Living ethics: a stance and its implications in health ethics.

Moral or ethical questions are vital because they affect our daily lives: what is the best choice we can make, the best action to take in a given situation, and ultimately, the best way to live our lives? Health ethics has contributed to moving ethics toward a more experience-based and user-oriented theoretical and methodological stance but remains in our practice an incomplete lever for human development and flourishing. This context led us to envision and develop the stance of a "living ethics", described in this inaugural collective and programmatic paper as an effort to consolidate creative collaboration between a wide array of stakeholders. We engaged in a participatory discussion and collective writing process known as instrumentalist concept analysis. This process included initial local consultations, an exploratory literature review, the constitution of a working group of 21 co-authors, and 8 workshops supporting a collaborative thinking and writing process. First, a living ethics designates a stance attentive to human experience and the role played by morality in human existence. Second, a living ethics represents an ongoing effort to interrogate and scrutinize our moral experiences to facilitate adaptation of people and contexts. It promotes the active and inclusive engagement of both individuals and communities in envisioning and enacting scenarios which correspond to their flourishing as authentic ethical agents. Living ethics encourages meaningful participation of stakeholders because moral questions touch deeply upon who we are and who we want to be. We explain various aspects of a living ethics stance, including its theoretical, methodological, and practical implications as well as some barriers to its enactment based on the reflections resulting from the collaborative thinking and writing process.

Spontaneous fibroblast-derived pericyte recruitment in a human tissue-engineered angiogenesis model in vitro.

Cooperation between endothelial cells and pericytes is essential to the stabilization and maturation of blood microvessels. We developed a unique in vitro tissue-engineered model to study angiogenesis. The human endothelialized reconstructed connective tissue model promotes the formation of a three-dimensional branching network of capillary-like tubes (CLT) with closed lumens. The purpose of this work was to investigate whether pericytes were spontaneously recruited around CLT in the model. We demonstrated that smooth muscle α-actin (SMA)-positive cells were found closely associated with PECAM-1-positive capillaries in the model. Twelve percent (±2.6) of SMA-positive cells were detected along with 15% (±1.64) von Willebrand factor-positive endothelial cells in the culture system after 31 days of in vitro maturation. Conversely, no SMA-positive cells were detected in reconstructed connective tissues made solely of fibroblasts. Knowing that PDGF is a major factor in the recruitment of pericytes, we showed that blockade of the PDGFB receptor using the inhibitor AG1296 induced an overall 5, 2.6, and 2.4-fold decrease in the SMA-positive cells, von Willebrand factor-positive cells, and number of capillaries, respectively. Using combinations of human GFP-positive fibroblasts and endothelial cells, we demonstrated that pericytes were recruited from the fibroblast population in the model. In conclusion, our tissue-engineered culture system promotes the spontaneous formation of a network of capillaries and the recruitment of pericytes derived from fibroblasts. Since pericytes are essential components of the blood microvasculature, this culture system is a powerful model to study angiogenesis and endothelial cell/pericyte interactions in vitro.

Isolation and Culture of Human Dermal Microvascular Endothelial Cells.

Primary endothelial cells are needed for angiogenesis studies, and more particularly in the field of tissue engineering, to engineer pre-vascularized tissues. Investigations often use human umbilical vein endothelial cells due to their extensive characterization, but also because they are easy to obtain and isolate. An alternative is the use of human dermal microvascular endothelial cells, more representative of adult skin angiogenesis and vascularization processes. This chapter presents a detailed methodology to isolate and culture microvascular endothelial cells from skin biopsies based on enzymatic digestion and mechanical extraction.

Implementing infection prevention and control capacity building strategies within the context of Ebola outbreak in a "Hard-to-Reach" area of Liberia.

INTRODUCTION: In August 2014, WHO declared that Ebola outbreak ravaging West Africa including Liberia had become a Public Health Emergency of International Concern (PHEIC). Infection prevention and control (IPC) among healthcare workers was pivotal in reducing healthcare worker infection and containing the recent EVD outbreak. Hard to reach areas (HTRA) presents peculiar challenges in public health emergencies. We present the result of IPC capacity building strategies deployed in Gbarpolu County: an HTRA of Liberia. METHODS: Between April to October 2015, we conducted IPC training and mentorship at the county, district and facility levels in a selected HTRA of Liberia using the keep Safe, Keep Serving manual and the WHO core components of infection control. Serial follow-up assessments and mentoring using the Liberian Minimum standard tool for safe care in Liberian health facilities (MST) were done. RESULTS: 180 (100%) facility based healthcare workers were trained: including 59 clinicians (32%) and 121 (67%) non-clinicians. 100% of the healthcare workers in four selected very HTRAs were trained and underwent facility based-mentorship. Compliance with IPC practice increased: the MST score increased from 75% to 90% and for the MST score for waste management and isolation increased 60% to 87%. CONCLUSION: Strengthening the capacity of healthcare workers for IPC was instrumental for containing the EVD epidemic but also critical for routine safe and quality services. A culture of IPC among healthcare workers in HTRA can be implemented through capacity building and training.

Of all the nerve! A subcutaneous forelimb mass on a cat.

A 16-year-old, male, neutered cat had a 2.5 X 1.5 cm mass on the medial aspect of the right carpus. Cytologic examination of a fine-needle aspirate of the mass indicated a markedly pleomorphic population of plasmacytoid to histiocytic-appearing cells. The cytologic diagnosis was malignant neoplasia of probable mesenchymal or round cell origin. The right forelimb was surgically removed and the scapular, axillary, and prescapular lymph nodes were excised. Malignant fibrous histiocytoma was tentatively diagnosed histologically; however, the tumor cells subsequently were found to be negative for histiocytic (MAC 387, antitrypsin), T-cell (CD3), and B-lymphocyte (immunoglobulin light chains, Ly 5/CD45R) markers, and positive for glial fibrillary acidic protein, vimentin, and S-100. Based on the immunohistochemical results, the diagnosis was modified to malignant peripheral nerve sheath tumor (PNST). Six months after surgery, the cat was reported to be well and had no evidence of metastasis. PNSTs are rare tumors in cats, and are considered as synonymous with schwannomas, neurofibrosarcomas, and hemangiopericytomas. In this cat, the plasmacytoid and pleomorphic appearance of the PNSTcells in cytologic and histologic specimens was unusual, and made it difficult to reach an accurate diagnosis without immunocytochemistry.

Extracellular matrix deposition by fibroblasts is necessary to promote capillary-like tube formation in vitro.

The contribution of the cellular and fibrillar microenvironment to angiogenesis still remains unclear. Our purpose was to evaluate the effect of the extracellular matrix deposited by fibroblasts on the capacity of human endothelial cells to form capillaries in vitro. We have drastically decreased the amount of extracellular matrix surrounding fibroblasts in our model of endothelialized-reconstructed connective tissue (ERCT) by culturing it without ascorbate. Under these conditions, the number of capillary-like tubes (CLT) formed by endothelial cells was reduced by up to 10-fold after 31 days of culture compared to controls. This decrease was due neither to a variation of MMP-2 and MMP-9 secretion, nor to a reduction in the number of fibroblasts and/or endothelial cells, or a diminution of fibroblast growth factor 2 (FGF2) synthesis. The secretion of vascular endothelial growth factor (VEGF) by fibroblasts accounted for 25-70% of the capillary-like tube formation when tissues were cultured in the presence or absence of ascorbate, as demonstrated by VEGF-blocking studies. The culture of endothelial cells on a similar extracellular matrix but in the absence of living fibroblasts did not promote the formation of CLT, even when tissues were fed with fibroblast-conditioned medium. Thus, the deposition of a rich extracellular matrix by living fibroblasts appeared necessary, but not sufficient to promote capillary-like formation. Fibroblasts seem to induce endothelial cells to spontaneously form CLT by secreting and organizing an abundant extracellular matrix, which creates a microenvironment around cells that could in turn trap growth factors produced by fibroblasts and promote three-dimensional cell organization.

Comparison between two classes of selective EP(3) antagonists and their biological activities.

Two different series of very potent and selective EP(3) antagonists have been reported: a novel series of ortho-substituted cinnamic acids [Belley, M., Gallant, M., Roy, B., Houde, K., Lachance, N., Labelle, M., Trimble, L., Chauret, N., Li, C., Sawyer, N., Tremblay, N., Lamontagne, S., Carrière, M.-C., Denis, D., Greig, G. M., Slipetz, D., Metters, K. M., Gordon, R., Chan, C. C., Zamboni, R. J. Bioorg. Med. Chem. Lett.2005, 15, 527] and the acylsulfonamides of ortho-(arylmethyl)cinnamates. [(a) Juteau, H., Gareau, Y., Labelle, M., Sturino, C. F., Sawyer, N., Tremblay, N., Lamontagne, S., Carrière, M.-C., Denis, D., Metters, K. M. Bioorg. Med. Chem. 2001, 9, 1977; (b) Juteau, H., Gareau, Y., Labelle, M., Lamontagne, S., Tremblay, N., Carrière, M.-C., Denis, D., Sawyer, N., Metters, K. M. Bioorg. Med. Chem. Lett.2001, 11, 747] The structural differences between the two series, along with their biological activity in vivo, in vitro, and metabolism, are analyzed. Some of those compounds, including hybrids containing the best structural features of both series, possess K(i) as low as 0.6 nM on the EP(3) receptor.

The genetic-environmental etiology of parents' perceptions and self-assessed behaviours toward their 5-month-old infants in a large twin and singleton sample.

BACKGROUND: Given the importance of parenting for the child's early socio-emotional development, parenting perceptions and behaviours, and their correlates, should be assessed as early as possible in the child's life. The goals of the present study were 1) to confirm, in two parallel population-based samples, including a large sample of twins, the factor structure of a new self-administered questionnaire assessing both parents' specific parenting perceptions and behaviours toward their 5-month-old infants (i.e., parental self-efficacy, perceived parental impact, parental hostile-reactive behaviours and parental overprotection), 2) to identify the specific risk factors associated with the negative side of these parenting dimensions, 3) to document the genetic-environmental etiology of these parenting dimensions through the twin method. METHODS: Parents (2,122 mothers and 1,829 fathers) of 5-month-old infants, and parents of 5-month-old infant twins (510 families) completed the questionnaire (28 items). The data were submitted to a series of confirmatory factor analyses. The contribution to parenting of a variety of risk factors was examined in the two samples using regression analyses. A series of quantitative genetic analyses were performed to quantify the different sources of variation in parenting. RESULTS: A consistent factor structure was found across informants and across samples. There were significant mean differences in parenting between mothers and fathers, as well as between parents of twins and parents of singletons. A differentiated pattern of association with risk factors was found for each dimension of parenting. The twin analyses revealed that shared environment accounted for each parenting dimension. Maternal hostile-reactive behaviours were also moderately related to genetic factors in the child and this association was mainly mediated by the infant difficultness. CONCLUSIONS: The overall pattern of results was consistent with Belsky's (1984) view of parenting as multiply determined. The longitudinal follow-up of these families should provide the means for testing developmental models about the determinants and outcomes of these parenting dimensions.

Structure-activity relationship studies on ortho-substituted cinnamic acids, a new class of selective EP(3) antagonists.

A series of novel ortho-substituted cinnamic acids have been synthesized, and their binding activity and selectivity on the four prostaglandin E(2) receptors evaluated. Many of them are very potent and selective EP(3) antagonists (K(i) 3-10 nM), while compound 9 is a very good and selective EP(2) agonist (K(i) 8 nM). The biological profile of the EP(2) agonist 9 in vivo and the metabolic profile of selected EP(3) antagonists are also reported.