Tumor-associated Endo180 requires stromal-derived LOX to promote metastatic prostate cancer cell migration on human ECM surfaces

The diverse composition and structure of extracellular matrix (ECM) interfaces encountered by tumor cells at secondary tissue sites can influence metastatic progression. Extensive in vitro and in vivo data has confirmed that metastasizing tumor cells can adopt different migratory modes in response to their microenvironment. Here we present a model that uses human stromal cell-derived matrices to demonstrate that plasticity in tumor cell movement is controlled by the tumor-associated collagen receptor Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) and the crosslinking of collagen fibers by stromal-derived lysyl oxidase (LOX). Human osteoblast-derived and fibroblast-derived ECM supported a rounded ‘amoeboid-like’ mode of cell migration and enhanced Endo180 expression in three prostate cancer cell lines (PC3, VCaP, DU145). Genetic silencing of Endo180 reverted PC3 cells from their rounded mode of migration towards a bipolar ‘mesenchymal-like’ mode of migration and blocked their translocation on human fibroblast-derived and osteoblast-derived matrices. The concomitant decrease in PC3 cell migration and increase in Endo180 expression induced by stromal LOX inhibition indicates that the Endo180-dependent rounded mode of prostate cancer cell migration requires ECM crosslinking. In conclusion, this study introduces a realistic in vitro model for the study of metastatic prostate cancer cell plasticity and pinpoints the cooperation between tumor-associated Endo180 and the stiff microenvironment imposed by stromal-derived LOX as a potential target for limiting metastatic progression in prostate cancer.     

The influence of simulations on family engagement – prospective early childhood educators’ perceptions

Nurturing experiences in preparation for prospective early childhood educators’ work with families during their training are critical for establishing empowering relationships. This article details a qualitative case study of 77 prospective early childhood educators engaged with the Parent, Family and Community Engagement Simulation. An electronic questionnaire exploring their beliefs regarding the use of the simulation was conducted at the Universidad Rey Juan Carlos (Spain). The results demonstrate the simulation can be a very effective classroom technique to provide students with the necessary competencies to engage with families effectively and promote school readiness. These results also suggest that the simulation provided important insights into how successful partnership occurs and how to strengthen relationships, helping students to reflect on the importance of family involvement.     

Design and Testing of BACRA,a Web-Based Tool for Middle Managers at Health Care Facilities to Lead the Search for Solutions to Patient Safety Incidents

BackgroundLack of time, lack of familiarity with root cause analysis, or suspicion that the reporting may result in negative consequences hinder involvement in the analysis of safety incidents and the search for preventive actions that can improve patient safety.ObjectiveThe aim was develop a tool that enables hospitals and primary care professionals to immediately analyze the causes of incidents and to propose and implement measures intended to prevent their recurrence.MethodsThe design of the Web-based tool (BACRA) considered research on the barriers for reporting, review of incident analysis tools, and the experience of eight managers from the field of patient safety. BACRA’s design was improved in successive versions (BACRA v1.1 and BACRA v1.2) based on feedback from 86 middle managers. BACRA v1.1 was used by 13 frontline professionals to analyze incidents of safety; 59 professionals used BACRA v1.2 and assessed the respective usefulness and ease of use of both versions.ResultsBACRA contains seven tabs that guide the user through the process of analyzing a safety incident and proposing preventive actions for similar future incidents. BACRA does not identify the person completing each analysis since the password introduced to hide said analysis only is linked to the information concerning the incident and not to any personal data. The tool was used by 72 professionals from hospitals and primary care centers. BACRA v1.2 was assessed more favorably than BACRA v1.1, both in terms of its usefulness (z=2.2, P=.03) and its ease of use (z=3.0, P=.003).ConclusionsBACRA helps to analyze incidents of safety and to propose preventive actions. BACRA guarantees anonymity of the analysis and reduces the reluctance of professionals to carry out this task. BACRA is useful and easy to use.     

Bacterial leakage in root canals filled with AH Plus and dentine bonding agents

Objective. The aim of this study was to compare the efficacy of different dentine adhesives in delaying the coronal bacterial leakage of Enterococcus faecalis in filled root canals. Materials and methods. Ninety-five lower incisors of patients >65 years of age were instrumented using the ProTaper® system and were irrigated with 1 mL of 2.5% sodium hypochlorite (NaOCl) alternated with 1 mL 17% EDTA between each file change. Final irrigation was performed with 5 mL of 17% EDTA and then flushed with 5 mL of distilled water. The teeth were randomly divided into five experimental groups (n = 15/group) and one of the following dentine adhesives was applied: (1) AdheSE®; (2) Excite® DSC; (3) Clearfil^? Protect Bond; (4) One Coat 7.0; or (5) Control group without adhesive. After filling the root canals, the samples were mounted on a double chamber device to evaluate the bacterial filtration of E. faecalis during a period of 240 days. The results underwent non-parametric Kaplan-Meier survival analysis and comparisons among groups were done using the Log-Rank test. Results. At 240 days, E. faecalis was detected in samples of all groups in the lower chamber. The highest survival value was obtained by One Coat 7.0, giving statistically significant differences from the other groups, whereas Clearfil^? Protect Bond, AdheSE® and Excite® DSC showed similar behaviours, likewise similar to the Control group. Conclusions. One Coat 7.0 adhesive system provides the longest survival value to delay E. faecalis coronal leakage in filled root canals.     

Acute inflammation induced by the biopsy of mouse mammary tumors promotes the development of metastasis

Development of metastasis in peripheral tissues is a major problem in the fight to cure breast cancer. Although it is becoming evident that chronic inflammation can contribute to tumor progression and metastasis, the effect of acute inflammation in primary tumor is less known. Using mouse models for breast cancer here we show that biopsy of mammary tumors increases the frequency of lung metastases. This effect is associated with the recruitment of inflammatory cells to the lung and elevated levels of certain cytokines such as IL-6 in the lung airways. Antiinflammatory treatment prior to and after the biopsy reduces the development of metastases triggered by the biopsy. In addition, while lack of IL-6 does not affect primary tumor development, it protects from increasing number of metastases upon biopsy. Thus, our studies show that in addition to chronic inflammation, acute immune response caused by invasive procedures in the primary tumor may cause an increased risk on peripheral metastases, but the risk could be decreased by anti-inflammatory treatments.