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Thus, our results demonstrate that this partially humanized AgxtD205N rat strain is a high-performing model of primary hyperoxaluria type 1 for understanding pathology, and the development of novel therapeutics, such as reprogramming of the metabolic pathway through genome editing.Randomised Controlled Trials (RCTs) are considered the gold-standard for evaluating the effectiveness of interventions. However, criticisms of traditional designs are that they can be inefficient, inflexible, expensive and conducted in a manner disconnected from real-life clinical practice. Novel strategies and approaches are being utilised to overcome these limitations including comprehensive consumer engagement, core outcome sets, novel trial designs, streamlined data collection, cost-effectiveness and return on investment evaluations, knowledge dissemination plans and impact evaluation. These strategies can be implemented at the design, conduct, implementation and dissemination stages of the trial process. This review aims to provide an overview of these strategies and approaches to improve the relevance, efficiency, effectiveness and impact of nephrology research.Immunosuppression in IgA nephropathy (IgAN) should be reserved for patients at high-risk of disease progression, which KDIGO guidelines determine based solely on proteinuria 1g or more/day. To investigate if treatment decisions can be more accurately accomplished using individualized risk from the International IgAN Prediction Tool, we simulated allocation of a hypothetical immunosuppression therapy in an international cohort of adults with IgAN. Two decision rules for treatment were applied based on proteinuria 1g or more/day or predicted risk from the Prediction Tool above a threshold probability. An appropriate decision was defined as immunosuppression allocated to patients experiencing the primary outcome (50% decline in eGFR or ESKD) and withheld otherwise. The net benefit and net reduction in treatment are the proportion of patients appropriately allocated to receive or withhold immunosuppression, adjusted for the harm from inappropriate decisions, calculated for all threshold probabilities from 0-100%. Of 3299 patients followed for 5.1 years, 522 (15.8%) experienced the primary outcome. Treatment allocation based solely on proteinuria οϕ 1g or more/day had a negative net benefit (was harmful) because immunosuppression was increasingly allocated to patients without progressive disease. Compared to using proteinuria, treatment allocation using the Prediction Tool had a larger net benefit up to 23.4% (95% confidence interval 21.5-25.2%) and a larger net reduction in treatment up to 35.1% (32.3-37.8%). IAP inhibitor Thus, allocation of immunosuppression to high-risk patients with IgAN can be substantially improved using the Prediction Tool compared to using proteinuria.The polysaccharides from Ophiopogon japonicus (OJPs) were known to have protective effects against diabetes, and cardiovascular and chronic inflammatory diseases. However, OJPs were poorly absorbed after oral administration, resulting in limited efficacy because of the low bioavailability. In this study, OJPs extracted and fractionated from Ophiopogon japonicus were used to prepare OJPs/chitosan (CS)/whey protein (WP) co-assembled nanoparticles. The OJPs/CS/WP nanoparticles showed high biocompatibility and inhibited the cytotoxicity of RAW264.7 cells induced by nickel. With the assistance of CS and WP, the anti-inflammatory and antioxidant activities of OJPs were enhanced because the nanoparticles improved OJPs uptake by RAW264.7 macrophage cells as evidenced by efficient scavenging of DPPH and ABTS free radicals and effective inhibition of NO production and the gene expressions of iNOS, COX2, TNF-α, CCL2, and CXCL2 inflammatory signals. Determining the transepithelial electrical resistance and paracellular permeability of Caco-2 monolayer/macrophage co-cultured system suggested that the OJPs-loaded nanoparticles effectively protected the intestinal epithelial barrier integrity against the damage caused by LPS-stimulated macrophage inflammation and attenuated the defects of intestinal epithelial TJ barrier and permeability. These findings suggest that the OJPs/CS/WP nanoparticles may be potential carriers for oral delivery of OJPs to treat intestinal barrier defects, such as inflammatory bowel disease (IBD).The advent of liposome technology with its unique features has led researchers to work relentlessly on the successful development of novel drug delivery vehicles based on liposomes. But still there are some limitations of using liposomes for biomedical applications because of their poor stability that is primarily the cause of rapid leakage of drugs incorporated within the said matrices. Therefore, a considerable interest has been paid on modification of surface of liposomes by combining it with several compounds of interest. Although chitosan-liposome based systems are not yet well-documented. Hence, in this review, we exclusively focused on the discussion about the preparation of various chitosan-liposome based systems and their suitable biomedical applications as well.An active chitosan-based film, blended with the hydrolysable tannin-rich extract obtained from fibrous chestnut wood (Castanea sativa Mill.), underwent a simultaneous engineering optimization in terms of measured moisture content (MC), tensile strength (TS), elongation at break (EB), and total phenolic content (TPC). The optimal product formulation for a homogeneous film-forming solution was sought by designing an empirical Box-Behnken model simulation, based on three independent variables the concentrations of chitosan (1.5-2.0% (w/v)), extracted powder-form chestnut extract (0.5-1.0% (w/v)) and plasticizer glycerol (30.0-90.0% (w/w); determined per mass of polysaccharide). Obtained linear (MC), quadratic (TS or EB), and two-factor interaction (TPC) sets were found to be significant (p less then 0.05), to fit well with characteristic experimental data (0.969 less then R2 less then 0.992), and could be considered predictive. Although all system parameters were influential, the level of polyol played a vital continuous role in defining EB, MC, and TS, while the variation of the chestnut extract caused an expected connected change in affecting TPC.
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