Commercial Plasma Research Articles

Streamlined turn-off fluorescence sensing of Donepezil: Enhancing evaluation in pharmaceutical formulations, quality control labs, and biological fluids at nano levels

Donepezil (DPZ) is used to treat Alzheimer’s disease by increasing acetylcholine in the brain, necessitating precise analytical methods for its evaluation. This study aims to develop and validate a new turn-off fluorescence sensing method for quantifying DPZ, enhancing its evaluation in pharmaceutical formulations, quality control laboratories, and biological fluids. By leveraging the fluorescence-quenching interplay between DPZ and tetrabromofluorescein, the assay parameters were fine-tuned to enhance the development of an ion-associated complex. The developed method demonstrated a measurement range from 40.0 to 800.0 ng/mL, with detection and quantification limits of 12.6 ng/mL and 38.0 ng/mL, respectively. However, the successful application of the method to commercial DPZ tablets and plasma samples confirmed its effectiveness for both quality control labs and clinical research settings. It ensured accurate content uniformity and high precision, making it ideal for routine DPZ monitoring. In contrast to previous methods, this approach emphasizes environmental sustainability, evaluated using advanced tools like the Eco score scale, AGREE, RGB12, and BAGI. These tools facilitated a thorough assessment of the method’s ecological impact and sustainability, underscoring its advantage over traditional methods in terms of environmental responsibility.

A-144 Liquid chromatography multiple reaction monitoring-based assay for quantitative assessment of fibrinogen levels in clinical samples

Abstract Background Fibrinogen plays a critical role in hemostasis and is essential to clot formation. Changes in the quantity or activity of fibrinogen can lead to disorders affecting coagulation. Thus, it is essential to precisely quantify fibrinogen levels to differentiate between hyperfibrinogenemia in hypercoagulable disorders and dysfibrinogenemia, hypo/afibrinogenemia, and irregular bleeding. Current diagnostic tests that use antibodies to detect fibrinogen or activity-based measures are susceptible to interference from heparin contamination, hemolysis, and hyperbilirubinemia. Here, we evaluated the use of targeted proteomics for developing a quantitative assay for fibrinogen in plasma samples. Methods Four peptides each for alpha and gamma chains of fibrinogen were synthesized using FMOC chemistry on a Liberty Blue (CEM Corp) peptide synthesizer. A targeted multiple reaction monitoring (MRM) assay was developed and optimized using Dionex Ultimate 3000 HPLC connected to a TSQ Altis triple quadrupole mass spectrometer (Thermo Scientific). Evaluations were conducted using a range of standards, such as pure protein, WHO plasma and commercially available plasma with known fibrinogen amounts for the accurate quantitation of fibrinogen. Calibration curves were generated using different dilutions in various matrices. The repeatability and precision of the assay were evaluated across five different days. The plasma samples were processed and digested in a 96-well plate and subjected to C18 clean-up using a Bravo automated liquid handler (Agilent). All samples were spiked-in with corresponding heavy-labeled peptides prior to digestion with trypsin. Multiple reaction monitoring assays were performed on tryptic digests of plasma samples. Results Calibration curves using commercial plasma for all peptides showed linearity from 20 mg/dl to 1,308 mg/dl. This covers the entire clinical range including normal (200-350 mg/dl), deficient states (<100 mg/dl) and excess production (>350 mg/dl) that can be used for evaluation of bleeding disorders including consumption coagulopathy and hyperfibrinogenemia. Based on the overall performance in terms of linearity, limit of detection/quantitation, carryover and coefficient of variation (CV) across five different days, two peptides per chain were finally selected for developing the quantitative assay. The intra-assay variability was <5% and intra-day CV was ∼20%. This assay is currently being tested on a variety of clinical samples representing a range of fibrinogen levels. Conclusions Our study focused on assessing whether multiplexed MRM assay could be implemented to measure fibrinogen levels in plasma. Our data indicate the feasibility of MRM-based assays for determining fibrinogen levels as an alternative to existing non-mass spectrometry-based activity or antigen assays.

Thrombin generation to evaluate the complex hemostatic balance of hemophilia A plasma containing direct oral anticoagulant and supplemented by factor VIII

BackgroundThe incidence of cardiovascular diseases is increasing in persons with hemophilia A (HA). Therefore, anticoagulant therapy based on direct oral anticoagulants (DOACs) may be needed, despite the bleeding risk. In case of surgery or bleeding, such patients may be concomitantly treated with emicizumab (routine prophylaxis), factor (F)VIII products, and DOAC. Their concomitant presence constitutes a hemostatic challenge. Recent international guidelines stated that data are scarce on the hemostatic balance of plasma samples from patients with HA receiving emicizumab and DOAC. ObjectivesThe aim of this observational study was to assess the coagulation of FVIII-deficient plasma spiked with DOAC and emicizumab and to evaluate the effects of FVIII addition. MethodsProthrombin time, activated partial thromboplastin time, and thrombin generation (TG) using the calibrated automated thrombogram method were evaluated in aliquots of a commercial severe HA plasma supplemented with emicizumab (0, 12.5, 25, 50, and 100 ng/mL), DOAC (0, 50, 100, 200, and 400 ng/mL of apixaban, rivaroxaban, edoxaban, or dabigatran) and FVIII (0%, 5%, 15%, 50%, and 100%). ResultsDOAC rapidly induced a TG decrease. Emicizumab could counter this effect only for the lowest DOAC dose. FVIII addition to the FVIII-deficient plasma containing a DOAC and emicizumab improved TG and countered the anticoagulant effect of DOAC at ≤100 ng/mL. ConclusionOur findings indicate that FVIII can be safely used with emicizumab to counter the anticoagulant effect of DOAC at ≤100 ng/mL. The TG assay is an efficient tool to monitor plasma containing anti-FXa DOAC, but not dabigatran (anti-FIIa).

Physical and chemical diagnostics of cold atmospheric pressure argon plasma jet

AbstractThis article presents an experimental investigation of an argon plasma jet. It examines a commercial argon plasma jet device's physical, chemical, and biological impacts, comparing findings against global standards. The study focuses on electrical features ensuring safety for patients and consumers, finding all leakage current values within established standards. Chemical analysis of emitted gases shows no detectable levels of harmful compounds near treated skin. Optical emission spectroscopy reveals bioactive compounds within the plasma jet. UV radiation emission remains within safety thresholds. Hyperspectral imaging shows temporary increases in skin characteristics posttreatment, reverting to baseline over time. Overall, the study demonstrates the safety and potential of the argon plasma jet in skin treatment.

Stagnant liquid layer as “Microreaction System” in submerged plasma Micro-Jet for formation of carbon quantum dots

This study aims to intensify reactivity via bespoke transient hydrodynamics in a plasma-activated three-phase catalyst system. Likewise, three-phase plasma systems in literature are not well designed, understood and commercially available. The synthesised N-doped carbon quantum dots, with application as fertilisers and wastewater treatment was evaluated as a model reaction. A plasma microjet was produced using a commercial plasma system, creating an almost flat, large interface covering a thin stagnant liquid layer with a catalyst bed underneath. In this hydrodynamic regime, plasma can penetrate the catalyst bed via the stagnant thin liquid film and polarise the plasma-liquid interface. The new process regime’s effectiveness is proven by the enhanced reaction rate achieved by raising liquid diffusivity toward the catalyst bed through solvent viscosity reduction. Results indicate that the reaction rate depends on the small surface area interacted with the plasma jet amid an excess of excited species, not the total gas–liquid interface area. The plasma process competes energetically with the best dielectric barrier discharge processes and uses less energy than microfluidic processing in chemical microreactors. High momentum transfer from the plasma jet to the liquid partly evaporates non-water additives, impacting process design and requiring reduction.

Rapid oxidation of semiconductors at room temperature with a basic plasma cleaner

This paper shows how a simple modification of the electrodes in a basic commercial plasma cleaner allowed the oxidation of compound semiconductors (GaAs) and Si at room temperature. We explained the oxidation of the semiconductor surface by the participation of aluminum atoms evaporated from the electrode surface in the discharge, which resulting in additional ultraviolet (UV) radiation from the plasma. The UV radiation not only increases the decomposition of oxygen molecules adsorbed on the surface but also results in photoionization of GaAs with the formation of Ga and As ions at the oxide–GaAs interface. In addition to obtaining oxides on semiconductor surfaces, the modified device proved to be an effective tool for etching amorphous carbon films.

Effect of Non-Meat Proteins on Storage Characteristics and Amino Acid Composition of Pork Emulsified Sausages.

This study was conducted to confirm the following effects of non-meat binders (NMB) on proximate composition, pH, cooking yield, amino acids, volatile basic nitrogen (VBN), thiobarbituric acid reactive substance (TBARS), and correlation of pork emulsified sausages during refrigerated storage. The following groups of sausage samples were manufactured: Control (non-addition), BBP (1% bovine blood plasma); PBP (1% porcine blood plasma), EWP (1% white egg powder), CPPP (1% commercial porcine plasma powder), ISP (1% isolated soy protein), SP (1% seaweed powder), and SC (1% sodium caseinate). When NMB was added, ISP, SP, and SC showed higher heating yields while PBP showed lower heating yields than the control. As a result of amino acid analysis, PBP, CPPP, and SC showed significantly higher serine content than the control. EWP and SC showed significantly lower TBARS values than the control group, and VBN did not exceed 20 mg% in any treatments until the 5th week. These results demonstrate that SC is a NMB that can lower TBARS value while improving heating yield and serine content.

Integrated approach of white analytical chemistry and design of experiments to microwave-assisted sensitive and eco-friendly spectrofluorimetric estimation of mirabegron using 4-chloro-7-nitrobezofuran as biosensing fluorescent probe

The USFDA recently approved mirabegron, a novel once-daily β-3 adrenoceptor agonist for oral administration, as a transformative treatment for overactive bladder. Despite the existence of numerous analytical methods for the assay and bioanalysis of mirabegron, it’s perplexing that none have explored the domain of microwave-assisted sensitive spectrofluorimetric method for mirabegron estimation, even after extensive literature review. Adding to the enigma is the insistence of current analytical methods on using expensive and harmful organic solvents, posing a threat to marine life and the broader environment. Recently, the white analytical chemistry approach has been introduced to develop analytical methods that are cost-effective, environmentally friendly, and user-friendly. Consequently, a white analytical chemistry-based, sensitive, and eco-friendly spectrofluorimetric estimation of mirabegron has been initiated, using 4-Chloro-7-nitrobenzofurazan as a fluorescent biosensing probe. The development of this robust method involved a series of experiments designed to minimize solvent and time wastage. Through a combination of fractional factorial and Box-Behnken designs, researchers identified the critical variables and optimized the method to perfection. This method was validated according to the stringent ICH Q2 (R2) and USFDA guidelines, ensuring its reliability and accuracy. Once approved, this sensitive spectrofluorimetric method was tested, accurately estimating mirabegron levels in commercial formulations and rat plasma samples. To further enrich the study, a comprehensive evaluation of existing analytical methods was conducted alongside the proposed spectrofluorimetric method, using advanced tools like the AGREE calculator, GAPI software, and RGB model to assess their eco-friendliness and effectiveness in mirabegron estimation.

An economy of immunity: The racial‐spatial lives of antibodies in the American blood plasma economy from 1960s prisons to COVID‐19

AbstractIn 2020, a market in convalescent blood plasma developed as a potential treatment for COVID‐19. During this time, commercial plasma centres—which collect the blood plasma from paid donors for pharmaceutical production—paid recovered patients as much as US$100 for a donation of blood plasma containing COVID‐19 antibodies, from which they manufactured an experimental treatment. This paper uses the commercial collection of COVID‐19 antibodies found in plasma as an entry point into exploring how racially uneven exposures to disease may produce biovalue. The first section considers the spatial history of antibody‐derived plasma products, using historical research to examine how inmates at predominantly black plantation‐prisons in the US South were valued for antibody production in the 1960s. Against this historical relief, the second section examines the spatiality of antibodies in current practices of the plasma industry, as well as in the plasma industry's response to the COVID‐19 pandemic (even as those efforts eventually failed in clinical trials). If geographical literatures on environmental exposure, as well as on COVID‐19 transmission, discuss exposure as an outcome of racial capitalism, this paper emphasises the productive opportunities that capital can solicit from exposures, especially those that are useful to different forms of biomedicine. By critically scrutinising the practice of ‘sharing immunity’ and attending to its decidedly geographic constitution, we can see how what Ruth Wilson Gilmore calls the ‘death‐dealing logics’ of racial capitalism may also work through the seemingly affirmative practices and communal imaginaries behind the redistribution of antibodies as medicine.

Measurement of recombinant porcine factor VIII in patients with congenital haemophilia A and inhibitors in the presence of emicizumab.

Recombinant porcine factor VIII (rpFVIII) is a treatment option for break-through bleeds in patients with congenital haemophilia A with inhibitors (CHAwI) on emicizumab. However, there are limited data about the measurement of rpFVIII in the presence of emicizumab. To analyse whether rpFVIII can be measured with a chromogenic assay with bovine component (bCSA) in plasma from CHAwI on emicizumab treatment. In the first part of the study, FVIII deficient plasma was spiked with rpFVIII, in the second part, commercial plasma from CHAwI was spiked with emicizumab and rpFVIII, and in the third part, plasma from CHAwI on emicizumab treatment was spiked with rpFVIII. FVIII was then measured with bCSA and a chromogenic assay with human component (hCSA). Thrombin generation (TG) and clot-waveform analysis (CWA) were also carried out. The recovery of rpFVIII measured with bCSA is approximately 80% and is further influenced by the presence of an anti-porcine inhibitor. rpFVIII assessed with hCSA was influenced by emicizumab. CWA and TG showed a weak correlation with baseline emicizumab concentration, but peak thrombin and CWA correlated well with increasing emicizumab concentrations and rpFVIII activities. This study indicates that rpFVIII can be measured in the presence of emicizumab with a bCSA. A calibration curve for the measurement of rpFVIII with bCSA should be established.

Behavioral verification and risk factors of HIV cross-population transmission in China: analysis of national surveillance data 1989–2022

IntroductionThe dynamic HIV/AIDS epidemic significantly impacts China, particularly affecting injection drug users (IDUs), former plasma donors (FPDs), men who have sex with men (MSM), and those engaging in high-risk heterosexual behavior (HRHB). This study specifically focuses on identifying the risk factors and influences that drive the spread of HIV among these population groups by performing a comprehensive analysis of contact histories of individuals diagnosed with HIV.MethodsData for this research were gathered from China’s HIV/AIDS Comprehensive Response Information Management System (CRIMS). Contact histories were described using bar and venn diagram. Trend in engaging in HBRB among MSM were identify potential change using the Cochran-Armitage test. Logistic regression was employed to analyze the factors influencing HBRB in MSM.ResultsFrom 1989 through to 2022, a total of 1,457,218 individuals aged 15 years or older in China, who reported being infected with HIV, indicated they had one or more types of contact histories including injecting drug use, male homosexual behavior, commercial plasma donation, and high-risk heterosexual behavior. Among these, 97.0% reported a single type of contact history, while 3.0% reported having multiple contact histories. Of those with multiple contact histories, 98.0% (42,258 individuals) had engaged in HRHB. Among all HIV-infected IDUs, MSM, and FPDs, their respective proportions of engagement in HRHB were 11.8%, 5.7% and 6.2%. Prior to 2012, most were reported to be IDUs; however, subsequent to this, most reported being MSM. Factors that heightened the risk of engaging in HRHB among HIV-infected MSM included being of age between 25–34 years [adjusted odds ratio (AOR) = 1.29] or 35–44 years (AOR = 1.22), marital status such as being married (AOR = 1.23) or being divorced/widowed (AOR = 1.17), belonging to an ethnic minority (AOR = 1.29), receiving diagnosis in hospitals (AOR = 1.81), residing in rural areas (AOR = 1.12), among others. However, the risk of HRHB decreased when age ≥ 55 years (55–64 years: AOR = 0.82; ≥ 65 years: AOR = 0.64).ConclusionThe potential for HIV transmission among diverse populations is substantial. As such, it is imperative that strategies are implemented to mitigate the propagation of HIV to the general populace via heterosexual intercourse.

Plasma Cleaning of Hydrocarbon and Carbon Contaminated Surfaces of Accelerator Components

To achieve the vacuum quality required for the operation of particle accelerators, the surface of the vacuum vessels must be clean from hydrocarbons. This is usually achieved by wet chemistry processes, e.g., degreasing chemical baths that, in case of radioactive vessels, must be disposed accordingly. An alternative way exploits the oxygen plasma produced by a downstream RF plasma source. This technique offers the possibility of operating in-situ, which is an advantageous option to avoid the handling of voluminous and/or fragile components and a more sustainable alternative to large volume disposable baths. In this work, we test a commercial plasma source in dedicated vacuum systems equipped with quartz crystal microbalances (QCMs). The evolution of the etching rates of amorphous carbon (a-C) thin films deposited on the QCMs to mimic contamination are studied as function of operating parameters. We present the results of the plasma cleaning process applied to the real case of a hydrocarbons-contaminated large vacuum vessel. The studies are complemented by transport simulations and surface contamination monitoring by X-ray photoelectron spectroscopy (XPS) analysis. The evaluation of the vessel cleanliness, which is performed via residual gas analysis (RGA) measurements, is based on CERN’s outgassing acceptance criteria and agrees with both simulations and XPS results.

Ion concentration ratio measurements of ion beams generated by a commercial microwave electron cyclotron resonance plasma source.

A commercially available electron cyclotron resonance (ECR) plasma source (GenII Plasma Source, tectra GmbH) is widely used for surface processing. This plasma source is compatible with ultrahigh vacuum systems, and its working pressure is relatively low, around 10-6-10-4 Torr even without differential pumping. Here, we report ion flux concentration ratios for each ion species in an ion beam from this source, as measured by a mass/energy analyzer that is a combination of a quadrupole mass spectrometer, an electrostatic energy analyzer, and focusing ion optics. The examined beams were those arising from plasmas produced from feed gases of H2, D2, N2, O2, Ar, and dry air over a range of input power and working pressures. H2(D2) plasmas are widely used for nuclear fusion applications and, hence, the ion concentration ratios of H+, H2+, and H3+ reported here will be useful information for research that applies this plasma source to well-controlled plasma-material interaction studies. Ion energy distributions, stability of operation, and impurity concentrations were also assessed for each of the plasma species investigated.

A global comparative field study to evaluate the factor VIII activity of efanesoctocog alfa by one-stage clotting and chromogenic substrate assays at clinical haemostasis laboratories.

Structural and chemical modifications of factor VIII (FVIII) products may influence their behaviour in FVIII activity assays. Hence, it is important to assess the performance of FVIII products in these assays. Efanesoctocog alfa is a new class of FVIII replacement therapy designed to provide both high sustained factor activity levels and prolonged plasma half-life. Evaluate the accuracy of measuring efanesoctocog alfa FVIII activity in one-stage clotting assays (OSAs) and chromogenic substrate assays (CSAs). Human plasma with no detectable FVIII activity was spiked with efanesoctocog alfa or a full-length recombinant FVIII product comparator, octocog alfa, at nominal concentrations of 0.80 IU/mL, 0.20 IU/mL, or 0.05 IU/mL, based on labelled potency. Clinical haemostasis laboratories (N=35) tested blinded samples using in-house assays. Data from 51 OSAs (14 activated partial thromboplastin time [aPTT] reagents) and 42 CSAs (eight kits) were analyzed. Efanesoctocog alfa activity was reliably (±25% of nominal activity) measured across all concentrations using OSAs with Actin FSL and multiple other aPTT reagents. Under- and overestimation of FVIII activity occurred with some reagents. No specific trend was observed for any class of aPTT activators. A two- to three-fold overestimation was consistently observed using CSAs and the OSA with Actin FS as the aPTT reagent across evaluated concentrations. Under- or overestimation occurred with some specific OSAs and most CSAs, which has been previously observed with other modified FVIII replacement products. Efanesoctocog alfa FVIII activity was measured with acceptable accuracy and reliability using several OSA methods and commercial plasma standards.

Development and Comparative Evaluation of Two Different Label-Free and Sensitive Fluorescence Platforms for Analysis of Olaparib: A Recently FDA-Approved Drug for the Treatment of Ovarian and Breast Cancer.

Olaparib (OLA) is a PARP inhibitor drug which has been recently approved by the Food and Drug Administration (FDA) for the treatment of ovarian and breast cancer. A convenient analytical tool for the quantitation of OLA in its dosage form and plasma samples was urgently needed. This study describes, for the first time, the development of two different label-free and sensitive fluorescence-based platforms for the pharmaceutical and bioanalysis of OLA. These platforms were microwell-assisted with a fluorescence microplate reader (MW-FLR) and high-performance liquid chromatography with fluorescence detection (HPLC-FD). Both MW-FLR and HPLC-FD employed the native fluorescence of OLA as an analytical signal. The MW-FLR involved measuring the fluorescence signals in 96-well white-opaque plates. The HPLC-FD involved chromatographic separation of OLA and duvelisib (DUV), as an internal standard on a Nucleosil-CN HPLC column (250 mm length × 4.6 mm i.d., 5 µm particle diameter) with a mobile phase composed of acetonitrile: water (25:75, v/v) pumped at a flow rate of 1.7 mL/min. Elution of OLA and DUV was detected using a fluorescence detector. The optimal conditions of both MW-FLR and HPLC-FD were established, and they were validated according to the guidelines of the International Council for Harmonization for the validation of analytical procedures. The linear ranges of MW-FLR and HPLC-FD were 25-1000 and 5-200 ng/mL, respectively, with limits of detection of 15 and 1.7 ng/mL, respectively. The accuracy and precision of both platforms were confirmed as the recovery values were ≥98.2% and the relative standard deviations (RSD) were ≤2.89%. Both methodologies were satisfactorily applied to the quantitation of OLA in its commercial dosage form (Lynparza® tablets) and plasma samples with high accuracy and precision. The greenness of both MW-FLR and HPLC-FD was assessed using two different multiple parameter-based metric tools, and the results proved their greenness and adherence to the requirements of green analytical approaches. Both platforms have simple procedures and acceptable levels of analytical throughput. In conclusion, the proposed MW-FLR and HPLC-FD are valuable tools for routine use in quality control and clinical laboratories for the quantitation of OLA for the purposes of pharmaceutical quality control, pharmacokinetic studies, and bioequivalence testing.

Innovative micellar-UPLC approach for concomitant determination of favipiravir and remdesivir with four co-administered cardiovascular drugs in their pharmaceuticals and spiked plasma: Greenness and whiteness assessment

Many COVID-19 patients have pre-existing cardiovascular diseases, which are strongly linked to the high incidence of severe COVID-19. The experts advised such patients to prioritize drug treatments as per the physician's recommendations to avoid aggravation of the basic diseases. Hence, the development of an analytical approach for the concurrent determination of drugs prescribed for the co-treatment of COVID-19 and cardiovascular diseases acquires significant importance in QC units and bioavailability centers. Herein, a micellar-UPLC approach was first devised for the concomitant analysis of aspirin, atenolol, atorvastatin, losartan, favipiravir, and remdesivir as co-administered drugs, either with or without salicylic acid. On ACQUITY UPLC C18 column, the aforesaid drugs were isocratically separated employing a micellar eluent system. This system consisted of 0.03 M Brij-35, 0.15 M sodium dodecyl sulfate, and 0.02 M sodium dihydrogen phosphate (pH 5.0) as the mobile phase A (90%) and n-propanol as the mobile phase B (10%). The eluent system was pumped at a flow rate of 0.50 mL.min−1 for 5.50 min, which was suddenly increased to 0.80 mL.min−1 for 2.50 min. The separated peaks were scanned at 240 nm. The suggested approach was validated following ICH requirements for linearity, robustness, accuracy, specificity, precision, and detection and quantitation limits. The suggested approach was applied successfully to commercial products and human plasma without any intrusion from excipients or plasma matrices. The suggested approach’s greenness was appraised employing five metrics namely: eco-scale, GAPI, NEMI, Raynie and Driver, and AGREE. Furthermore, the suggested approach’s whiteness features were investigated using the recently unveiled RGB12 model. The suggested approach outperformed the reported approaches in terms of greenness and whiteness. The sensitivity, high sample throughput, and short runtime (7.40 min) of the suggested approach assert its aptness for routine determination of the aforesaid drugs.

Exploring the increasing need for plasma collection: Perspectives of voluntary nonremunerated donors on payment for plasma in Canada.

The aim of this paper is to understand how voluntary nonremunerated plasma donors in Canada view payment for plasma and the emerging commercial sector. There is a growing global demand for plasma, to produce plasma-derived medical products. Source plasma for these products is collected through voluntary nonremunerated donation, sometimes by a national blood service, or by a commercial plasma collector, remunerating donors. This paper presents findings from qualitative semi-structured interviews with source plasma donors in three new source plasma centres in Canada. Interview data were analysed using abductive analysis, an interpretivist approach that builds on grounded theory. This study indicates that there are a range of perspectives on payment for plasma and the emerging commercial sector, from disinterest in payment, to opposition to payment based on the belief that it could undermine donating to help others, and risk public health and safety. One fifth of participants are open to CBS paying donors if it is necessary to increase national sufficiency of plasma. Almost two thirds of participants are opposed to commercial plasma collection in Canada, claiming that it could undermine Canada's public healthcare system, raising questions about transparency and accountability of the commercial plasma industry. Findings point to important areas for future study, on publicly collected source plasma, the emerging commercial plasma sector, and the role of the donor as a social actor in a complex political system.

Denoising Autoencoder Normalization for Large-Scale Untargeted Metabolomics by Gas Chromatography-Mass Spectrometry.

Large-scale metabolomics assays are widely used in epidemiology for biomarker discovery and risk assessments. However, systematic errors introduced by instrumental signal drifting pose a big challenge in large-scale assays, especially for derivatization-based gas chromatography-mass spectrometry (GC-MS). Here, we compare the results of different normalization methods for a study with more than 4000 human plasma samples involved in a type 2 diabetes cohort study, in addition to 413 pooled quality control (QC) samples, 413 commercial pooled plasma samples, and a set of 25 stable isotope-labeled internal standards used for every sample. Data acquisition was conducted across 1.2 years, including seven column changes. In total, 413 pooled QC (training) and 413 BioIVT samples (validation) were used for normalization comparisons. Surprisingly, neither internal standards nor sum-based normalizations yielded median precision of less than 30% across all 563 metabolite annotations. While the machine-learning-based SERRF algorithm gave 19% median precision based on the pooled quality control samples, external cross-validation with BioIVT plasma pools yielded a median 34% relative standard deviation (RSD). We developed a new method: systematic error reduction by denoising autoencoder (SERDA). SERDA lowered the median standard deviations of the training QC samples down to 16% RSD, yielding an overall error of 19% RSD when applied to the independent BioIVT validation QC samples. This is the largest study on GC-MS metabolomics ever reported, demonstrating that technical errors can be normalized and handled effectively for this assay. SERDA was further validated on two additional large-scale GC-MS-based human plasma metabolomics studies, confirming the superior performance of SERDA over SERRF or sum normalizations.

Investigation of bovine serum albumin‐specific IgE expression in horses

SummaryBackgroundNeonatal foals are born essentially agammaglobulinaemic and therefore must ingest colostrum or receive immunoglobulins to maintain health. Failure of passive transfer treatment involves administration of equine colostrum, plasma or commercial powdered colostrum (CPC). Anecdotal reports suggest the risk of anaphylaxis associated with plasma transfusion in neonates receiving CPC prior to gut closure. Bovine serum albumin (BSA) in CPC may serve as a target for BSA‐specific immunoglobulin E (IgE) in donor equine plasma.ObjectivesTo determine the presence of BSA‐specific IgE in samples of commercial equine plasma, samples were collected following routine vaccination in healthy horses and horses experiencing adverse vaccine reactions.Study designProspective observational.MethodsSerum was collected from: 65 healthy horses at days 0, 14, 28, 90, 180, 270 and 365 post‐vaccination; 26 horses after vaccine reaction at days 1, 180 or 270 post‐vaccination; 4 horses not vaccinated; and 9 horses from a commercial plasma donor herd. BSA‐specific IgE was determined using enzyme‐linked immunosorbent assay.ResultsBovine serum albumin‐specific IgE was not detected in non‐vaccinated horses and was identified in all vaccinated horses. Younger horses demonstrated a trend for higher fold changes in post‐vaccination BSA‐specific IgE expression compared to older horses. No significant difference in BSA‐specific IgE levels between commercial plasma donors and healthy horses was identified. No significant difference in post‐vaccination BSA‐specific IgE levels between the reactor and healthy horses at days 180 and 270 post‐vaccination were identified.Main limitationsSmall number of reactor horses at day 180 and 270 post‐vaccination with most samples being collected 24 h. There were no healthy horse samples for 24 h post‐vaccination; therefore, it was not possible to compare the groups at this timepoint.ConclusionsHorses may express BSA‐specific IgE following vaccination. There may be a risk of hypersensitivity type reaction when veterinarians administer commercial plasma to neonatal foals consuming CPC prior to gut closure.

Exploiting synergistic effects: Cheap ultra-sensitive electrochemical rutin detection using WO3/rGO nanocomposite in combination with multiwalled carbon nanotubes

Multiwalled carbon nanotubes (MWCNTs) are extensively studied due to their enhanced signal response, improved stability, selectivity, and versatility in fabrication, especially combined with designed materials; however, costly and time-consuming preparation are obstacles to their implementation in routine analyses. Therefore, we propose a tungsten oxide (WO3) and reduced graphene oxide (rGO) nanocomposite (WO3-G/MWCNT) that was mixed with MWCNTs and presented interesting results. We prepared the nanocomposite using a fast and facile route using in situ generated atomic hydrogen species; also, it was easily characterized by Scanning Electron Microscopy, Raman, and X-ray Spectroscopy. The nanocomposite was deposited on a glassy carbon electrode (GCE) and investigated as a voltammetric sensor for ultra-sensitive rutin quantification; a synergic effect towards rutin oxidation was observed by a 30-fold current increase in comparison to the bare GCE. Under optimized conditions, square wave voltammetry was performed, presenting a linear range from 0.183 to 2.849 µmol/L. The limits of detection and quantification were 9.00 and 65.00 nmol/L, respectively. High selectivity was noticed in quantifying 1.75 µmol/L rutin in the presence of ascorbic acid, citric acid, caffeine, glucose, and naringenin, which was attributed to the high signal response and sensitivity of WO3-G/MWCNT/GCE. High accuracy was also noticed for determining rutin in synthetic human serum and commercial plasma samples, with a recovery range of 85.5–108.7%. Those results confirm that the easy fabrication of WO3-G/MWCNT can be an excellent alternative for manufacturing ultra-sensitive sensors with promising features to be explored for drug monitoring and quality control of pharmaceuticals.