Impact of alginate-producing Pseudomonas aeruginosa on alveolar macrophage apoptotic cell clearance

Pseudomonas aeruginosa infection is a hallmark of lung disease in cystic fibrosis. Acute infection with P. aeruginosa profoundly inhibits alveolar macrophage clearance of apoptotic cells (efferocytosis) via direct effect of virulence factors. During chronic infection, P. aeruginosa evades host defense by decreased virulence, which includes the production or, in the case of mucoidy, overproduction of alginate. The impact of alginate on innate immunity, in particular on macrophage clearance of apoptotic cells is not known. We hypothesized that P. aeruginosa strains that exhibit reduced virulence impair macrophage clearance of apoptotic cells and we investigated if the polysaccharide alginate produced by mucoid P. aeruginosa is sufficient to inhibit alveolar macrophage efferocytosis. Rat alveolar or human peripheral blood monocyte (THP-1)-derived macrophage cell lines were exposed in vitro to exogenous alginate or to wild type or alginate-overproducing mucoid P. aeruginosa prior to challenge with apoptotic human Jurkat T-lymphocytes. The importance of LPS contamination and that of structural integrity of alginate polymers was tested using alginate of different purities and alginate lyase, respectively. Alginate inhibited alveolar macrophage efferocytosis in a dose- and time-dependent manner. This effect was augmented but not exclusively attributed to lipopolysaccharide (LPS) present in alginates. Alginate-producing P. aeruginosa inhibited macrophage efferocytosis by more than 50%. A mannuronic-specific alginate lyase did not restore efferocytosis inhibited by exogenous guluronic-rich marine alginate, but had a marked beneficial effect on efferocytosis of alveolar macrophages exposed to mucoid P. aeruginosa. Despite decreased virulence, mucoid P. aeruginosa may contribute to chronic airway inflammation through significant inhibition of alveolar clearance of apoptotic cells and debris. The mechanism by which mucoid bacteria inhibit efferocytosis may involve alginate production and synergy with LPS, suggesting that alginate lyase may be an attractive therapeutic approach to airway inflammation in cystic fibrosis and other chronic obstructive pulmonary diseases characterized by P. aeruginosa colonization

Moderate Exercise Attenuates Lipopolysaccharide-induced Inflammation And Associated Maternal And Fetal Morbidities In Pregnant Rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fetal growth restriction (FGR) and coagulopathies are often associated with aberrant maternal inflammation. Moderate-intensity exercise during pregnancy has been shown to increase utero-placental blood flow and to enhance fetal nutrition as well as fetal and placental growth. Furthermore, exercise is known to reduce inflammation. To evaluate the effect of moderate-intensity exercise on inflammation associated with the development of maternal coagulopathies and FGR, Wistar rats were subjected to an exercise regime before and during pregnancy. To model inflammation-induced FGR, pregnant rats were administered daily intraperitoneal injections of E. coli lipopolysaccharide (LPS) on gestational days (GD) 13.5-16.5 and sacrificed at GD 17.5. Control rats were injected with saline. Maternal hemostasis was assessed by thromboelastography. Moderate-intensity exercise prevented LPS-mediated increases in white blood cell counts measured on GD 17.5 and improved maternal hemostasis profiles. Importantly, our data reveal that exercise prevented LPS-induced FGR. Moderate-intensity exercise initiated before and maintained during pregnancy may decrease the severity of maternal and perinatal complications associated with abnormal maternal inflammation.114Canadian Bureau for International Education - Department of Foreign Affairs and International Trade (CBIE/DFAIT)Coordination for the Improvement of Higher Education Personnel-The Ministry of Education of Brazil (CAPES/MEC)FAEPEX (University of Campinas)Canadian Institutes of Health Research (CIHR) [MOP 119496]Canadian Haemophilia SocietyCIHR Doctoral Award-Frederick Banting and Charles Best Canada Graduate ScholarshipOntario Graduate ScholarshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Preparation And Evaluation Of Atenolol-Β-Cyclodextrin Orally Disintegrating Tablets Using Co-Process Crospovidone-Sodium Starch Glycolate

Objective: The aim of this current research was to formulate and analyze the characteristics of atenolol-p-cyclodextrin which using co-process crospovidone-sodium starch glycolate as the disintegrants. Evaluation which has been conducted on orally disintegrating tablets consist of wetting time, water absorption ratio, in vitro dispersion time, and dissolution. Methods: Inclusion complex of atenolol-p-cyclodextrin which were prepared using solvent evaporation method, then formulated using co-processed crospovidone-sodium starch glycolate 1:1 (formula 1) and 1 :2 (formula 2) into orally disintegrating tablets by direct compression technique. Orally disintegrating tablets of atenolol-P-cyclodextrin using a physical mixture of crospovidone-sodium starch glycolate 1:1 (formula 3), 1:2 (formula 4) was also prepared as a control. The prepared formulations (Fl-F4) were evaluated by several parameters such as wetting time, water absorption ratio, in vitro dispersion time, and dissolution. Results: Orally disintegrating tablets of atenolol P-cyclodextrin using co-processed crospovidone-sodium starch glycolate 1:1 (formula 1) showed shorter wetting time (53.53 ± 2.26 seconds) and in vitro dispersion time (47.44 ± 2.49 seconds) compare to the other formulas. Formula 1 also exhibited the highest dissolution efficiency compare to the formula which was used in the physical mixture. The results of this study also revealed that there was a high correlation between in vitro dispersion time and dissolution efficiency of atenolol-p-cyclodextrin orally disintegrating tablets. Conclusion: Orally disintegrating tablets of atenolol- P-cyclodextrin showed enhanced dissolution efficiency due to the presence of inclusion complex and co-processed crospovidonesodium starch glycolate. Formula 1 was found to be the best formula in this study. This formula effectively reduces in vitro dispersion time, hence the dissolution efficiency became higher

\u3ci\u3eIn Vitro\u3c/i\u3e Validation of Finite Element Analysis of Blood Flow in Deformable Models

The purpose of this article is to validate numerical simulations of flow and pressure incorporating deformable walls using in vitro flow phantoms under physiological flow and pressure conditions. We constructed two deformable flow phantoms mimicking a normal and a restricted thoracic aorta, and used a Windkessel model at the outlet boundary. We acquired flow and pressure data in the phantom while it operated under physiological conditions. Next, in silico numerical simulations were performed, and velocities, flows, and pressures in the in silico simulations were compared to those measured in the in vitro phantoms. The experimental measurements and simulated results of pressure and flow waveform shapes and magnitudes compared favorably at all of the different measurement locations in the two deformable phantoms. The average difference between measured and simulated flow and pressure was approximately 3.5 cc/s (13% of mean) and 1.5 mmHg (1.8% of mean), respectively. Velocity patterns also showed good qualitative agreement between experiment and simulation especially in regions with less complex flow patterns. We demonstrated the capabilities of numerical simulations incorporating deformable walls to capture both the vessel wall motion and wave propagation by accurately predicting the changes in the flow and pressure waveforms at various locations down the length of the deformable flow phantoms

California\u27s Coast and Ocean Summary Report, part of California\u27s Fourth Climate Change Assessment

This report synthesizes current scientific understanding about the impacts of climate change on California’s coast and ocean and presents a forward-looking summary of challenges and opportunities for the future. It is one component of California’s Fourth Climate Change Assessment (Fourth Assessment). To prepare this report, the state called upon the California Ocean Protection Council (OPC) and California Ocean Science Trust (OST) to convene an Ocean Protection Council Science Advisory Team (OPC-SAT) working group composed of science and policy leaders. Similar to other components of the Fourth Assessment, the 12-member working group was guided by an Advisory Group of end users and high-level decision-makers. This report is intended to provide accessible scientific information that is relevant for policy and decision-makers, build a foundation for policy to address climate change impacts through adaptation and mitigation, highlight best practices and models for coastal adaptation to climate change along the coast, and inform interested members of the public on the impacts of climate change on California’s coast and ocean waters and potential approaches for adaptation and mitigation. It will also inform the next update of the Safeguarding California plan, a policy document serving as California’s climate adaptation strategy, by presenting a scientific grounding to help focus and prioritize future state adaptation efforts

The Crystal Structure of H-2Dd MHC Class I Complexed with the HIV-1-Derived Peptide P18-I10 at 2.4 Å Resolution Implications for T Cell and NK Cell Recognition

AbstractThe structure of H-2Dd complexed with the HIV-derived peptide P18-I10 (RGPGRAFVTI) has been determined by X-ray crystallography at 2.4 Å resolution. This MHC class I molecule has an unusual binding motif with four anchor residues in the peptide (G2, P3, R/K/H5, and I/L/F9 or 10). The cleft architecture of H-2Dd includes a deep narrow passage accomodating the N-terminal part of the peptide, explaining the obligatory G2P3 anchor motif. Toward the C-terminal half of the peptide, p5R to p8V form a type I′ reverse turn; residues p6A to p9T, and in particular p7F, are readily exposed. The structure is discussed in relation to functional data available for T cell and natural killer cell recognition of the H-2Dd molecule

Trends and emissions of six perfluorocarbons in the Northern Hemisphere and Southern Hemisphere

Perfluorocarbons (PFCs) are potent greenhouse gases with global warming potentials up to several thousand times greater than CO2 on a 100-year time horizon. The lack of any significant sinks for PFCs means that they have long atmospheric lifetimes of the order of thousands of years. Anthropogenic production is thought to be the only source for most PFCs. Here we report an update on the global atmospheric abundances of the following PFCs, most of which have for the first time been analytically separated according to their isomers: c-octafluorobutane (c-C4F8), n-decafluorobutane (n-C4F10), n-dodecafluoropentane (n-C5F12), n-tetradecafluorohexane (n-C6F14), and n-hexadecafluoroheptane (n-C7F16). Additionally, we report the first data set on the atmospheric mixing ratios of perfluoro-2-methylpentane (i-C6F14). The existence and significance of PFC isomers have not been reported before, due to the analytical challenges of separating them. The time series spans a period from 1978 to the present. Several data sets are used to investigate temporal and spatial trends of these PFCs: time series of air samples collected at Cape Grim, Australia, from 1978 to the start of 2018; a time series of air samples collected between July 2015 and April 2017 at Tacolneston, UK; and intensive campaign-based sampling collections from Taiwan. Although the remote “background” Southern Hemispheric Cape Grim time series indicates that recent growth rates of most of these PFCs are lower than in the 1990s, we continue to see significantly increasing mixing ratios that are between 6 % and 27 % higher by the end of 2017 compared to abundances measured in 2010. Air samples from Tacolneston show a positive offset in PFC mixing ratios compared to the Southern Hemisphere baseline. The highest mixing ratios and variability are seen in air samples from Taiwan, which is therefore likely situated much closer to PFC sources, confirming predominantly Northern Hemispheric emissions for most PFCs. Even though these PFCs occur in the atmosphere at levels of parts per trillion molar or less, their total cumulative global emissions translate into 833 million metric tonnes of CO2 equivalent by the end of 2017, 23 % of which has been emitted since 2010. Almost two-thirds of the CO2 equivalent emissions within the last decade are attributable to c-C4F8, which currently also has the highest emission rates that continue to grow. Sources of all PFCs covered in this work remain poorly constrained and reported emissions in global databases do not account for the abundances found in the atmosphere

The Health Equity Promotion Model: Reconceptualization of Lesbian, Gay, Bisexual, and Transgender (LGBT) Health Disparities

National health initiatives emphasize the importance of eliminating health disparities among historically disadvantaged populations. Yet, few studies have examined the range of health outcomes among lesbian, gay, bisexual, and transgender (LGBT) people. To stimulate more inclusive research in the area, we present the Health Equity Promotion Model—a framework oriented toward LGBT people reaching their full mental and physical health potential that considers both positive and adverse health-related circumstances. The model highlights (a) heterogeneity and intersectionality within LGBT communities; (b) the influence of structural and environmental context; and (c) both health-promoting and adverse pathways that encompass behavioral, social, psychological, and biological processes. It also expands upon earlier conceptualizations of sexual minority health by integrating a life course development perspective within the health-promotion model. By explicating the important role of agency and resilience as well as the deleterious effect of social structures on health outcomes, it supports policy and social justice to advance health and well-being in these communities. Important directions for future research as well as implications for health-promotion interventions and policies are offered