2008b). Thus, the concept of ‘knowledge-based urban development’ is coined to bring economic prosperity, environmental sustainability, a just socio-spatial order and good governance to cities, and as a result producing a purposefully designed city—i.e., ‘knowledge city’—generating positive environmental and governance outcomes as well as economic and societal ones (Yigitcanlar, 2011; Carrillo et al., 2014).

Brief guided imagery and body scanning interventions reduce food cravings

Elaborated Intrusion (EI) Theory proposes that cravings occur when involuntary thoughts about food are elaborated; a key part of elaboration is affectively-charged imagery. Craving can be weakened by working memory tasks that block imagery. EI Theory predicts that cravings should also be reduced by preventing involuntary thoughts being elaborated in the first place. Research has found that imagery techniques such as body scanning and guided imagery can reduce the occurrence of food thoughts. This study tested the prediction that these techniques also reduce craving. We asked participants to abstain from food overnight, and then to carry out 10 min of body scanning, guided imagery, or a control mind wandering task. They rated their craving at 10 points during the task on a single item measure, and before and after the task using the Craving Experience Questionnaire. While craving rose during the task for the mind wandering group, neither the guided imagery nor body scanning group showed an increase. These effects were not detected by the CEQ, suggesting that they are only present during the competing task. As they require no devices or materials and are unobtrusive, brief guided imagery strategies might form useful components of weight loss programmes that attempt to address cravings.

High coexpression of both EGFR and IGF1R correlates with poor patient prognosis in resected non-small-cell lung cancer

Background Recent experimental and biomarker evidence indicates that the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1 (IGF1R) interact in the pathogenesis of malignant epithelial tumors, including lung cancer. This study examines the expression of both receptors and their prognostic significance in surgically resected non-small-cell lung cancer (NSCLC). Methods EGFR and IGF1R expression were evaluated in 184 patients with NSCLC (83 squamous cell carcinomas [SCCs], 83 adenocarcinomas [ADCs], and 18 other types) using immunohistochemical (IHC) analysis. Expression of both receptors was examined in matched fresh frozen normal and tumor tissues from 40 patients with NSCLC (20 SCCs and 20 ADCs) by Western blot analysis. Results High EGFR expression was detected in 51% of patients, and SCCs had higher EGFR expression than did non-SCCs (57.4% vs. 42.5%; P =.028). High IGF1R expression was observed in 53.8% of patients, with SCC having higher expression than non-SCC (62.6% vs. 37.3%; P =.0004). A significant association was shown between EGFR and IGF1R protein overexpression (P <.005). Patients with high expression of both receptors had a poorer overall survival (OS) (P =.04). Higher EGFR and IGF1R expression was detected in resected tumors relative to matched normal tissues (P =.0004 and P =.0009), with SCC having higher expression levels than ADC. Conclusion Our findings indicate a close interrelationship between EGFR and IGF1R. Coexpression of both receptors correlates with poor survival. This subset of patients may benefit from treatments cotargeting EGFR and IGF1R. © 2014 Elsevier Inc. All rights reserved.

Linking dynamic-capability portfolios and innovation outcomes

The objective of this paper is to explore the relationship between dynamic capabilities and different types of online innovations. Building on qualitative data from the publishing industry, our analysis revealed that companies that had relatively strong dynamic capabilities in all three areas (sensing, seizing and reconfiguration) seem to produce innovations that combine their existing capabilities on either the market or the technology dimension with new capabilities on the other dimension thus resulting in niche creation and revolutionary type innovations. Correspondingly, companies with a weaker or more one-sided set of dynamic capabilities seem to produce more radical innovations requiring both new market and technological capabilities. The study therefore provides an empirical contribution to the emerging work on dynamic capabilities through its in-depth investigation of the capabilities of the four case firms, and by mapping the patterns between the firm's portfolio of dynamic capabilities and innovation outcomes.

Exploring retinal markers of diabetic neuropathy

Purpose To investigate the application of retinal nerve fibre layer (RNFL) thickness as a marker for severity of diabetic peripheral neuropathy (DPN) in people with Type 2 diabetes. Methods This was a cross-sectional study whereby 61 participants (mean age 61 [41-75 years], mean duration of diabetes 14 [1-40 years], 70% male) with Type 2 diabetes and DPN underwent optical coherence tomography (OCT) scans. Global and 4 quadrant (TSNI) RNFL thicknesses were measured at 3.45mm around the optic nerve head of one eye. Neuropathy disability score (NDS) was used to assess the severity of DPN on a 0 to 10 scale. Participants were divided into three age-matched groups representing mild (NDS=3-5), moderate (NDS=6-8) and severe (NDS=9-10) neuropathy. Two regression models were fitted for statistical analysis: 1) NDS scores as co-variate for global and quadrant RNFL thicknesses, 2) NDS groups as a factor for global RNFL thickness only. Results Mean (SD) RNFL thickness (µm) was 103(9) for mild neuropathy (n=34), 101(10) for moderate neuropathy (n=16) and 95(13) in the group with severe neuropathy (n=11). Global RNFL thickness and NDS scores were statistically significantly related (b=-1.20, p=0.048). When neuropathy was assessed across groups, a trend of thinner mean RNFL thickness was observed with increasing severity of neuropathy; however, this result was not statistically significant (F=2.86, p=0.065). TSNI quadrant analysis showed that mean RNFL thickness reduction in the inferior quadrant was 2.55 µm per 1 unit increase in NDS score (p=0.005). However, the regression coefficients were not statistically significant for RNFL thickness in the superior (b=-1.0, p=0.271), temporal (b=-0.90, p=0.238) and nasal (b=-0.99, p=0.205) quadrants. Conclusions RNFL thickness was reduced with increasing severity of DPN and the effect was most evident in the inferior quadrant. Measuring RNFL thickness using OCT may prove to be a useful, non-invasive technique for identifying severity of DPN and may also provide additional insight into common mechanisms for peripheral neuropathy and RNFL damage.