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We emphasize the importance of the dissolution tests employing various bio-relevant media for better prediction of in vivo performance and the selection of a solid form for development.The Breast Cancer Resistance Protein (BCRP) is a key transporter in drug efflux and drug-drug interactions. However, endogenous expression of Multidrug Resistance Protein 1 (MDR1) confounds the interpretation of BCRP-mediated transport in in vitro models. Here we used a CRISPR-Cas9 edited Madin-Darby canine kidney (MDCK) II cell line (MDCKcMDR1-KO) for stable expression of human BCRP (hBCRP) with no endogenous canine MDR1 (cMDR1) expression (MDCK-hBCRPcMDR1-KO). Targeted quantitative proteomics verified expression of hBCRP, and global analysis of the entire proteome corroborated no or very low background expression of other drug transport proteins or metabolizing enzymes. This new cell line, had similar proteome like MDCKcMDR1-KO and a previously established, corresponding cell line overexpressing human MDR1 (hMDR1), MDCK-hMDR1cMDR1-KO. Functional studies with MDCK-hBCRPcMDR1-KO confirmed high hBCRP activity. The MDCK-hBCRPcMDR1-KO cell line together with the MDCK-hMDR1cMDR1-KO easily and accurately identified shared or specific substrates of the hBCRP and the hMDR1 transporters. These cell lines offer new, improved in vitro tools for the assessment of drug efflux and drug-drug interactions in drug development.A multiscale model by coupling computational fluid dynamics (CFD) with a discrete element model (DEM) and discrete droplet model (DDM) is developed to simulate a lab-scale Wurster coater. Two case studies are conducted to study the effect of particle shape in the system. In the first case study, 45,000 spherical particles are coated for 5 s while for the second case study, a mixture of 22,500 spherical particles and 22,500 cylindrical particles is simulated. The residence time distributions (RTD) of particles in different spray zones are compared, and the best spray zone is derived by analysing the positions of spray droplet-particle contacts. this website The simulation results show that the RTD of the particles within an accurate spray zone can provide valuable information on the final product's particles size distribution. Furthermore, the coefficient of variation (COV) for the coating mass received by the particles is studied for both case studies.
To investigate whether progressive macular ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) thinning are predictive for detecting visual field (VF) progression in eyes with high myopia.

Cohort study.

A total of 104 primary open-angle glaucoma (POAG) eyes with high myopia and 104 age- and VF severity-matched POAG eyes without high myopia (mean follow-up, 5.4 years) were included. High myopia was defined as a spherical equivalent <-6.0 diopters or axial length >26.5mm. Progressive GCIPL, RNFL, and VF deterioration were determined by Guided Progression Analysis (GPA) in optical coherence tomography and standard automated perimetry. The risk of VF progression was evaluated using Cox proportional hazard models.

Highly myopic eyes with progressive GCIPL thinning had a significantly higher risk of developing VF progression after adjusting for the baseline intraocular pressure (HR 4.00; P= .001) or peak intraocular pressure (HR 3.11; P= .011) in the multivariable Cox proportional hazard model, whereas highly myopic eyes with progressive RNFL thinning were not significantly associated with VF progression. In eyes without high myopia, both progressive GCIPL (HR 4.67 or 3.62; P= .008 or .037, respectively) and RNFL (HR 6.60 or 3.97; P= .001 or .016, respectively) thinning were associated with a significantly higher risk of developing VF progression after adjusting for the baseline or peak intraocular pressure.

Monitoring macular GCIPL thickness was effective for predicting glaucoma progression regardless of the presence of high myopia.
Monitoring macular GCIPL thickness was effective for predicting glaucoma progression regardless of the presence of high myopia.
To report 15-year incidence rate of visual loss (blindness and visual impairment [VI]), causes, and risk factors for participants in Andhra Pradesh Eye Disease Study III (APEDS III).

Population-based cohort study.

From 2012 to 2016, all rural participants were interviewed and underwent a comprehensive eye examination, including dilated fundus examination and imaging. Presenting visual acuity (PVA) and best-corrected visual acuity (BCVA) were measured using a standard logarithm of Minimum Angle of Resolution chart at 3 meters. World Health Organization (WHO) and United States of America (USA) categories of VI and blindness were used. Incident visual loss was defined as the development of or worsening of visual loss of one or more categories.

In APEDS I, 7,771 rural participants were examined using stratified, random-cluster systematic sampling; in APEDS III, 5,395 participants (69.4% of rural or 52.4% of total participants) were re-examined. Using WHO categories, the crude incidence rate of any visual loss based on PVA and BCVA were 14.6 (95% confidence interval [CI]13.6-15.7) and 6.3 (95% CI 6.1-6.4) per 100 person-years, respectively. Using USA criteria, the values were 22.6 (95% CI 22.3-23.0) and 10.6 (95% CI 10.3-10.8) per 100 person-years, respectively. More than 90% of visual loss was attributable to cataract and uncorrected refractive error. Using WHO categories, significant independent risk factors for the incident visual loss were increasing age, female gender, illiteracy, past or current smoker, and current use of alcohol. Using the USA definition, an additional risk factor was lower level of education.

The high incidence likely reflects poor access to eye care in this population, which needs to be taken into account when planning eye care programs.
The high incidence likely reflects poor access to eye care in this population, which needs to be taken into account when planning eye care programs.
The aim of this study was to determine the sociodemographic and risk factors for keratoconus (KC) patients with a nationwide Asian database.

Population-based matched case-control study.

We performed a secondary data analysis of the Taiwan National Health Insurance Research Database (NHIRD). Cases were patients with newly diagnosed KC in 1998-2015. Controls were patients without KC and matched 41 with the KC cases by age, sex, and index date. Comorbidities diagnosed before KC included diabetes mellitus (DM), asthma, allergic rhinitis, mitral valve prolapse, collagen vascular disease, aortic aneurysm, Down syndrome, sleep apnea, depression, hyperlipidemia, astigmatism, and myopia. Conditional logistic regression with forward selection were used to obtain risk factors for KC.

A total of 5,055 patients with KC were matched with 20,220 controls. The average age at KC first diagnosis was 29.76 years. Individuals who lived in suburban and rural area had lower odds ratio of KC (adjusted odds ratio [OR] 0.86, 95% confidence interval [CI] 0.
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