Dapsone is an important medication for the treatment of leprosy, but a life-threatening drug hypersensitivity syndrome develops in some patients. In this report from China, an
HLA-B
locus is ...identified as a strong genetic risk factor for the syndrome.
Dapsone (4-4′-sulfonyldianiline), which was first synthesized in 1908,
1
is both an antibiotic and an antiinflammatory agent. Dapsone alone or in combination with other drugs has been used for the prevention and treatment of infectious diseases (e.g., leprosy, malaria, and actinomycetoma, as well as
Pneumocystis jirovecii
pneumonia in persons with human immunodeficiency virus HIV infection) and chronic inflammatory diseases characterized by the infiltration of neutrophils or eosinophils (e.g., dermatitis herpetiformis, linear IgA dermatosis, subcorneal pustular dermatosis, and erythema elevatum diutinum).
2
,
3
About 0.5 to 3.6% of persons treated with dapsone have a drug hypersensitivity syndrome,
3
–
5
which was first described by . . .
Ex vivo evaluation of personalized models can facilitate individualized treatment selection for patients, and advance the discovery of novel therapeutic options. However, for embryonal malignancies, ...representative primary cultures have been difficult to establish. We developed patient‐derived cell cultures (PDCs) from chemo‐naïve and post–treatment neuroblastoma tumors in a consistent and efficient manner, and characterized their in vitro growth dynamics, histomorphology, gene expression, and functional chemo‐response. From 34 neuroblastoma tumors, 22 engrafted in vitro to generate 31 individual PDC lines, with higher engraftment seen with metastatic tumors. PDCs displayed characteristic immunohistochemical staining patterns of PHOX2B, TH, and GD2 synthase. Concordance of MYCN amplification, 1p and 11q deletion between PDCs and patient tumors was 83.3%, 72.7%, and 80.0% respectively. PDCs displayed a predominantly mesenchymal‐type gene expression signature and showed upregulation of pro‐angiogenic factors that were similarly enriched in culture medium and paired patient serum samples. When tested with standard‐of‐care cytotoxics at human Cmax‐equivalent concentrations, MYCN‐amplified and non‐MYCN‐amplified PDCs showed a differential response to cyclophosphamide and topotecan, which mirrored the corresponding patients’ responses, and correlated with gene signatures of chemosensitivity. In this translational proof‐of‐concept study, early‐phase neuroblastoma PDCs enriched for the mesenchymal cell subpopulation recapitulated the individual molecular and phenotypic profile of patient tumors, and highlighted their potential as a platform for individualized ex vivo drug‐response testing.
We developed a system to efficiently and consistently generate patient‐derived cultures (PDCs) of neuroblastoma that recapitulated individual patient’s cytogenetic and immunohistochemical features, and phenotypic responses to standard‐of‐care chemotherapy. PDCs predominantly express the gene signature of the recently described neuroblastoma mesenchymal super‐enhancer state. This proof‐of concept provides translational evidence supporting the proposed role of the mesenchymal cell subpopulation in determining clinical treatment response and offers a novel platform for developing personalized ex vivo therapeutic decision‐making strategies for neuroblastoma.
A modified polyethersulfone (PES) membrane end-capped with magnetic-responsive iron oxides on a membrane's outermost top layer was employed to remove organic foulant from the membrane surface. The ...present work focused on the influence of pH-fluctuated aqueous mediums on the stability of the magnetite-augmented composite membrane and evaluated the relative fouling mechanism of the membrane through classical and combined membrane fouling models. Quartz crystal microbalance with dissipation (QCM-D) confirmed the stability of the membrane's magnetic-responsive functional layer throughout a feed stream pH range of 2–10. The magnetic membrane showed a loss of functionality as the magnetophoretic actuator when it was operated under an aggressive alkaline aqueous environment (pH 12). The filtration results indicate a transition of the membrane fouling mechanism, from standard pore blocking to the formation of a cake layer throughout the filtration processes. The curve that fit the results between the experimental data and the combined membrane fouling model identified cake fouling as the most critical factor that contributes to membrane fouling. Further membrane filtration tests confirmed the effectiveness of the in house-developed magnetite-augmented composite membrane to function as the magnetophoretic actuator that “prevents the organic foulants (humic acid in the present work) from approaching” and/or “detached the adsorbed foulants from” the membrane surface and greatly reduced the tendency of the cake formation for the most water-processing pH (2–10) at all times.
•The magnetophoretic-actuated PES composite membrane has better antifouling properties.•The stability of the magnetic-responsive layer in feed streams with various pH is studied.•The membrane fouling mechanism using classical and combined fouling models is studied.•Magnetophoretic actuation significantly reduced the membrane's cake fouling.
This study investigated how formative assessment is conducted in one of the secondary schools Brunei Darussalam. A framework that consisted of the five key strategies was utilised to observe two ...mathematics teachers teaching at the Year 7 and Year 10 levels. The qualitative approach was used in analysing the data in which two classroom observations and interviews with the teachers and randomly selected students were conducted. From the lesson observational findings, only a few of the characteristics from the modified key strategies were observed. The interview findings revealed contrasting findings with one teacher being aware of using formative assessment in her lesson and using activities to access her students' understandings of the lesson. However, the other teacher was not aware of using formative assessment in her lesson and prefers her students to think independently. In order to improve the teachers' performance to teach formatively, more time should be given for the teachers to plan, reflect and design formative assessment activities.
Detachment of adsorbed foulants from the membrane surface by the magnetophoretic actuation of magnetic nanoparticles. Display omitted
•Suppressed membrane fouling using magnetically responsive ...magnetite–PES membrane.•Increased interaction of Fe3O4 to the PES membrane via layer-by layer deposition.•Quantify the detachment and kinetic adsorption of foulant from membrane via QCM-D.•Induce actuation motions of Fe3O4 under an oscillating external magnetic field.•Removal of foulant (HA) through magnetophoretic actuation of the Fe3O4–PES membrane.
This study presents the surface interactions and macromolecular properties of magnetic responsive polyethersulfone (PES) membranes in relation to their potent antifouling behavior. Polyelectrolytes, polyanion poly(sodium-4-styrene-sulfonate) (PSS) and/or polycation poly(diallyldimethylammonium chloride) (PDDA), were alternately adsorbed on the surface of a PES microfiltration membrane using the polyelectrolyte multilayer modification method. Subsequently, the magnetic responsive Fe3O4 functional layer was end-capped to the polyelectrolytes-assembled-PES membrane. By using a quartz crystal microbalance with dissipation (QCM-D), the viscoelastic properties (ΔD) and adsorption kinetics (Δf) of the adsorbed adlayers were investigated. The QCM-D results demonstrated an exponential growth of Fe3O4 nanoparticles on the polyelectrolytes-assembled-PES polymer. The changes in the dissipation factor (ΔD) show greater motional freedom of the deposited multilayers (PSS, PDDA and Fe3O4) on the surface of the PES, where the surface morphology for the PES–Fe3O4 membrane was elucidated using FESEM/EDS. In this study, the synthesized magnetic responsive PES–Fe3O4 membrane demonstrated significantly improved permeability and selectivity. The membrane was shown to have a higher resistance to fouling based on the actuation motions of the magnetic nano-colloid under an oscillating external magnetic field. Subsequent exposure to a twisting effect promoted the detachment of humic acid from the membrane.
Abstract
Plastic bags are essential in human’s life on a daily basis. Most of the packaging materials used today are petroleum based manufactured polymers which are non-biodegradable. These polymers ...contribute to the landfill and take millions of years to decay. Decomposition of these plastics would also release harmful gases into the environment. On the other hand, readily available degradable plastics are expensive. Therefore, the purpose of this research is to produce a biodegradable film as a substitution for the commercial biodegradable plastics to overcome such problem. A series of biodegradable polymer films derived from polyvinyl alcohol (PVA) embedded with banana peel waste (BPW) was prepared by solution casting method. The BPW was introduced as a promoter of biodegradability of the PVA. It was found that as the amount of BPW increases, the colonies of the fungal growth on the film showed a corresponding increase, indicating higher biodegradability of the PVA composite film. The blended films with different compositions of BPW were evaluated for their tensile properties using one-factor-at-a-time (OFAT) technique and hence optimized via response surface methodology (RSM). The tensile strength of the PVA/BPW films (32.52–46.97 MPa) was found to be lower than those of unfilled PVA film (80.30 MPa). The best composition of BPW filler in this study was found to be 5.1% with respect to PVA and it is compatible to be used as a film in daily uses.
► Synthesize lateral flow membrane for potential pathogens detection in drinking water. ► Correlate membrane morphologies to its bio-sensing performances. ► Biosensor performances on protein binding ...and lateral diffusion studies.
The aim of this study was to explore the utilization of polymeric membrane for bio-sensing application in most efficient and rapid way. Customization of membrane formulation via phase separation study to modify its morphologies and properties enable the detection of different pathogens in a specific manner. Experimental findings (FESEM, through-pore distribution, porosity, capillary flow test and protein binding test) verified the predictions of faster capillary flow time and higher membrane’s protein binding by the addition of cellulose acetate and nitrocellulose to the membrane casting dope, respectively. Throughout the phase separation study, the potential phase behavior was investigated, which was correlating various membrane structures to its performances for potential pathogens detection in water.
Aims/hypothesis Evolving research suggests that common and rare alleles jointly constitute the genetic landscape of complex disease. We studied the association between 43 pathway-related candidate ...genes with 'intermediate phenotype' (i.e. corresponding plasma protein) and diabetic nephropathy in a customised microarray of 1,536 SNPs. Methods In this case-control study of type 2 diabetic Chinese individuals with and without diabetic nephropathy, cases (n = 545) were defined on the basis of a spot urinary albumin/creatinine ratio (ACR) > 113 mg/mmol; the value for controls (n = 503) was ACR < 3.3 mg/mmol. Genotyping was performed using Illumina GoldenGate assay. Results No single nucleotide polymorphism (SNP) remained significant in single locus analysis after correction for multiple testing. Therefore, we explored the best ~1% SNPs. Of these 13 SNPs, four clustered to a 5' end NADPH oxidase homologue 4 (NOX4) haplotype (GGCC frequency = 0.776) with estimated OR for diabetic nephropathy of 2.05 (95% CI 1.04-4.06) (heterozygous) and 2.48 (1.27-4.83) (homozygous) (p = 0.0055). The haplotype was correlated with plasma Cu/Zn superoxide dismutase (SOD) concentration, suggesting increased oxidative burden. Endothelin-1 SNP (rs1476046G>A, frequency = 0.252) was correlated with plasma C-terminal pro-endothelin-1 concentrations with an estimated OR for diabetic nephropathy of (heterozygous) 1.26 (0.96-1.66) and (homozygous) 1.87 (1.13-3.12) (p = 0.0072). Nitric oxide synthase 1 (NOS1) 5' haplotype (TGTC frequency = 0.38) also revealed a suggestive association with diabetic nephropathy: heterozygous 1.26 (0.95-1.67), homozygous 1.57 (1.04-2.35) (p = 0.0073). A rare NADPH oxidase homologue 1 (NOX1)-coding non-synonymous SNP (Arg315His, frequency = 0.006) was found exclusively among cases. Conclusions/interpretation Our preliminary observations suggest that common haplotypes from NOX4 and endothelin-1 SNP correlated with plasma Cu/Zn SOD and C-terminal pro-endothelin-1 concentrations, respectively, and might have conferred diabetic nephropathy susceptibility. Common NOS1 and rare NOX1 variants also revealed a suggestive association with diabetic nephropathy. Future studies to validate our observation are needed.
We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the ...top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10(-11), OR = 1.21; rs4227, P = 4.31 × 10(-10), OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10(-14), OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10(-20), OR = 1.34; rs1794275, P = 3.43 × 10(-13), OR = 1.30; rs2523946, P = 1.74 × 10(-11), OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10(-11), OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.
Objective: Heterocyclic amines (HCAs) from high-temperature cooking of meat have been linked to increased cancer incidence in Western populations, but data on the sources of HCAs in Asian diets are ...scarce. Our aim was to identify potential sources of HCAs in the Chinese diet, and to provide the basis for efforts to quantify dietary exposure to these compounds. Design and setting: We conducted 24-h dietary recall interviews among 986 Chinese men and women in Singapore, who were a randomly selected subpopulation of participants from the Singapore Chinese Health Study, a population-based cohort. Details of all foods and beverages consumed by each subject in the past 24 h were recorded, and information on meat type, cooking method and portion size were abstracted from all meat-containing dishes, and gram weight equivalents computed. Results: The mean meat intake per person was 103.0 g/day (standard deviation 74.2), of which 97.2% was fresh meat. Fish (38.0%), pork (30.6%), and poultry (21.0%) accounted for 89.6% of meat consumed. Patterns of meat consumption and cooking methods differed markedly from Western populations. Documented high-temperature cooking methods, combined with stir-frying, accounted for 44.3% of fish, 35.1% of pork and 25.6% of poultry consumed. Specifically, potentially significant sources of HCAs were pan-fried fish and barbecued pork. Conclusions: Our results identify the potential sources of HCA in the Chinese diet, highlight aspects which are relevant to HCA formation and intake, and call for novel approaches to estimating individual exposure to dietary HCAs in this and similar populations.
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