11 research outputs found
Synthetic extracellular matrix mimic hydrogel improves efficacy of mesenchymal stromal cell therapy for ischemic cardiomyopathy.
No full textBACKGROUND:
Mesenchymal stromal cells (MSC) repair infarcted hearts mainly through paracrine mechanisms. Low cell engraftment limits the release of soluble paracrine factors (SF) over time and, consequently, MSC efficacy. We tested whether a synthetic extracellular matrix mimic, a hydrogel containing heparin (H-HG), could ameliorate MSC engraftment and binding/release of SF, thus improving MSC therapy efficacy.
METHODS AND RESULTS:
In vitro, rat bone-marrow MSC (rBM-MSC) were seeded and grown into H-HG. Under normoxia, the hydrogel did not affect cell survival (rBM-MSC survival >90% at each time point tested); vice versa, under hypoxia the biomaterial resulted to be protective for the cells (p < .001 vs rBM-MSC alone). H-HG or control PEG hydrogels (HG) were incubated with VEGF or bFGF for binding/release quantification. Data showed significantly higher amount of VEGF and bFGF bound by H-HG compared with HG (p < .05) and a constant release over time. In vivo, myocardial infarction (MI) was induced in female Sprague Dawley rats by permanent coronary ligation. One week later, saline, rBM-MSC, H-HG or rBM-MSC/H-HG were injected in the infarct zone. The co-injection of rBM-MSC/H-HG into infarcted hearts significantly increased cardiac function. Importantly, we observed a significant gain in MSC engraftment, reduction of ventricular remodeling and stimulation of neo-vasculogenesis. We also documented higher amounts of several pro-angiogenic factors in hearts treated with rBM-MSC/H-HG.
CONCLUSIONS:
Our data show that H-HG increases MSC engraftment, efficiently fine tunes the paracrine MSC actions and improves cardiac function in infarcted rat hearts.
STATEMENT OF SIGNIFICANCE:
Transplantation of MSC is a promising treatment for ischemic heart disease, but low cell engraftment has so far limited its efficacy. The enzymatically degradable H-HG that we developed is able to increase MSC retention/engraftment and, at the same time, to fine-tune the paracrine effects mediated by the cells. Most importantly, the co-transplantation of MSC and H-HG in a rat model of ischemic cardiomyopathy improved heart function through a significant reduction in ventricular remodeling/scarring and amelioration in neo-vasculogenesis/endogenous cardiac regeneration. These beneficial effects are comparable to those obtained by others using a much greater number of cells, strengthening the efficacy of the biomaterial used in increasing the therapeutic effects of MSC. Given its efficacy and safety, documented by the absence of immunoreaction, our strategy appears readily translatable to clinical scenarios
Simple silicone chamber system for 3D skeletal muscle tissue formation
No full textBioengineering skeletal muscle often requires customized equipment and intricate casting techniques. One of the major hurdles when initially trying to establish in vitro tissue engineered muscle constructs is the lack of consistency across published methodology. Although this diversity allows for specialisation according to specific research goals, lack of standardisation hampers comparative efforts. Differences in cell type, number and density, variability in matrix and scaffold usage as well as inconsistency in the distance between and type of adhesion posts complicates initial establishment of the technique with confidence. We describe an inexpensive, but readily adaptable silicone chamber system for the generation of skeletal muscle constructs that can readily be standardized and used to elucidate myoblast behaviour in a three-dimensional space. Muscle generation, regeneration and adaptation can also be investigated in this model, which is more advanced than differentiated myotubes
Dose-dependent modulation of myogenesis by HGF: implications for c-Met expression and downstream signalling pathways
No full text<div><p></p><p>Hepatocyte growth factor (HGF) regulates satellite cell activation, proliferation, and differentiation. We analyzed the dose-dependent effects of HGF on myogenesis. Murine C2C12 and human donor-derived skeletal muscle myoblasts were treated with 0, 2, or 10 ng/ml HGF followed by assessment of proliferation and differentiation. HGF (2 ng/ml) significantly promoted cell division, but reduced myogenic commitment and fusion. Conversely, 10 ng/ml HGF reduced proliferative capability, but increased differentiation. c-Met expression analysis revealed significantly <i>decreased</i> expression in differentiating cells cultured with 2 ng/ml HGF, but <i>increased</i> expression in proliferating cells with 10 ng/ml HGF. Mitogen-activated protein kinase (MAPKs: ERK, JNK, or p38K) and phosphatidylinositol-3-kinase (PI3K) inhibition abrogated the HGF-stimulated increase in cell number. Interestingly, PI3K and p38 kinase facilitated the negative effect of HGF on proliferation, while ERK inhibition abrogated the HGF-mediated decrease in differentiation. Dose-dependent effects of HGF are mediated by changes in c-Met expression and downstream MAPK and PI3K signalling.</p></div
Connecting theory and fiction: Margaret Atwood's novels and second wave feminism
No full textThis thesis undertakes an examination of the manner in which a novelist interacts with a contemporary theoretical discourse. I argue that the novelist and the theoretical discourse enter into a symbiotic relationship in which each influences and is influenced by the other. This process, I suggest, is simultaneous and complex. The thesis demonstrates how the prevailing theoretical discourse is absorbed by the contemporary author, is developed and redefined in conjunction with alternative concerns, and comes to permeate the narrative in an altered state. The novelist's new perspectives, frequently problematising theoretical claims, are then disseminated by the novel, promoting further discussion and development of the theoretical discourse. The thesis focuses on the novels of Margaret Atwood, considering them in relation to the history and development of second wave feminism. "Second wave feminism" is understood as an umbrella term that incorporates a wide variety of related but diverse and occasionally contradictory discourses, centring on the subjects of gender, femininity, and sexuality. The focus of the discussion is dual and presented simultaneously. Atwood's novels are analysed chronologically, and within the parameter of this analysis I demonstrate how her work has been influenced by earlier feminist theories, how it comments upon a variety of contemporary feminist ideas, and how it can be seen to anticipate further discussions within feminist discourse. Finally, I identify moments in Atwood's writing when alternative discourses compete with feminism to create new directions for feminist criticism. Examples of these discourses include Canadian nationalism, liberalism, communitarianism and environmentalism. The specificity of the novelist's interests and politics create a unique site of interaction for feminism which, I argue, benefits feminist theory by challenging, broadening and diversifying its focus. The thesis concludes that the symbiotic relationship of the theorist and the novelist is self-perpetuating and is also necessary and beneficial to both parties
Comparison of web-based information about cell-free DNA prenatal screening: implications for differences of sex development care
No full textObjectiveCell-free DNA (cfDNA) prenatal screening is a commercially available noninvasive test that detects fetal genetic material in maternal blood. While expectant parents often use it for “gender” determination, there is little information about unintended consequences of testing, such as revelation of a difference of sex development (DSD). The study aimed to characterize currently available website information about cfDNA and compare the cfDNA-related content.MethodsA systematic search for websites with information about cfDNA was conducted using search terms generated by a natural language processing analysis of the results of an Amazon Mechanical Turk (MTurk) survey of 1,000 parents and then performing a “Google” search, using the terms. Commercial cfDNA testing companies (CC) websites were also identified by consulting a genetic counselor (AGW). Data were collected on about each website’s characteristics and information about cfDNA. Information about cfDNA was compared between websites. Data were analyzed using descriptive statistics, Fisher’s exact test or Kruskal-Wallis test were applied, as appropriate.ResultsSixty websites were identified. After eliminating duplicates, 11 commercial company (CC) websites were identified. Nineteen other websites were reviewed of which six overlapped with five CC websites. Most of the websites had non-professional authors (73.7%), such as laypersons and CC representatives. CC websites were significantly more likely than search term-identified websites to state that cfDNA can screen for trisomy 21 (p=0.002), trisomy 18 (p<0.0001), trisomy 13 (p<0.001), sex chromosome aneuploidies (p<0.001), and microdeletions (p=0.002).ConclusionsThis study shows that most website currently available information for expectant parents about cfDNA prenatal screening is produced by non-professional organizations. There are significant differences between the information provided by CC and Google search websites, specifically about the number of conditions screened for by cfDNA. Improving availability and quality of information about cfDNA could improve counseling future expectant parents. Inclusion of information about the potential for detection of a DSD is needed
Improve safety, health, and environmental protection through the introduction of Six Sigma
No full textPlan BThe primary objective of this study was to evaluate the impact of implementation of a Six Sigma program on a company’s safety, health, and environmental protection performance. The review of literature included the evolution of safety health, and environmental protection; the evolution of management; the background of Six Sigma; the Six Sigma problem solving process; and the application of Six Sigma to safety health, and environmental protection. An interview guide was used to collect data related to the effects of the integration of Six Sigma on the safety, health, and environmental protection of the company. The findings resulting from the interview questions imply that Six Sigma can be effective in improving a company’s safety, health, and environmental protection. Finally, the paper offers some conclusions and recommendations concerning the connection we can make between Six Sigma and safety, health, and environmental protection. There is a connection we can make between Safety and Six Sigma. Six Sigma is a team-based approach to problem solving. Today’s safety professional should move beyond the standard reactive measurements of safety performance. Six Sigma provides the process for the development of a safety, health, and environmental protection performance measurement program by establishing well-defined performance measures, identifying all areas of performance, and documenting procedures for implementing the program
Tuning Tissue Ingrowth into Proangiogenic Hydrogels via Dual Modality Degradation
No full textThe
potential to control the rate of replacement of a biodegradable
implant by a tissue would be advantageous. Here, we demonstrate that
tissue invasion can be tuned through the novel approach of overlaying
an enzymatically degradable hydrogel with an increasingly hydrolytically
degradable environment. Poly(ethylene glycol) (PEG) hydrogels were
formed from varying proportions of PEG-vinyl sulfone and PEG-acrylate
(PEG-AC) monomers via a Michael-type addition reaction with a dithiol-containing
matrix-metalloproteinase-susceptible peptide cross-linker. Swelling
studies showed that PEG hydrogels with similar initial stiffnesses
degraded more rapidly as the PEG-AC content increased. The replacement
of subcutaneously implanted PEG hydrogels was also found to be proportional
to their PEG-AC content. In addition, it would in many instances be
desirable that these materials have the ability to stimulate their
neovascularization. These hydrogels contained covalently bound heparin,
and it was shown that a formulation of the hydrogel that allowed tissue
replacement to occur over 1 month could trap and release growth factors
and increase neovascularization by 50% over that time
Anger and assaultiveness of male forensic patients with developmental disabilities : links to volatile parents
No full textThis study with 107 male forensic patients with developmental disabilities investigated whether exposure to parental anger and aggression was related to anger and assaultiveness in a hospital, controlling for background variables. Patient anger and aggression were assessed by self-report, staff-ratings, and archival records. Exposure to parental anger/aggression, assessed by a clinical interview, was significantly related to patient self-reported anger, staff-rated anger and aggression, and physical assaults in hospital, controlling for age, intelligence quotient, length of hospital stay, violent offense history, and childhood physical abuse. Results are consonant with previous findings concerning detrimental effects of witnessing parental violence and with the theory on acquisition of cognitive scripts for aggression. Implications for clinical assessment and cognitive restructuring in anger treatment are discussed
A comparison of technology literacy between seventh and eighth grade students in a middle school technology education program
No full textPlan BTechnology education has a task at hand that is crucial, to create individuals that are technologically literate for the 21st century. Students involved in technology education classes have the opportunity of very diverse experiences. They work as teams to study problem–solving activities, learn about technological systems, use math, science, language arts and many skills to resolve issues that occur in the real world. It is our charge to be certain that all students gain the understanding necessary to thrive in the human made world. As early and often as they are exposed to technological concepts the better equipped they will be to live in our ever-changing society. The purpose of this study was to determine the technological concepts of seventh and eighth grade students at River Bluff Middle School. Those concepts were then measured against the Wisconsin Model Academic Standards and analyzed by gender. The students were a cluster grouping that took the class in both grades. All students used a pretest/posttest as an evaluation tool for the technology education class. By analyzing the results of this study the researcher realized the importance of how it can be utilized in the future for further study. The findings led to conclusions and recommendations for implementing ways to assess what our students should know and be able to do to become technologically literat
