Gestational Vulnerability to Ozone Air Pollution - A Placental Story

About 99% of the global population resides in areas with air pollution surpassing World Health Organization standards. Air pollution is associated with adverse neonatal health outcomes such as low fetal birth weight and an increased risk for maternal pre-eclampsia. A particularly reactive air pollutant is ozone, which forms reactive oxygen species that induce cellular damage. Research exists on the dispersion of reactive oxygen species through the bloodstream leading to fetal vulnerability during pregnancy, specifically via the placenta. Yet, placental and fetal development is a temporal process with varied susceptibility to negative gestational outcomes. To addressing this gap, our laboratory utilized non-targeted proteomic analysis of amniotic fluid collected at term after either gestational day (GD) 10 or GD20 ozone exposure. Results provided a comprehensive list of proteins that indicated distinct outcome phenotypes. The acute GD20 exposure resulted in a potent acute-phase increase in antioxidant factors while the subacute GD10 exposure had a greater influence of growth factors. In follow-up, selected markers of these phenotypes will be assessed within matched placentas. Relevant to the antioxidant GD20 response, we will assess superoxide dismutase 1 (SOD1) and catalase, which catalyze superoxide and hydrogen peroxide, respectively. Per the GD10 subacute response, connective tissue growth factor (CTGF) is produced by cells involved with structure and stabilization of the ECM and affects cellular growth, migration, adhesion, and vascularization. Together with CTGF, collagen T1A2 plays a vital role in the extracellular matrix (ECM) and has been linked to pregnancy complications such as miscarriage, gestational diabetes, and preeclampsia. To assess differential impacts on the placental vasculature, we will be investigating vascular endothelial cell adhesion molecule 1 (VCAM-1) and vascular endothelial cadherin (VE-Cadherin), which have both been identified as biomarkers of preeclampsia. In our experiments, pregnant Sprague-Dawley rats were exposed once to 0.3 ppm of ozone (O3) or filtered air (FA) via whole-body inhalation at GD10 or GD20 while control animals received a sham filtered air exposure at both times. Placentas were collected and snap-frozen at GD21 followed by thin-sectioning using a frozen microtome and formaldehyde fixation. Primary antibodies to our protein targets are incubated overnight at 4C followed by secondary alexa-fluor conjugated antibodies to allow for multi-channel immunofluorescence detection. Images are generated on a Zeiss Axio Imager.M2 microscope at 200x magnification. Ongoing experiments are set at optimizing primary antibody concentrations. The experimental design involves creating three wells of two sample placental tissues per slide that are prepared and marked with primary and then secondary antibodies specific to the protein of interest. Each well contains a different dilution of the antibody that yields different fluorescence. Densitometric analysis is used to determine the concentration with the greatest signal-to-noise ratio. Once optimized, antibodies will be co-imaged on placenta tissues across five replicate animal exposure per experimental group. Quantification of mean fluorescence intensity will then be tabulated across decidual, labyrinth and chorionic placental lamina. Results will be assessed using analysis of variance with post-hoc testing for group differences. Expected outcomes will demonstrate the relationship between prior amniotic fluid proteomic findings and effects within the placenta while differentiating placental vulnerability across windows of gestation. These findings will prove significant in understanding outcomes at term for both the mother and fetus when exposed to ozone pollution.https://scholarscompass.vcu.edu/uresposters/1432/thumbnail.jp

Female sterility associated with increased clonal propagation suggests a unique combination of androdioecy and asexual reproduction in populations of Cardamine amara (Brassicaceae)

Background and Aims The coexistence of hermaphrodites and female-sterile individuals, or androdioecy, has been documented in only a handful of plants and animals. This study reports its existence in the plant species Cardamine amara (Brassicaceae), in which female-sterile individuals have shorter pistils than seed-producing hermaphrodites. Methods Morphological analysis, in situ manual pollination, microsatellite genotyping and differential gene expression analysis using Arabidopsis microarrays were used to delimit variation between female-sterile individuals and hermaphrodites. Key Results Female sterility in C. amara appears to be caused by disrupted ovule development. It was associated with a 2.4- to 2.9-fold increase in clonal propagation. This made the pollen number of female-sterile genets more than double that of hermaphrodite genets, which fulfils a condition of co-existence predicted by simple androdioecy theories. When female-sterile individuals were observed in wild androdioecious populations, their ramet frequencies ranged from 5 to 54%; however, their genet frequencies ranged from 11 to 29%, which is consistent with the theoretically predicted upper limit of 50%. Conclusions The results suggest that a combination of sexual reproduction and increased asexual proliferation by female-sterile individuals probably explains the invasion and maintenance of female sterility in otherwise hermaphroditic populations. To our knowledge, this is the first report of the coexistence of female sterility and hermaphrodites in the Brassicacea

Uncertainty in land-use adaptation persists despite crop model projections showing lower impacts under high warming

Climate change is expected to impact crop yields and alter resource availability. However, the understanding of the potential of agricultural land-use adaptation and its costs under climate warming is limited. Here, we use a global land system model to assess land-use-based adaptation and its cost under a set of crop model projections, including CO2 fertilization, based on climate model outputs. In our simulations of a low-emissions scenario, the land system responds through slight changes in cropland area in 2100, with costs close to zero. For a high emissions scenario and impacts uncertainty, the response tends toward cropland area changes and investments in technology, with average adaptation costs between −1.5 and +19 US$05 per ton of dry matter per year. Land-use adaptation can reduce adverse climate effects and use favorable changes, like local gains in crop yields. However, variance among high-emissions impact projections creates challenges for effective adaptation planning

Predictors of patient satisfaction with hospital health care

BACKGROUND: We used a validated inpatient satisfaction questionnaire to evaluate the health care received by patients admitted to several hospitals. This questionnaire was factored into distinct domains, creating a score for each to assist in the analysis. We evaluated possible predictors of patient satisfaction in relation to socio-demographic variables, history of admission, and survey logistics. METHODS: Cross-sectional study of patients discharged from four acute care general hospitals. Random sample of 650 discharged patients from the medical and surgical wards of each hospital during February and March 2002. A total of 1,910 patients responded to the questionnaire (73.5%). Patient satisfaction was measured by a validated questionnaire with six domains: information, human care, comfort, visiting, intimacy, and cleanliness. Each domain was scored from 0 to 100, with higher scores indicating higher levels of patient satisfaction. RESULTS: In the univariate analysis, age was related to all domains except visiting; gender to comfort, visiting, and intimacy; level of education to comfort and cleanliness; marital status to information, human care, intimacy, and cleanliness; length of hospital stay to visiting and cleanliness, and previous admissions to human care, comfort, and cleanliness. The timing of the response to the mailing and who completed the questionnaire were related to all variables except visiting and cleanliness. Multivariate analysis confirmed in most cases the previous findings and added additional correlations for level of education (visiting and intimacy) and marital status (comfort and visiting). CONCLUSION: These results confirm the varying importance of some socio-demographic variables and length of stay, previous admission, the timing of response to the questionnaire, and who completed the questionnaire on some aspects of patient satisfaction after hospitalization. All these variables should be considered when evaluating patient satisfaction

Identification of a gene signature in cell cycle pathway for breast cancer prognosis using gene expression profiling data

<p>Abstract</p> <p>Background</p> <p>Numerous studies have used microarrays to identify gene signatures for predicting cancer patient clinical outcome and responses to chemotherapy. However, the potential impact of gene expression profiling in cancer diagnosis, prognosis and development of personalized treatment may not be fully exploited due to the lack of consensus gene signatures and poor understanding of the underlying molecular mechanisms.</p> <p>Methods</p> <p>We developed a novel approach to derive gene signatures for breast cancer prognosis in the context of known biological pathways. Using unsupervised methods, cancer patients were separated into distinct groups based on gene expression patterns in one of the following pathways: apoptosis, cell cycle, angiogenesis, metastasis, p53, DNA repair, and several receptor-mediated signaling pathways including chemokines, EGF, FGF, HIF, MAP kinase, JAK and NF-κB. The survival probabilities were then compared between the patient groups to determine if differential gene expression in a specific pathway is correlated with differential survival.</p> <p>Results</p> <p>Our results revealed expression of cell cycle genes is strongly predictive of breast cancer outcomes. We further confirmed this observation by building a cell cycle gene signature model using supervised methods. Validated in multiple independent datasets, the cell cycle gene signature is a more accurate predictor for breast cancer clinical outcome than the previously identified Amsterdam 70-gene signature that has been developed into a FDA approved clinical test MammaPrint^®.</p> <p>Conclusion</p> <p>Taken together, the gene expression signature model we developed from well defined pathways is not only a consistently powerful prognosticator but also mechanistically linked to cancer biology. Our approach provides an alternative to the current methodology of identifying gene expression markers for cancer prognosis and drug responses using the whole genome gene expression data.</p

Tumor Blood Flow Differs between Mouse Strains: Consequences for Vasoresponse to Photodynamic Therapy

Fluctuations in tumor blood flow are common and attributed to factors such as vasomotion or local vascular structure, yet, because vessel structure and physiology are host-derived, animal strain of tumor propagation may further determine blood flow characteristics. In the present report, baseline and stress-altered tumor hemodynamics as a function of murine strain were studied using radiation-induced fibrosacomas (RIF) grown in C3H or nude mice. Fluctuations in tumor blood flow during one hour of baseline monitoring or during vascular stress induced by photodynamic therapy (PDT) were measured by diffuse correlation spectroscopy. Baseline monitoring revealed fluctuating tumor blood flow highly correlated with heart rate and with similar median periods (i.e., ∼9 and 14 min in C3H and nudes, respectively). However, tumor blood flow in C3H animals was more sensitive to physiologic or stress-induced perturbations. Specifically, PDT-induced vascular insults produced greater decreases in blood flow in the tumors of C3H versus nude mice; similarly, during baseline monitoring, fluctuations in blood flow were more regular and more prevalent within the tumors of C3H mice versus nude mice; finally, the vasoconstrictor L-NNA reduced tumor blood flow in C3H mice but did not affect tumor blood flow in nudes. Underlying differences in vascular structure, such as smaller tumor blood vessels in C3H versus nude animals, may contribute to strain-dependent variation in vascular function. These data thus identify clear effects of mouse strain on tumor hemodynamics with consequences to PDT and potentially other vascular-mediated therapies

Pathogenesis and Host Response in Syrian Hamsters following Intranasal Infection with Andes Virus

Hantavirus pulmonary syndrome (HPS), also referred to as hantavirus cardiopulmonary syndrome (HCPS), is a rare but frequently fatal disease caused by New World hantaviruses. In humans HPS is associated with severe pulmonary edema and cardiogenic shock; however, the pathogenesis of this disease remains unclear largely due to a lack of suitable animal models for the study of disease progression. In this study we monitored clinical, virological, pathophysiological parameters and host immunological responses to decipher pathological factors and events in the lethal Syrian hamster model of HPS following intranasal inoculation of Andes virus. Transcriptional profiling of the host gene responses demonstrated a suppression of innate immune responses in most organs analyzed during the early stage of infection, except for in the lung which had low level activation of several pro-inflammatory genes. During this phase Andes virus established a systemic infection in hamsters, with viral antigen readily detectable in the endothelium of the majority of tissues analyzed by 7–8 days post-inoculation. Despite wide-spread infection, histological analysis confirmed pathological abnormalities were almost exclusively found in the lungs. Immediately preceding clinical signs of disease, intense activation of pro-inflammatory and Th1/Th2 responses were observed in the lungs as well as the heart, but not in peripheral organs, suggesting that localized immune-modulations by infection is paramount to pathogenesis. Throughout the course of infection a strong suppression of regulatory T-cell responses was noted and is hypothesized to be the basis of the aberrant immune activations. The unique and comprehensive monitoring of host immune responses to hantavirus infection increases our understanding of the immuno-pathogenesis of HPS and will facilitate the development of treatment strategies targeting deleterious host immunological responses

Investigating organizational quality improvement systems, patient empowerment, organizational culture, professional involvement and the quality of care in European hospitals: the 'Deepening our Understanding of Quality Improvement in Europe (DUQuE)' project

BACKGROUND: Hospitals in European countries apply a wide range of quality improvement strategies. Knowledge of the effectiveness of these strategies, implemented as part of an overall hospital quality improvement system, is limited. METHODS/DESIGN: We propose to study the relationships among organisational quality improvement systems, patient empowerment, organisational culture, professionals' involvement with the quality of hospital care, including clinical effectiveness, patient safety and patient involvement. We will employ a cross-sectional, multi-level study design in which patient-level measurements are nested in hospital departments, which are in turn nested in hospitals in different EU countries. Mixed methods will be used for data collection, measurement and analysis. Hospital/care pathway level constructs that will be assessed include external pressure, hospital governance, quality improvement system, patient empowerment in quality improvement, organisational culture and professional involvement. These constructs will be assessed using questionnaires. Patient-level constructs include clinical effectiveness, patient safety and patient involvement, and will be assessed using audit of patient records, routine data and patient surveys. For the assessment of hospital and pathway level constructs we will collect data from randomly selected hospitals in eight countries. For a sample of hospitals in each country we will carry out additional data collection at patient-level related to four conditions (stroke, acute myocardial infarction, hip fracture and delivery). In addition, structural components of quality improvement systems will be assessed using visits by experienced external assessors. Data analysis will include descriptive statistics and graphical representations and methods for data reduction, classification techniques and psychometric analysis, before moving to bi-variate and multivariate analysis. The latter will be conducted at hospital and multilevel. In addition, we will apply sophisticated methodological elements such as the use of causal diagrams, outcome modelling, double robust estimation and detailed sensitivity analysis or multiple bias analyses to assess the impact of the various sources of bias. DISCUSSION: Products of the project will include a catalogue of instruments and tools that can be used to build departmental or hospital quality and safety programme and an appraisal scheme to assess the maturity of the quality improvement system for use by hospitals and by purchasers to contract hospitals

The James Webb Space Telescope Mission: Optical Telescope Element Design, Development, and Performance

The James Webb Space Telescope (JWST) is a large, infrared space telescope that has recently started its science program which will enable breakthroughs in astrophysics and planetary science. Notably, JWST will provide the very first observations of the earliest luminous objects in the Universe and start a new era of exoplanet atmospheric characterization. This transformative science is enabled by a 6.6 m telescope that is passively cooled with a 5-layer sunshield. The primary mirror is comprised of 18 controllable, low areal density hexagonal segments, that were aligned and phased relative to each other in orbit using innovative image-based wavefront sensing and control algorithms. This revolutionary telescope took more than two decades to develop with a widely distributed team across engineering disciplines. We present an overview of the telescope requirements, architecture, development, superb on-orbit performance, and lessons learned. JWST successfully demonstrates a segmented aperture space telescope and establishes a path to building even larger space telescopes.Comment: accepted by PASP for JWST Overview Special Issue; 34 pages, 25 figure

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29