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Background: Low physical activity (PA) and fruit and vegetable (F&V) consumption in early childhood are continued public health challenges. This manuscript describes outcomes from two pilot studies for Sustainability via Active Garden Education (SAGE), a program designed to increase PA and F&V consumption among 3 to 5 year old children.

Methods: SAGE was

Background: Low physical activity (PA) and fruit and vegetable (F&V) consumption in early childhood are continued public health challenges. This manuscript describes outcomes from two pilot studies for Sustainability via Active Garden Education (SAGE), a program designed to increase PA and F&V consumption among 3 to 5 year old children.

Methods: SAGE was developed using community-based participatory research (CBPR) and delivered to children (N = 89) in early care and education centers (ECEC, N = 6) in two US cities. Children participated in 12 one-hour sessions that included songs, games, and interactive learning activities involving garden maintenance and taste tests. We evaluated reach, efficacy, adoption, implementation, and potential for maintenance of SAGE following the RE-AIM framework. Reach was evaluated by comparing demographic characteristics among SAGE participants and residents of target geographic areas. Efficacy was evaluated with accelerometer-measured PA, F&V consumption, and eating in the absence of hunger among children, parenting practices regarding PA, and home availability of F&V. Adoption was evaluated by the number of ECEC that participated relative to the number of ECEC that were recruited. Implementation was evaluated by completion rates of planned SAGE lessons and activities, and potential for maintenance was evaluated with a parent satisfaction survey.

Results: SAGE reached ECEC in neighborhoods representing a wide range of socioeconomic status, with participants’ sociodemographic characteristics representing those of the intervention areas. Children significantly increased PA during SAGE lessons compared to usual lessons, but they also consumed more calories in the absence of hunger in post- vs. pre-intervention tests (both p < .05). Parent reports did not suggest changes in F&V consumption, parenting PA practices, or home F&V availability, possibly due to low parent engagement. ECEC had moderate-to-high implementation of SAGE lessons and curriculum. Potential for maintenance was strong, with parents rating SAGE favorably and reporting increases in knowledge about PA and nutrition guidelines for young children.

Conclusions: SAGE successfully translated national PA guidelines to practice for young children but was less successful with nutrition guidelines. High adoption and implementation and favorable parent reports suggest high potential for program sustainability. Further work to engage parents and families of young children in ECEC-based PA and nutrition programming is needed.

Created2017-03-10
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Description

In vitro models that mimic in vivo host-pathogen interactions are needed to evaluate candidate drugs that inhibit bacterial virulence traits. We established a new approach to study Pseudomonas aeruginosa biofilm susceptibility on biotic surfaces, using a three-dimensional (3-D) lung epithelial cell model. P. aeruginosa formed antibiotic resistant biofilms on 3-D

In vitro models that mimic in vivo host-pathogen interactions are needed to evaluate candidate drugs that inhibit bacterial virulence traits. We established a new approach to study Pseudomonas aeruginosa biofilm susceptibility on biotic surfaces, using a three-dimensional (3-D) lung epithelial cell model. P. aeruginosa formed antibiotic resistant biofilms on 3-D cells without affecting cell viability. The biofilm-inhibitory activity of antibiotics and/or the anti-biofilm peptide DJK-5 were evaluated on 3-D cells compared to a plastic surface, in medium with and without fetal bovine serum (FBS). In both media, aminoglycosides were more efficacious in the 3-D cell model. In serum-free medium, most antibiotics (except polymyxins) showed enhanced efficacy when 3-D cells were present. In medium with FBS, colistin was less efficacious in the 3-D cell model. DJK-5 exerted potent inhibition of P. aeruginosa association with both substrates, only in serum-free medium. DJK-5 showed stronger inhibitory activity against P. aeruginosa associated with plastic compared to 3-D cells. The combined addition of tobramycin and DJK-5 exhibited more potent ability to inhibit P. aeruginosa association with both substrates. In conclusion, lung epithelial cells influence the efficacy of most antimicrobials against P. aeruginosa biofilm formation, which in turn depends on the presence or absence of FBS.

ContributorsCrabbe, Aurelie (Author) / Liu, Yulong (Author) / Matthijs, Nele (Author) / Rigole, Petra (Author) / De La Fuente-Nunez, Cesar (Author) / Davis, Richard (Author) / Ledesma, Maria (Author) / Sarker, Shameema (Author) / Van Houdt, Rob (Author) / Hancock, Robert E. W. (Author) / Coenye, Tom (Author) / Nickerson, Cheryl (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / Biodesign Institute (Contributor)
Created2017-03-03
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Description

Introduction: Fluorescence-guided surgery is one of the rapidly emerging methods of surgical “theranostics.” In this review, we summarize current fluorescence techniques used in neurosurgical practice for brain tumor patients as well as future applications of recent laboratory and translational studies.

Methods: Review of the literature.

Results: A wide spectrum of fluorophores that

Introduction: Fluorescence-guided surgery is one of the rapidly emerging methods of surgical “theranostics.” In this review, we summarize current fluorescence techniques used in neurosurgical practice for brain tumor patients as well as future applications of recent laboratory and translational studies.

Methods: Review of the literature.

Results: A wide spectrum of fluorophores that have been tested for brain surgery is reviewed. Beginning with a fluorescein sodium application in 1948 by Moore, fluorescence-guided brain tumor surgery is either routinely applied in some centers or is under active study in clinical trials. Besides the trinity of commonly used drugs (fluorescein sodium, 5-aminolevulinic acid, and indocyanine green), less studied fluorescent stains, such as tetracyclines, cancer-selective alkylphosphocholine analogs, cresyl violet, acridine orange, and acriflavine, can be used for rapid tumor detection and pathological tissue examination. Other emerging agents, such as activity-based probes and targeted molecular probes that can provide biomolecular specificity for surgical visualization and treatment, are reviewed. Furthermore, we review available engineering and optical solutions for fluorescent surgical visualization. Instruments for fluorescent-guided surgery are divided into wide-field imaging systems and hand-held probes. Recent advancements in quantitative fluorescence-guided surgery are discussed.

Conclusion: We are standing on the threshold of the era of marker-assisted tumor management. Innovations in the fields of surgical optics, computer image analysis, and molecular bioengineering are advancing fluorescence-guided tumor resection paradigms, leading to cell-level approaches to visualization and resection of brain tumors.

Created2016-10-17
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Despite serving as the primary entry portal for coxsackievirus B (CVB), little is known about CVB infection of the intestinal epithelium, owing at least in part to the lack of suitable in vivo models and the inability of cultured cells to recapitulate the complexity and structure associated with the gastrointestinal

Despite serving as the primary entry portal for coxsackievirus B (CVB), little is known about CVB infection of the intestinal epithelium, owing at least in part to the lack of suitable in vivo models and the inability of cultured cells to recapitulate the complexity and structure associated with the gastrointestinal (GI) tract. Here, we report on the development of a three-dimensional (3-D) organotypic cell culture model of Caco-2 cells to model CVB infection of the gastrointestinal epithelium. We show that Caco-2 cells grown in 3-D using the rotating wall vessel (RWV) bioreactor recapitulate many of the properties of the intestinal epithelium, including the formation of well-developed tight junctions, apical-basolateral polarity, brush borders, and multicellular complexity. In addition, transcriptome analyses using transcriptome sequencing (RNA-Seq) revealed the induction of a number of genes associated with intestinal epithelial differentiation and/or intestinal processes in vivo when Caco-2 cells were cultured in 3-D. Applying this model to CVB infection, we found that although the levels of intracellular virus production were similar in two-dimensional (2-D) and 3-D Caco-2 cell cultures, the release of infectious CVB was enhanced in 3-D cultures at early stages of infection. Unlike CVB, the replication of poliovirus (PV) was significantly reduced in 3-D Caco-2 cell cultures. Collectively, our studies show that Caco-2 cells grown in 3-D using the RWV bioreactor provide a cell culture model that structurally and transcriptionally represents key aspects of cells in the human GI tract and can thus be used to expand our understanding of enterovirus-host interactions in intestinal epithelial cells.

Created2015-11-18
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Description

In eutherians, the placenta acts as a barrier and conduit at the maternal-fetal interface. Syncytiotrophoblasts, the multinucleated cells that cover the placental villous tree surfaces of the human placenta, are directly bathed in maternal blood and are formed by the fusion of progenitor cytotrophoblasts that underlie them. Despite their crucial

In eutherians, the placenta acts as a barrier and conduit at the maternal-fetal interface. Syncytiotrophoblasts, the multinucleated cells that cover the placental villous tree surfaces of the human placenta, are directly bathed in maternal blood and are formed by the fusion of progenitor cytotrophoblasts that underlie them. Despite their crucial role in fetal protection, many of the events that govern trophoblast fusion and protection from microbial infection are unknown. We describe a three-dimensional (3D)–based culture model using human JEG-3 trophoblast cells that develop syncytiotrophoblast phenotypes when cocultured with human microvascular endothelial cells. JEG-3 cells cultured in this system exhibit enhanced fusogenic activity and morphological and secretory activities strikingly similar to those of primary human syncytiotrophoblasts. RNASeq analyses extend the observed functional similarities to the transcriptome, where we observed significant overlap between syncytiotrophoblast-specific genes and 3D JEG-3 cultures. Furthermore, JEG-3 cells cultured in 3D are resistant to infection by viruses and Toxoplasma gondii, which mimics the high resistance of syncytiotrophoblasts to microbial infections in vivo. Given that this system is genetically manipulatable, it provides a new platform to dissect the mechanisms involved in syncytiotrophoblast development and microbial resistance.

Created2016-03-04
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Description

Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions such as CNS B-cell lymphoma from operative lesions can be challenging, often necessitating immunohistochemical (IHC) procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific

Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions such as CNS B-cell lymphoma from operative lesions can be challenging, often necessitating immunohistochemical (IHC) procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific labeling using a novel lymphoma-specific fluorescent switchable aptamer. Our B-cell lymphoma-specific switchable aptamer produced only low-level fluorescence in its unbound conformation and generated an 8-fold increase in fluorescence once bound to its target on CD20-positive lymphoma cells. The aptamer demonstrated strong binding to B-cell lymphoma cells within 15 minutes of incubation as observed by flow cytometry. We applied the switchable aptamer to ex vivo xenograft tissue harboring B-cell lymphoma and astrocytoma, and within one hour specific visual identification of lymphoma was routinely possible. In this proof-of-concept study in human cell culture and orthotopic xenografts, we conclude that a fluorescent switchable aptamer can provide rapid and specific labeling of B-cell lymphoma, and that developing aptamer-based labeling approaches could simplify tissue staining and drastically reduce time to histopathological diagnoses compared with IHC-based methods. We propose that switchable aptamers could enhance expeditious, accurate intraoperative decision-making.

ContributorsGeorges, Joseph F. (Author) / Liu, Xiaowei (Author) / Eschbacher, Jennifer (Author) / Nichols, Joshua (Author) / Mooney, Michael A. (Author) / Joy, Anna (Author) / Spetzler, Robert F. (Author) / Feuerstein, Burt G. (Author) / Preul, Mark C. (Author) / Anderson, Trent (Author) / Yan, Hao (Author) / Nakaji, Peter (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / Biodesign Institute (Contributor)
Created2015-04-15
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Description

Background: Continuous monitoring technologies such as accelerometers and pedometers are the gold standard for physical activity (PA) measurement. However, inconsistencies in use, analysis, and reporting limit the understanding of dose–response relationships involving PA and the ability to make comparisons across studies and population subgroups. These issues are particularly detrimental to

Background: Continuous monitoring technologies such as accelerometers and pedometers are the gold standard for physical activity (PA) measurement. However, inconsistencies in use, analysis, and reporting limit the understanding of dose–response relationships involving PA and the ability to make comparisons across studies and population subgroups. These issues are particularly detrimental to the study of PA across different ethnicities with different PA habits. This systematic review examined the inclusion of published guidelines involving data collection, processing, and reporting among articles using accelerometers or pedometers in Hispanic or Latino populations.

Methods: English (PubMed; EbscoHost) and Spanish (SCIELO; Biblioteca Virtual en Salud) articles published between 2000 and 2013 using accelerometers or pedometers to measure PA among Hispanics or Latinos were identified through systematic literature searches. Of the 253 abstracts which were initially reviewed, 57 met eligibility criteria (44 accelerometer, 13 pedometer). Articles were coded and reviewed to evaluate compliance with recommended guidelines (N = 20), and the percentage of accelerometer and pedometer articles following each guideline were computed and reported.

Results: On average, 57.1 % of accelerometer and 62.2 % of pedometer articles reported each recommended guideline for data collection. Device manufacturer and model were reported most frequently, and provision of instructions for device wear in Spanish was reported least frequently. On average, 29.6 % of accelerometer articles reported each guideline for data processing. Definitions of an acceptable day for inclusion in analyses were reported most frequently, and definitions of an acceptable hour for inclusion in analyses were reported least frequently. On average, 18.8 % of accelerometer and 85.7 % of pedometer articles included each guideline for data reporting. Accelerometer articles most frequently included average number of valid days and least frequently included percentage of wear time.

Discussion: Inclusion of standard collection and reporting procedures in studies using continuous monitoring devices in Hispanic or Latino population is generally low.

ContributorsLayne, Charles S. (Author) / Parker, Nathan H. (Author) / Soltero, Erica G. (Author) / Rosales Chavez, Jose (Author) / O'Connor, Daniel P. (Author) / Gallagher, Martina R. (Author) / Lee, Rebecca (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-09-18
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Description

Strategies are needed to improve repopulation of decellularized lung scaffolds with stromal and functional epithelial cells. We demonstrate that decellularized mouse lungs recellularized in a dynamic low fluid shear suspension bioreactor, termed the rotating wall vessel (RWV), contained more cells with decreased apoptosis, increased proliferation and enhanced levels of total

Strategies are needed to improve repopulation of decellularized lung scaffolds with stromal and functional epithelial cells. We demonstrate that decellularized mouse lungs recellularized in a dynamic low fluid shear suspension bioreactor, termed the rotating wall vessel (RWV), contained more cells with decreased apoptosis, increased proliferation and enhanced levels of total RNA compared to static recellularization conditions. These results were observed with two relevant mouse cell types: bone marrow-derived mesenchymal stromal (stem) cells (MSCs) and alveolar type II cells (C10). In addition, MSCs cultured in decellularized lungs under static but not bioreactor conditions formed multilayered aggregates. Gene expression and immunohistochemical analyses suggested differentiation of MSCs into collagen I-producing fibroblast-like cells in the bioreactor, indicating enhanced potential for remodeling of the decellularized scaffold matrix. In conclusion, dynamic suspension culture is promising for enhancing repopulation of decellularized lungs, and could contribute to remodeling the extracellular matrix of the scaffolds with subsequent effects on differentiation and functionality of inoculated cells.

ContributorsCrabbe, Aurelie (Author) / Liu, Yulong (Author) / Sarker, Shameema (Author) / Bonenfant, Nicholas R. (Author) / Barrila, Jennifer (Author) / Borg, Zachary D. (Author) / Lee, James J. (Author) / Weiss, Daniel J. (Author) / Nickerson, Cheryl (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / Biodesign Institute (Contributor)
Created2015-05-11
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Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African American adults. African American men and women (n = 1467) completed

Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African American adults. African American men and women (n = 1467) completed questionnaires on the social environment, psychosocial factors (stress, depressive symptoms, and racial discrimination), and mental health. Multiple-mediator models were used to assess direct and indirect effects of the social environment on mental health. Low social status in the community (p < .001) and U.S. (p < .001) and low social support (p < .001) were associated with poor mental health. Psychosocial factors significantly jointly mediated the relationship between the social environment and mental health in multiple-mediator models. Low social status and social support were associated with greater perceived stress, depressive symptoms, and perceived racial discrimination, which were associated with poor mental health. Results suggest the relationship between the social environment and mental health is mediated by psychosocial factors and revealed potential mechanisms through which social status and social support influence the mental health of African American men and women. Findings from this study provide insight into the differential effects of stress, depression and discrimination on mental health. Ecological approaches that aim to improve the social environment and psychosocial mediators may enhance health-related quality of life and reduce health disparities in African Americans.

Created2016-04-27
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Extra-intestinal pathogenic E. coli (ExPEC), including avian pathogenic E. coli (APEC), pose a considerable threat to both human and animal health, with illness causing substantial economic loss. APEC strain χ7122 (O78∶K80∶H9), containing three large plasmids [pChi7122-1 (IncFIB/FIIA-FIC), pChi7122-2 (IncFII), and pChi7122-3 (IncI2)]; and a small plasmid pChi7122-4 (ColE2-like), has been

Extra-intestinal pathogenic E. coli (ExPEC), including avian pathogenic E. coli (APEC), pose a considerable threat to both human and animal health, with illness causing substantial economic loss. APEC strain χ7122 (O78∶K80∶H9), containing three large plasmids [pChi7122-1 (IncFIB/FIIA-FIC), pChi7122-2 (IncFII), and pChi7122-3 (IncI2)]; and a small plasmid pChi7122-4 (ColE2-like), has been used for many years as a model strain to study the molecular mechanisms of ExPEC pathogenicity and zoonotic potential. We previously sequenced and characterized the plasmid pChi7122-1 and determined its importance in systemic APEC infection; however the roles of the other pChi7122 plasmids were still ambiguous. Herein we present the sequence of the remaining pChi7122 plasmids, confirming that pChi7122-2 and pChi7122-3 encode an ABC iron transport system (eitABCD) and a putative type IV fimbriae respectively, whereas pChi7122-4 is a cryptic plasmid. New features were also identified, including a gene cluster on pChi7122-2 that is not present in other E. coli strains but is found in Salmonella serovars and is predicted to encode the sugars catabolic pathways. In vitro evaluation of the APEC χ7122 derivative strains with the three large plasmids, either individually or in combinations, provided new insights into the role of plasmids in biofilm formation, bile and acid tolerance, and the interaction of E. coli strains with 3-D cultures of intestinal epithelial cells. In this study, we show that the nature and combinations of plasmids, as well as the background of the host strains, have an effect on these phenomena. Our data reveal new insights into the role of extra-chromosomal sequences in fitness and diversity of ExPEC in their phenotypes.

ContributorsMellata, Melha (Author) / Maddux, Jacob (Author) / Nam, Timothy (Author) / Thomson, Nicholas (Author) / Hauser, Heidi (Author) / Stevens, Mark P. (Author) / Mukhopadhyay, Suman (Author) / Sarker, Shameema (Author) / Crabbe, Aurelie (Author) / Nickerson, Cheryl (Author) / Santander, Javier (Author) / Curtiss, Roy (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / Biodesign Institute (Contributor)
Created2012-01-04