With the increasing use of minimally invasive surgical techniques for intraocular pressure (IOP) lowering in glaucoma patients, there is a need to examine best practices regarding the postoperative ...management of these patients. Corticosteroids, though effective in controlling postoperative ocular pain and inflammation, present distinct challenges in glaucoma surgery patients, as their use can be associated with IOP elevation. Loteprednol etabonate (LE) is an ocular corticosteroid designed to have an improved safety profile relative to other corticosteroids.
We report here a representative selection of cases in which patients were successfully treated with LE ophthalmic gel 0.5% (LE gel) following a variety of minimally invasive glaucoma surgery (MIGS) procedures. Cases included patients undergoing various procedures including a Trabectome combined with cataract surgery; micro-stent surgery (iStent) combined with cataract surgery; supraciliary CyPass Micro-Stent placement combined with cataract surgery; Kahook Dual Blade goniotomy; and ab interno canaloplasty using the iTrack catheter.
In all cases, use of LE gel during the postoperative period appeared effective and safe in reducing inflammation and controlling pain. No adverse events or IOP elevations were noted, even in those patients continuing use of LE gel past the postoperative period for longer than six months with documented follow-up. In two cases, patients with elevated IOP using either prednisolone or difluprednate postoperatively were switched to LE gel, with a subsequent reduction in IOP.
This selection of cases involving patients undergoing MIGS suggests that LE gel may be an effective and safe option for treating postoperative inflammation and pain following such procedures with minimal to no effect on IOP or other negative sequalae.
This paper examines the emerging role of digital tools in a collaborative planning process for British Columbia's Bowen Island. The goal of this research was to evaluate the effectiveness of a ...‘digital workshop’, combining the interactive CommunityViz tool with the immersive lab facilities at the Collaborative for Advanced Landscape Planning (CALP). In support of the larger community planning process, two 3-h workshops were held at CALP's Landscape Immersion Lab. To facilitate collaborative exploration, the interactive landscape visualisation and real-time data analysis capabilities of CommunityViz were employed to illustrate the possible outcomes of residential density policies for Bowen Island's Snug Cove community. The community planning workshops were structured to provide the 14 semi-expert participants with the opportunity to explore and discuss the contentious residential density components of the draft Snug Cove Village Plan. The abilities to dynamically explore the visualisations of the planning proposals, and to see real-time changes in indicator metrics were considered particularly informative, and appeared to increase participants' understanding of the plan. Written and verbal responses indicated, however, that there was insufficient time to examine and interact with the information during the workshop, suggesting a need to examine in greater depth how and when these tools might best be employed in collaborative settings. Current and future research relating to this project is discussed.
Mass mortality events (MMEs) can remove up to 90% of individuals in a population and are especially damaging to population viability of long-lived species with slow life histories. Our goal was to ...elucidate the cause(s) of a MME of 53 Blanding’s Turtles (Emydoidea blandingii (Holbrook, 1838)), a globally endangered species, in a protected area. We investigated disease, winter-kill, and depredation as potential causes of the mortality. The turtle carcasses lacked soft tissue to test for disease, so we examined tissue from co-occurring live Leopard Frogs (Lithobates pipiens (Schreber, 1782)) and found no evidence of ranavirus, indicating that the disease was not present at our study site. Water temperature and dissolved aquatic oxygen at known overwintering sites and sites which yielded carcasses did not differ, suggesting that winter-kill did not cause the MME. Carcass condition, comparisons with descriptions of turtle depredation events in the literature, and trail cameras paired with turtle decoys identified potential predators within the study site and suggested that mass depredation, enabled by low water levels and a concomitant reduction in aquatic habitat, was the most likely cause of mortality. Our study can inform conservation of the study population and the management of MMEs of long-lived species elsewhere.
Asthma is an increasingly common disease that remains poorly understood and difficult to manage. This disease is characterized by airway hyperreactivity (AHR, defined by exaggerated airflow ...obstruction in response to bronchoconstrictors), mucus overproduction and chronic eosinophilic inflammation. AHR and mucus overproduction are consistently linked to asthma symptoms and morbidity. Asthma is mediated by Th2 lymphocytes, which produce a limited repertoire of cytokines, including interleukin-4 (IL-4), IL-5, IL-9 and IL-13. Although each of these cytokines has been implicated in asthma, IL-13 is now thought to be especially critical. In animal models of allergic asthma, blockade of IL-13 markedly inhibits allergen-induced AHR, mucus production and eosinophilia. Furthermore, IL-13 delivery to the airway causes all of these effects. IL-13 is thus both necessary and sufficient for experimental models of asthma. However, the IL-13-responsive cells causing these effects have not been identified. Here we show that mice lacking signal transducer and activator of transcription 6 (STAT6) were protected from all pulmonary effects of IL-13. Reconstitution of STAT6 only in epithelial cells was sufficient for IL-13-induced AHR and mucus production in the absence of inflammation, fibrosis or other lung pathology. These results demonstrate the importance of direct effects of IL-13 on epithelial cells in causing two central features of asthma.
For the last 500 years, the Americas have been a melting pot both for genetically diverse humans and for the pathogenic and commensal organisms associated with them. One such organism is the ...stomach-dwelling bacterium Helicobacter pylori, which is highly prevalent in Latin America where it is a major current public health challenge because of its strong association with gastric cancer. By analyzing the genome sequence of H. pylori isolated in North, Central and South America, we found evidence for admixture between H. pylori of European and African origin throughout the Americas, without substantial input from pre-Columbian (hspAmerind) bacteria. In the US, strains of African and European origin have remained genetically distinct, while in Colombia and Nicaragua, bottlenecks and rampant genetic exchange amongst isolates have led to the formation of national gene pools. We found three outer membrane proteins with atypical levels of Asian ancestry in American strains, as well as alleles that were nearly fixed specifically in South American isolates, suggesting a role for the ethnic makeup of hosts in the colonization of incoming strains. Our results show that new H. pylori subpopulations can rapidly arise, spread and adapt during times of demographic flux, and suggest that differences in transmission ecology between high and low prevalence areas may substantially affect the composition of bacterial populations.
Myofibroblasts are the major source of extracellular matrix components that accumulate during tissue fibrosis, and hepatic stellate cells (HSCs) are believed to be the major source of myofibroblasts ...in the liver. To date, robust systems to genetically manipulate these cells have not been developed. We report that Cre under control of the promoter of Pdgfrb (Pdgfrb-Cre) inactivates loxP-flanked genes in mouse HSCs with high efficiency. We used this system to delete the gene encoding α(v) integrin subunit because various α(v)-containing integrins have been suggested as central mediators of fibrosis in multiple organs. Such depletion protected mice from carbon tetrachloride-induced hepatic fibrosis, whereas global loss of β₃, β₅ or β₆ integrins or conditional loss of β₈ integrins in HSCs did not. We also found that Pdgfrb-Cre effectively targeted myofibroblasts in multiple organs, and depletion of the α(v) integrin subunit using this system was protective in other models of organ fibrosis, including pulmonary and renal fibrosis. Pharmacological blockade of α(v)-containing integrins by a small molecule (CWHM 12) attenuated both liver and lung fibrosis, including in a therapeutic manner. These data identify a core pathway that regulates fibrosis and suggest that pharmacological targeting of all α(v) integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases.
NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct ...measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products.
The molecular mechanisms of pulmonary fibrosis are poorly understood. We have used oligonucleotide arrays to analyze the gene expression programs that underlie pulmonary fibrosis in response to ...bleomycin, a drug that causes lung inflammation and fibrosis, in two strains of susceptible mice (129 and C57BL/6). We then compared the gene expression patterns in these mice with 129 mice carrying a null mutation in the epithelial-restricted integrin β 6 subunit (β 6-/-), which develop inflammation but are protected from pulmonary fibrosis. Cluster analysis identified two distinct groups of genes involved in the inflammatory and fibrotic responses. Analysis of gene expression at multiple time points after bleomycin administration revealed sequential induction of subsets of genes that characterize each response. The availability of this comprehensive data set should accelerate the development of more effective strategies for intervention at the various stages in the development of fibrotic diseases of the lungs and other organs.
This paper examines different binary mixtures of anionic/nonionic surfactants using a new technique known as solvent-free extrusion emulsification (SFEE) to control the surface charge in resulting ...nanosized polyester particles. Five similar nonionic surfactants with only minor structural differences from one another, along with an anionic surfactant (Calfax DB-45), were considered. The optimal hydrophilic end for the nonionic species was found to be 10–12 ethoxy units, whereas with respect to their hydrophobic end group, a more hindered branched alkyl structure was more desirable in preparing particles in the desired size range of 100–200 nm for this polymer. The preferred blend of Calfax/Igepal CA-630, found in a preliminary study, was shown to exhibit a synergistic interaction in SFEE in subsequent trials. The synergistic interaction was considered to arise from the high viscosity of the system, keeping the two surfactants partitioned across the interface of the emulsifying phases, which allowed a lower total surfactant concentration to be used than possible in a comparable solvent-based emulsification method. This partitioning across the interface decreased the nonextractable amount of Calfax left in the polyester latex. This approach of blending anionic and nonionic species shows an important step in preparing nanosized particles with controlled charge.
Objectives The goal of this study was to assess the prognostic significance of midwall and infarct patterns of late gadolinium enhancement (LGE) in aortic stenosis. Background Myocardial fibrosis ...occurs in aortic stenosis as part of the hypertrophic response. It can be detected by LGE, which is associated with an adverse prognosis in a range of other cardiac conditions. Methods Between January 2003 and October 2008, consecutive patients with moderate or severe aortic stenosis undergoing cardiovascular magnetic resonance with administration of gadolinium contrast were enrolled into a registry. Patients were categorized into absent, midwall, or infarct patterns of LGE by blinded independent observers. Patient follow-up was completed using patient questionnaires, source record data, and the National Strategic Tracing Service. Results A total of 143 patients (age 68 ± 14 years; 97 male) were followed up for 2.0 ± 1.4 years. Seventy-two underwent aortic valve replacement, and 27 died (24 cardiac, 3 sudden cardiac deaths). Compared with those with no LGE (n = 49), univariate analysis revealed that patients with midwall fibrosis (n = 54) had an 8-fold increase in all-cause mortality despite similar aortic stenosis severity and coronary artery disease burden. Patients with an infarct pattern (n = 40) had a 6-fold increase. Midwall fibrosis (hazard ratio: 5.35; 95% confidence interval: 1.16 to 24.56; p = 0.03) and ejection fraction (hazard ratio: 0.96; 95% confidence interval: 0.94 to 0.99; p = 0.01) were independent predictors of all-cause mortality by multivariate analysis. Conclusions Midwall fibrosis was an independent predictor of mortality in patients with moderate and severe aortic stenosis. It has incremental prognostic value to ejection fraction and may provide a useful method of risk stratification. (The Prognostic Significance of Fibrosis Detection in Cardiomyopathy; NCT00930735 )
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