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Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. Antibody expression and assembly were compared with CHO-derived antibodies by SDS-PAGE, western blotting, size-exclusion chromatography and LC-MS peptide mapping. N-linked glycosylation was assessed by rapid fluorescence/mass spectrometry and LC-ESI-MS. Susceptibility to gastric digestion was assessed in an in vitro model. Bcl 2 inhibitor Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. SIgA1 assembly appeared superior to SIgA2 in plants. Both sub-classes exhibited resistance to degradation by simulated gastric fluid, comparable to CHO-produced 68-61 SIgA1. The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. The plant-derived SIgA2 mAb demonstrated protection against diarrhea in a murine infection model. Although antibody yield and purification need to be optimized, anti-ETEC SIgA antibodies produced in a low-cost plant platform are functionally equivalent to CHO antibodies, and provide promise for passive immunotherapy in LMICs.Background and purpose - Orthopedic surgery is one of the specialties with most compensation claims. We assessed the claims following knee arthroplasty surgery reported to the Norwegian System of Patient Injury Compensation (NPE) in light of institutional procedure volume.Patients and methods - We collected data from NPE and the Norwegian Arthroplasty Register (NAR) for the study period (2008-2018). Age, sex, type of claim, and reason for compensation were collected from NPE, while the number of arthroplasty surgeries was collected from NAR. The treating hospitals were grouped by quartiles according to annual procedure volume. The effect of hospital volume on the likelihood of an accepted claim was estimated.Results - NAR received 64,241 reports of arthroplasty procedures, of which 572 (0.9%) patients filed a claim for treatment injury. 55% of the claims were accepted, representing 0.5% of all knee arthroplasties. The most common reason for accepted claim was a hospital-acquired infection, in 28% of the patients, followed by misplaced implant (26%) and aseptic loosening (13%). The hospitals with the lowest annual volume (57 or fewer arthroplasties per year, first quarter) had a statistically significantly larger fraction of granted claims per procedures compared with other institutions.Interpretation - The overall risk of ending up with compensation due to treatment error following knee arthroplasty was 0.5%. The risk of accepted claim was greater for patients operated in the lowest volume hospitals.
Performance-based risk-sharing agreements (PBRSAs), between payers, health care providers, and technology manufacturers can be useful when there is uncertainty about the (cost-) effectiveness of a new technology or service. However, they can be challenging to design and implement.
A total of 18 performance-based agreements were identified through a literature review. All but two of the agreements identified were pay-for-performance schemes, agreed between providers and payers at the national level. No examples were found of agreements between health care providers and manufacturers at the local level. The potential for these local agreements was illustrated by hypothetical case studies of water quality management and an integrated chronic kidney disease program.
Performance-based risk-sharing agreements can work to the advantage of patients, health care providers, payers, and technology manufacturers, particularly if they facilitate the introduction of technologies or systems of care that might not have been introduced otherwise. However, the design, conduct, and implementation of PBRSAs in renal care pose a number of challenges. Efforts should be made to overcome these challenges so that more renal care patients can benefit from technological advances and new models of care.
Performance-based risk-sharing agreements can work to the advantage of patients, health care providers, payers, and technology manufacturers, particularly if they facilitate the introduction of technologies or systems of care that might not have been introduced otherwise. However, the design, conduct, and implementation of PBRSAs in renal care pose a number of challenges. Efforts should be made to overcome these challenges so that more renal care patients can benefit from technological advances and new models of care.Crude glycerol, a by-product of biodiesel production, was employed as the carbon source to produce lipase using Pichia pastoris. Under identical fermentation conditions, cell growth and lipase activity were improved using crude glycerol instead of pure glycerol. The impacts of crude glycerol impurities (methyl ester, grease, glycerol, methanol, and metal ions Na+, Ca2+, and Fe3+) on lipase production were investigated. Impurities accelerated P. pastoris entering the stationary phase. Na+, Ca2+, and grease in waste crude glycerol were the main factors influencing higher lipase activity. Through response surface optimization of Ca2+, Na+, and grease concentrations, lipase activity reached 1437 U/mL (15,977 U/mg), which was 2.5 times that of the control. This study highlights the economical and highly efficient valorization of crude glycerol, demonstrating its possible utilization as a carbon source to produce lipase by P. pastoris without pretreatment.
Polysaccharide-based biomaterials are extensively used in wound care healing due to their unique liquid absorption, gelling properties and biocompatibility properties. They play an important role in controlling infections of highly exuding hard-to-heal wounds. The main objective of this study was to develop silver-containing polysaccharide-based tricomponent antibacterial fibres for use in these complex wounds.
The fibres were developed by coating silver-containing alginate and psyllium fibres with hydrolysed chitosan. Dope solution containing alginate, psyllium and silver carbonate was extruded into a coagulation bath containing calcium chloride and hydrolysed chitosan. The developed fibres were tested for liquid absorption, swelling and antibacterial properties against a control fibre (of alginate and psyllium).
The developed fibres showed comparatively better liquid absorption, gelling and antibacterial properties than the control fibres.
The study concluded that developed fibres could be a preferred choice for application on hard-to-heal wounds with high levels of exudate, to support infection control and faster healing.
Read More: https://www.selleckchem.com/Bcl-2.html
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