Evaluación de microcápsulas de ácido acetilsalicílico preparadas con eftalato de acetilcelulosa, etilcelulosa o sus mezclas, mediante una técnica de adición de emulsión no disolvente

El ácido acetilsalicílico (AAS) se encapsuló con eftalato de acetilcelulosa (EAC), etilcelulosa (EC) o sus mezclasmediante un método de adición de emulsión no disolvente. Se evaluaron los perfiles de liberación de AAS enmicrocápsulas preparadas en diversas proporciones de fármaco y polímero (10:1 y 4:1) y microcápsulas en comprimidosen un pH 1,2 ó 6. Los resultados mostraron que al reducir la proporción de fármaco respecto al polímero sereducía la velocidad de liberación. Las microcápsulas preparadas con EC presentaron el índice de liberación másbajo. Los estudios de liberación in vitro indicaron que la velocidad de liberación del fármaco disminuía tras lapreparación del comprimido, debido a la formación de una matriz no desintegrable. La liberación de AAS en un pH6 es significativamente mayor en todas las microcápsulas, incluso si se utiliza EC, que no es hidrosoluble. Esto sedebe probablemente a la mayor solubilidad del AAS en un pH 6, lo que indica la formación incompleta de la películaalrededor de las partículas de AAS. Los datos de liberación se examinaron cinéticamente y se calcularon los modelosideales para la liberación del fármaco. Los resultados mostraron que en las microcápsulas en comprimidos elcoeficiente de correlación más elevado se obtuvo con la liberación de orden cero. En las microcápsulas en comprimidosque contenían EAC o una mezcla de EAC y EC, la contribución de la erosión fue mayor que en las microcápsulasque no estaban en comprimidos

Evaluation of microcapsules of acetyl salicylic acid prepared with cellulose acetate phthalate, ethycellulose or their mixtures by an emulsion non-solvent addition technique

El ácido acetilsalicílico (AAS) se encapsuló con eftalato de acetilcelulosa (EAC), etilcelulosa (EC) o sus mezclas mediante un método de adición de emulsión no disolvente. Se evaluaron los perfiles de liberación de AAS en microcápsulas preparadas en diversas proporciones de fármaco y polímero (10:1 y 4:1) y microcápsulas en comprimidos en un pH 1,2 ó 6. Los resultados mostraron que al reducir la proporción de fármaco respecto al polímero se reducía la velocidad de liberación. Las microcápsulas preparadas con EC presentaron el índice de liberación más bajo. Los estudios de liberación in vitro indicaron que la velocidad de liberación del fármaco disminuía tras la preparación del comprimido, debido a la formación de una matriz no desintegrable. La liberación de AAS en un pH 6 es significativamente mayor en todas las microcápsulas, incluso si se utiliza EC, que no es hidrosoluble. Esto se debe probablemente a la mayor solubilidad del AAS en un pH 6, lo que indica la formación incompleta de la película alrededor de las partículas de AAS. Los datos de liberación se examinaron cinéticamente y se calcularon los modelos ideales para la liberación del fármaco. Los resultados mostraron que en las microcápsulas en comprimidos el coeficiente de correlación más elevado se obtuvo con la liberación de orden cero. En las microcápsulas en comprimidos que contenían EAC o una mezcla de EAC y EC, la contribución de la erosión fue mayor que en las microcápsulas que no estaban en comprimidos.Acetyl salicylic acid (ASA) was encapsulated with cellulose acetate phthalate (CAP), ethylcellulose (EC) or their mixtures by an emulsion non-solvent addition method. The release profiles of ASA from prepared microcapsules with different ratios of drug to polymer (10:1 and 4:1) and tableted microcapsules were evaluated at pH 1.2 or 6. The results showed that a reduction in the ratio of drug to polymer resulted in a reduction in release rate. The microcapsules prepared with EC showed the lowest release rate. The in vitro release studies showed that the drug release rate decreased after tableting, because of the formation of a non-disintegrating matrix. Release of ASA at pH 6 is significantly higher in all microcapsules, even when using EC which is not water soluble. This is probably due to higher solubility of ASA at pH 6 indicating incomplete film formation around the ASA particles. Release data were examined kinetically and the ideal kinetic models were estimated for drug release. The results showed that for tableted microcapsules the highest correlation coefficient was achieved with the zero-order release. For tableted microcapsules containing CAP or the mixture of CAP and EC contribution of erosion was higher than that of untableted microcapsules

Decision making under incompleteness based on soft set theory

[EN]Decision making with complete and accurate information is ideal but infrequent. Unfortunately, in most cases the available infor- mation is vague, imprecise, uncertain or unknown. The theory of soft sets provides an appropriate framework for decision making that may be used to deal with uncertain decisions. The aim of this paper is to propose and analyze an effective algorithm for multiple attribute decision-making based on soft set theory in an incomplete information environment, when the distribution of incomplete data is unknown. This procedure provides an accurate solution through a combinatorial study of possible cases in the unknown data. Our theoretical development is complemented by practical examples that show the feasibility and implementability of this algorithm. Moreover, we review recent research on decision making from the standpoint of the theory of soft sets under incomplete information

Increasing access to integrated ESKD care as part of Universal Health Coverage

The global nephrology community recognizes the need for a cohesive strategy to address the growing problem of end-stage kidney disease (ESKD). In March 2018, the International Society of Nephrology hosted a summit on integrated ESKD care, including 92 individuals from around the globe with diverse expertise and professional backgrounds. The attendees were from 41 countries, including 16 participants from 11 low- and lower-middle–income countries. The purpose was to develop a strategic plan to improve worldwide access to integrated ESKD care, by identifying and prioritizing key activities across 8 themes: (i) estimates of ESKD burden and treatment coverage, (ii) advocacy, (iii) education and training/workforce, (iv) financing/funding models, (v) ethics, (vi) dialysis, (vii) transplantation, and (viii) conservative care. Action plans with prioritized lists of goals, activities, and key deliverables, and an overarching performance framework were developed for each theme. Examples of these key deliverables include improved data availability, integration of core registry measures and analysis to inform development of health care policy; a framework for advocacy; improved and continued stakeholder engagement; improved workforce training; equitable, efficient, and cost-effective funding models; greater understanding and greater application of ethical principles in practice and policy; definition and application of standards for safe and sustainable dialysis treatment and a set of measurable quality parameters; and integration of dialysis, transplantation, and comprehensive conservative care as ESKD treatment options within the context of overall health priorities. Intended users of the action plans include clinicians, patients and their families, scientists, industry partners, government decision makers, and advocacy organizations. Implementation of this integrated and comprehensive plan is intended to improve quality and access to care and thereby reduce serious health-related suffering of adults and children affected by ESKD worldwide

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Characterization of polysulfone/diisopropylamine 1-alkyl-3-methylimidazolium ionic liquid membranes: high pressure gas separation applications

Membrane separation is gaining great attention in many applications, especially in gas separation. Polysulfone (PSF) is the most widely studied polymeric membrane material for CO2 in its pure or modified state. Ionic liquids supported membrane technology (SILMs) are now widely applied due to their unique properties at room temperatures. In our previous study, we proved the enhanced ability of ionic liquid enhanced PSF for the separation of CO2 from gas streams. In this study, the dielectric measurements (BDS) extending up to 107 Hz for different concentrations of ionic liquid into PSF matrix, are presented. Thermogravimetric analysis measurement (TGA), differential scanning calorimeter (DSC), dynamic mechanical analysis, and the tensile properties of the membranes are studied in order to optimize the efficiency of separating CO2 from CO2/N2 mixture and CO2/CH4. TGA showed that pure PSF is a highly thermostable polymer, of which the 5% weight loss temperature is above 150 C. DSC traces show that the Tg of PSF was 149.5 C and decreases gradually for the composites. This behavior was confirmed with BDS analyses, which also revealed important information about the chain motions dynamics and the fragility index.Qatar Foundation;Qatar National Research FundScopu