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Thus, curcumin reduced colistin MIC well below the CLSI breakpoint ( less then 2 μg/ml). Curcumin also exhibited synergy with colistin against most of the clinical isolates of Enterobacteriaceae tested. Efficiency of Col + Sal + CUR was evident in time kill curve analysis, which displayed a 6 log and a 4 log decline in CFU/ml by 24 h in U3790 and BC936 strains respectively. In vivo intramuscular fish infection studies showed that the triad combination reduced the bacterial bioburden of E. coli U3790 by 2.6 log and that of K. pneumoniae BC936 by 1.6 log. Hence, our study shows the efficacy of inhibiting MarR by salicylate and inhibiting efflux pump with curcumin restores colistin sensitivity in colistin resistant Enterobacteriaceae in vitro and in vivo.Hydrogels used in regenerative medicine are often designed to allow cellular infiltration, degradation, and neovascularization. Low molecular weight hydrogels (LMWHs), formed by self-assembly via non-covalent interactions, are gaining significant interest because they are soft, easy to use and injectable. We propose LMWHs as suitable body implant materials that can stimulate tissue regeneration. We produced four new LMWHs with molecular entities containing nucleic acid and lipid building blocks and analyzed the foreign body response upon subcutaneous implantation into mice. Despite being infiltrated with macrophages, none of the hydrogels triggered detrimental inflammatory responses. selleck Most macrophages present in the hydrogel-surrounding tissue acquired an immuno-modulatory rather than inflammatory phenotype. Concomitantly, no fibrotic capsule was formed after three weeks. Our glyconucleolipid LMWHs exhibited different degradation kinetics in vivo and in vitro. LMWHs with high angiogenic properties in vivo, werng the surrounding tissues. The resulting gels aim at forming scaffolds that the host cells colonize without major inflammation, and that won't be insulated by a strong fibrosis reaction. Importantly, their molecular degradation releases a product (a glycosyl-nucleoside conjugate) promoting angiogenesis. In this sense, these LMWH represent an important advance in the development of biomaterials promoting tissue regeneration.Cell therapy to restore cardiac function in chronic heart failure has been extensively studied. However, its therapeutic value is limited due to poor cell engraftment and survival and the therapeutic outcomes have been attributed to paracrine secretions such as extracellular vesicles (EV). The direct use of EV is an attractive therapeutic strategy and it has been shown that the kinetics of delivery of the EV to the targeted tissue may impact the outcomes. However, there are currently no technologies to deliver EV to the heart in a controlled and tunable manner. The objective of this study was to design a controlled release system, based on a photocurable adhesive polymer, to locally deliver EV to the cardiac tissue. We have first demonstrated that the adhesive polymer, PGSA-g-EG, did not impact the EV bioactivity in vitro and was biocompatible in vivo when tested in a rat model. Importantly, the polymer remained attached to the heart surface for at least 1 month. We have then evaluated and optimized the in viable manner, EV to the heart. The present study describes the use of PGSA-g-EG polymer as an adhesive cardiac patch with potential to enable the controlled delivery of bioactive EV over an extended period of time to the cardiac tissue.Ocular inflammation is one of the leading causes of blindness worldwide, and steroids in topical ophthalmic solutions (e.g. dexamethasone eye drops) are the mainstay of therapy for ocular inflammation. For many non-infectious ocular inflammatory diseases, such as uveitis, eye drops are administered as often as once every hour. The high frequency of administration coupled with the side effects of eye drops leads to poor adherence for patients. Drug-eluting contact lenses have long been sought as a potentially superior alternative for sustained ocular drug delivery; but loading sufficient drug into contact lenses and control the release of the drug is still a challenge. A dexamethasone releasing contact lens (Dex-Lens) was previously developed by encapsulating a dexamethasone-polymer film within the periphery of a hydrogel-based contact lens. Here, we demonstrate safety and efficacy of the Dex-Lens in rabbit models in the treatment of anterior ocular inflammation. The Dex-Lens delivered drug for 7 days in vivo . Ocular inflammation is normally treated by steroid eye drops. Depending on the type and severity of inflammation, patients may have to take drops every hour for days at a time. Such severe dosing regimen can lead to patients missing doses. Also, more than 95% drug in an eye drop never goes inside the eye. Here we present a contact lens that release a steroid (dexamethasone) for seven days at a time. It is much more efficient than eye drops and a significant improvement since once worn, the patient will avoid missing doses.In reverse osmosis desalination, the concentrate is a saline solution that may become supersaturated. Heterogeneous nucleation of salts occurs at the membrane surface, resulting in the buildup of inorganic deposits on the membrane. The inorganic nucleation process, however, is complex in natural waters. Most studies focused primarily on single salt fouling of membranes, and related treatment for single solute systems. However, scale formation, especially gypsum, is affected by the presence of different salts and metals. In this wok, for the first time, we investigate the mixed precipitation of iron oxides and gypsum. The role of citric acid in the inhibition of precipitation was studied for different concentrations in both the absence and the presence of Fe2+. Conductivity and ion concentration measurements were used to estimate the formation time of gypsum. Scanning electron microscopy, X-Ray Diffraction (XDR) analysis, and Infra-Red spectroscopy analysis were used to provide structural information. Collected data showed that the presence of Fe2+ accelerates gypsum precipitation and shortens its induction time. Analytic results showed that gypsum crystals are greatly affected by the presence of Fe2+ ions, which generated needle shaped crystals. Citric acid can delay the induction time of gypsum precipitation. It also affects the morphology of gypsum crystals through adsorption mechanism. XDR diagrams revealed that the presence of citric acid (20 mg/L) can stabilize the bassanite phase (CaSO4·½H2O) for much longer periods. In the presence of Fe2+ ions, citric acid extends the induction time of calcium sulfate and minimizes the acceleration effect of Fe2+ ions. SEM images showed that the presence of ferrous ions during the chemical inhibition generates the β-hemihydrate form of calcium sulfate.Quantification of PM2.5 exposure and associated mortality is critical to inform policy making. Previous studies estimated varying PM2.5-related mortality in China due to the usage of different source data, but rarely justify the data selection. To quantify the sensitivity of mortality assessment to source data, we first constructed state-of-the-art PM2.5 predictions during 2000-2018 at a 1-km resolution with an ensemble machine learning model that filled missing data explicitly. We also calibrated and fused various gridded population data with a geostatistical method. Then we assessed the PM2.5-related mortality with various PM2.5 predictions, population distributions, exposure-response functions, and baseline mortalities. We found that in addition to the well documented uncertainties in the exposure-response functions, missingness in PM2.5 prediction, PM2.5 prediction error, and prediction error in population distribution resulted to a 40.5%, 25.2% and 15.9% lower mortality assessment compared to the mortality assessed with the best-performed source data, respectively. With the best-performed source data, we estimated a total of approximately 25 million PM2.5-related mortality during 2001-2017 in China. From 2001 to 2017, The PM2.5 variations, growth and aging of population, decrease in baseline mortality led to a 7.8% increase, a 42.0% increase and a 24.6% decrease in PM2.5-related mortality, separately. We showed that with the strict clean air policies implemented in 2013, the population-weighted PM2.5 concentration decreased remarkably at an annual rate of 4.5 μg/m3, leading to a decrease of 179 thousand PM2.5-related deaths nationwide during 2013-2017. The mortality decrease due to PM2.5 reduction was offset by the population growth and aging population.Prymnesium parvum continues to spread globally, producing harmful algal blooms that release toxins known to cause fish kills. While previous work has identified possible P. parvum toxin(s) (e.g., prymnesins, fatty acids, fatty acid amides) and investigated treatment strategies targeted at minimizing cell abundance, studies examining efficacy of treatment approaches to remove toxins are lacking. To understand influences of sunlight on toxins stability and toxicity to fish, acutely toxic P. parvum cultures were exposed to three light scenarios (lab dark control, field dark, and field light) and then evaluated for acute toxicity to fish and prymnesins abundance. Previous work showed acute toxicity to fathead minnow larvae was ameliorated after 2 h of sunlight exposure, and results observed herein found an identical trend. Acute toxicity disappeared in light exposed filtrate, but filtrate exposed to 35 °C without sunlight remained acutely toxic to fish. Additionally, six prymnesins were identified through high-resolution mass spectrometry and abundance corresponded to acute toxicity levels. Prymnesins were present at the highest level in filtrate that was acutely toxic but diminished in filtrate that was exposed to light and correspondingly ameliorated acute toxicity to fish. These findings suggest prymnesins are responsible for measured acute toxicity and are photo-labile, which represents an important implication for treatment strategies.Polycyclic aromatic hydrocarbons (PAHs) inhalation bioaccessibility was assessed in 65 atmospheric particulate matter samples (PM10) collected at an Atlantic coastal European urban site. The proposed method consists on a physiologically based extraction (PBET) by using Gamble's solution followed by a vortex assisted liquid-liquid micro-extraction (VALLME) and quantification by high performance liquid chromatography with fluorescence detection (HPLC-FLD). The use of a micro-extraction technique combined with FLD detection, provides a simple, fast, sensitive, accurate and low-cost methodology to PAHs quantification in bioaccessible fractions. Accuracy of the bioaccessibility study was assessed by means of a mass balance approaches using a PM10 filter and a certified reference material (ERM-CZ100). High-moderate inhalation bioaccessibilities were found for phenanthrene (Phe), fluoranthene (Ft) and pyrene (Pyr) (average ratios in the 52-65% range); while dibenz (a,h)anthracene (DBahA), indeno (1,2,3-cd)pyrene (IP) and benzo (g,h,i)perylene (BghiP) were observed to be less bioaccessibles (average ratios in the 11-14% range). Relationship between PM10 composition (major ions, trace metals, equivalent black carbon (eBC) and UV-absorbing particulate matter (UVPM)) and PAHs bioaccessibility ratios was also assessed. Principal Component Analysis (PCA) showed that PAHs bioaccessibility percentage is dependent on anthropogenic (eBC, UVPM and Sb concentrations) and marine sources of PM10. Predicted PAHs bioaccessibilities after applying a multiple linear regression model based on marine and anthropogenic source of PM10 could also be established. Health risk assessment of target PM10-associated PAHs via inhalation was assessed considering bioaccessibility concentrations by using hazard index (HI) and BaP equivalent concentration (BaPeq) approaches, suggesting no carcinogenic risk in the area during the sampling campaign.

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