scholarly journals Multiplexed micronutrient, inflammation, and malarial antigenemia assessment using a plasma fractionation device

2021 ◽  
Author(s):  
Eleanor Brindle ◽  
Lorriane L. Lillis ◽  
Rebecca Barney ◽  
Pooja Bansil ◽  
Francisco Arredondo ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Whole Blood ◽  
Large Scale ◽  
Disease Status ◽  
Dried Blood Spots ◽  
Micronutrient Deficiencies ◽  
Protein Biomarkers ◽  
Micronutrient Status ◽  
Highly Correlated ◽  
Finger Stick

Collecting, processing, and storing blood samples for future analysis of biomarkers can be challenging when performed in resource limited environments. The preparation of dried blood spots (DBS) from heel or finger stick collection of whole blood is a widely used and established method. DBS pose less risk of infection from blood borne pathogens, do not require immediate specimen processing and tolerate a wider range of storage temperatures, and are easier to ship. As such, DBS are commonly used in large-scale surveys to assess infectious disease status and/or micronutrient status in vulnerable populations. Recently, we reported that DBS can be used with a multiplexed immunoassay, the Q-plex Human Micronutrient 7-plex Array (MN 7-plex). This tool can simultaneously quantify seven protein biomarkers related to micronutrient deficiencies (iodine, iron and vitamin A), inflammation and malarial antigenemia using plasma or serum. Serum ferritin, a key iron biomarker, cannot be measured from DBS due to red blood cell (RBC) ferritin confounding the results. In this study, we demonstrate the performance of a simple and rapid blood fractionation tool that passively separates serum from cellular components via diffusion through a membrane into a plasma collection disc (PCD) to produce plasma spots. We evaluated the concordance of MN 7-plex analyte concentrations from matched panels of eighty-eight samples of PCD, DBS, and wet plasma prepared from anticoagulated venous whole blood. The results show high correlation between eluates from PCD and DBS and wet plasma for each analyte. Serum ferritin measures from the PCD eluates were highly correlated to wet plasma samples. This suggests that surveillance for iron deficiency may be improved over the current methods restricted to only measuring sTfR in DBS as when used in combination with the MN 7-plex, all seven biomarkers can be simultaneously measured using PCDs.

scholarly journals Measurement of Glycated Hemoglobin A1c from Dried Blood by Turbidimetric Immunoassay

2009 ◽  
Vol 3 (5) ◽  
pp. 1203-1206 ◽  
Author(s):  
Ramakrishnan Lakshmy ◽  
Ruby Gupta
Keyword(s):  
Whole Blood ◽  
Large Scale ◽  
Hemoglobin A1c ◽  
Glycated Hemoglobin ◽  
Intraclass Correlation ◽  
Dried Blood Spots ◽  
Sample Collection ◽  
Blood Spots ◽  
Glycated Hemoglobin A1c ◽  
The Impact

Background: Glycated hemoglobin A1c (A1C) is an important marker in the diagnosis and treatment of diabetes. Dried blood measurement of A1C is useful in large scale epidemiological evaluation of A1C, especially to assess the impact of intervention programs. The possibility of using dried blood for measurement of A1C by the immunoturbidimetric method was explored in the present study. Method: Blood was collected from 30 patients, and blood spots were prepared and dried. The dried blood spot samples were kept for different lengths of time at 4°C to assess stability. Glycated hemoglobin was measured in whole blood and dried blood on the day of collection as well as on days 10 and 15 by immunoturbidimetric method. Results: The A1C values of 30 samples analyzed for comparison between whole blood estimation and dried blood ranged from 4.6% to 9.9%. The mean A1C on the day of sample collection was 6.01% ± 1.58% in fresh whole blood samples and 5.94% ± 1.58 % in dried blood spots. A linear and highly correlated relationship was observed between dried blood A1C values and those in whole blood ( r = 0.986 and intraclass correlation value = 0.993). Glycated hemoglobin values on day 10 and day 15 were comparable with the values on day 1 with a shift in mean of just 1% on day 10 and 3.04% on day 15. Conclusion: In conclusion, dried blood can be used for measurement of A1C by immunoturbidimetric method, and further stability of A1C measurement from dried blood for up to 15 days at 4°C makes it an ideal matrix for transportation in developing countries like India.

scholarly journals A critical evaluation of results from genome-wide association studies of micronutrient status and their utility in the practice of precision nutrition

2019 ◽  
Vol 122 (2) ◽  
pp. 121-130 ◽  
Author(s):  
Marie-Joe Dib ◽  
Ruan Elliott ◽  
Kourosh R. Ahmadi
Keyword(s):  
Large Scale ◽  
Association Studies ◽  
Critical Evaluation ◽  
Water Soluble ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Micronutrient Deficiencies ◽  
Micronutrient Status ◽  
Genome Wide ◽  
Fat Soluble Vitamins

AbstractRapid advances in ‘omics’ technologies have paved the way forward to an era where more ‘precise’ approaches – ‘precision’ nutrition – which leverage data on genetic variability alongside the traditional indices, have been put forth as the state-of-the-art solution to redress the effects of malnutrition across the life course. We purport that this inference is premature and that it is imperative to first review and critique the existing evidence from large-scale epidemiological findings. We set out to provide a critical evaluation of findings from genome-wide association studies (GWAS) in the roadmap to precision nutrition, focusing on GWAS of micronutrient disposition. We found that a large number of loci associated with biomarkers of micronutrient status have been identified. Mean estimates of heritability of micronutrient status ranged between 20 and 35 % for minerals, 56–59 % for water-soluble and 30–70 % for fat-soluble vitamins. With some exceptions, the majority of the identified genetic variants explained little of the overall variance in status for each micronutrient, ranging between 1·3 and 8 % (minerals), <0·1–12 % (water-soluble) and 1·7–2·3 % for (fat-soluble) vitamins. However, GWAS have provided some novel insight into mechanisms that underpin variability in micronutrient status. Our findings highlight obvious gaps that need to be addressed if the full scope of precision nutrition is ever to be realised, including research aimed at (i) dissecting the genetic basis of micronutrient deficiencies or ‘response’ to intake/supplementation (ii) identifying trans-ethnic and ethnic-specific effects (iii) identifying gene–nutrient interactions for the purpose of unravelling molecular ‘behaviour’ in a range of environmental contexts.

scholarly journals Quantification of Rifapentine, a Potent Antituberculosis Drug, from Dried Blood Spot Samples Using Liquid Chromatographic-Tandem Mass Spectrometric Analysis

2014 ◽  
Vol 58 (11) ◽  
pp. 6747-6757 ◽  
Author(s):  
Teresa L. Parsons ◽  
Mark A. Marzinke ◽  
Thuy Hoang ◽  
Erin Bliven-Sizemore ◽  
Marc Weiner ◽  
...  
Keyword(s):  
Whole Blood ◽  
Dried Blood Spots ◽  
Population Based ◽  
Spectrometric Analysis ◽  
Tandem Mass ◽  
Antituberculosis Drug ◽  
Dose Escalation Study ◽  
Drug Concentrations ◽  
Tandem Mass Spectrometric ◽  
Finger Stick

ABSTRACTThe quantification of antituberculosis drug concentrations in multinational trials currently requires the collection of modest blood volumes, centrifugation, aliquoting of plasma, freezing, and keeping samples frozen during shipping. We prospectively enrolled healthy individuals into the Tuberculosis Trials Consortium Study 29B, a phase I dose escalation study of rifapentine, a rifamycin under evaluation in tuberculosis treatment trials. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying rifapentine in whole blood on dried blood spots (DBS) to facilitate pharmacokinetic/pharmacodynamic analyses in clinical trials. Paired plasma and whole-blood samples were collected by venipuncture, and whole blood was spotted on Whatman protein saver 903 cards. The methods were optimized for plasma and then validated for DBS. The analytical measuring range for quantification of rifapentine and its metabolite was 50 to 80,000 ng/ml in whole-blood DBS. The analyte was stable on the cards for 11 weeks with a desiccant at room temperature and protected from light. The method concordance for paired plasma and whole-blood DBS samples was determined after correcting for participant hematocrit or population-based estimates of bias from Bland-Altman plots. The application of either correction factor resulted in acceptable correlation between plasma and whole-blood DBS (Passing-Bablok regression corrected for hematocrit;y= 0.98x+ 356). Concentrations of rifapentine may be determined from whole-blood DBS collected via venipuncture after normalization in order to account for the dilutional effects of red blood cells. Additional studies are focused on the application of this methodology to capillary blood collected by finger stick. The simplicity of processing, storage, shipping, and low blood volume makes whole-blood DBS attractive for rifapentine pharmacokinetic evaluations, especially in international and pediatric trials.

scholarly journals Empiricism in Microsampling: Utilizing a Novel Lateral Flow Device and Intrinsic Normalization to Provide Accurate and Precise Clinical Analysis from a Finger Stick

2020 ◽  
Vol 66 (6) ◽  
pp. 821-831 ◽  
Author(s):  
Matthew L Crawford ◽  
Bradley B Collier ◽  
Meghan N Bradley ◽  
Patricia L Holland ◽  
Christopher M Shuford ◽  
...  
Keyword(s):  
Whole Blood ◽  
Clinical Laboratory ◽  
Sampling Technique ◽  
Dried Blood Spots ◽  
Clinical Analysis ◽  
Reference Intervals ◽  
Sample Collection ◽  
Plasma Fractions ◽  
Clinical Measurements ◽  
Finger Stick

Abstract Background Phlebotomy plays a key role in clinical laboratory medicine but poses certain challenges for the patient and the laboratory. Dried blood spots simplify collection and stabilize specimens effectively, but clinical reference intervals are based primarily on serum or plasma. We evaluated use of dried separated blood plasma specimens to simplify plasma sample collection via finger stick; however, this sampling technique posed substantial analytical challenges. We discuss herein our efforts to overcome these challenges and provide accurate and precise clinical measurements. Methods Microsamples of whole blood were collected via finger stick using a collection device employing laminar-flow separation of cellular blood and plasma fractions with subsequent desiccation. Samples were analyzed on modern autoanalyzers with FDA-approved reagent and calibration systems, as well as commercially available reagents with laboratory-developed assay parameters. Measured analyte concentrations from extracted dried plasma samples were normalized to a coextracted endogenous analyte, chloride. Results Chloride normalization reduced variability incurred through extraction and undefined plasma volume. Excellent correlation of normalized measurements from dried finger-stick samples (whole blood and plasma) versus matched venous samples facilitated developing mathematical transformations to provide concordance between specimen types. Independent end-to-end performance verification yielded mean biases &lt;3% for the 5 analytes evaluated relative to venous drawn samples analyzed on FDA-approved measurement systems. Conclusion Challenges inherent with this microsampling technique and alternate sample matrix were obviated through capabilities of modern autoanalyzers and implementation of chloride normalization. These results demonstrate that self-collected microsamples from a finger stick can give results concordant with those of venous samples.

scholarly journals Comparative performance of PCR using DNA extracted from dried blood spots and whole blood samples for malaria diagnosis: a meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aongart Mahittikorn ◽  
Frederick Ramirez Masangkay ◽  
Kwuntida Uthaisar Kotepui ◽  
Giovanni De Jesus Milanez ◽  
Manas Kotepui
Keyword(s):  
Whole Blood ◽  
Large Scale ◽  
Meta Analysis ◽  
Malaria Diagnosis ◽  
Analysis Data ◽  
Dried Blood Spots ◽  
Epidemiological Studies ◽  
Comparative Performance ◽  
Blood Spots ◽  
Significant Difference

AbstractPolymerase chain reaction (PCR) using deoxyribonucleic acid (DNA) extracted from dried blood spots (DBS) provides a fast, inexpensive, and convenient method for large-scale epidemiological studies. This study compared the performance of PCR between DNA extracted from DBS and DNA obtained from whole blood for detecting malarial parasites. Primary studies assessing the diagnostic performance of PCR using DNA extracted from DBS and whole blood for detecting malarial parasites were obtained from the ISI Web of Science, Scopus, and PubMed databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were plotted in forest plots using Review Manager version 5.3. Statistical analysis was performed via random-effects meta-analysis. Data heterogeneity was assessed using the I2 statistic. Of the 904 studies retrieved from the databases, seven were included in this study. The pooled meta-analysis demonstrated no significant difference in the comparative performance of PCR for detecting malaria parasites between DNA extracted from DBS and that extracted from whole blood (OR 0.85; 95% CI 0.62–1.16; I2 = 78%). However, subgroup analysis demonstrated that PCR using DNA extracted from DBS was less accurate in detecting Plasmodium vivax than that using DNA extracted from whole blood (OR = 0.85; 95% CI 0.77–0.94). In conclusion, a significant difference in detecting P. vivax was observed between PCR using DNA extracted from DBS and that using DNA extracted from whole blood. Therefore, P. vivax in endemic areas should be identified and detected with care with PCR using DNA obtained from DBS which potentially leads to a negative result. Further studies are required to investigate the performance of PCR using DBS for detecting P. vivax and other malarial parasites to provide data in research and routine surveillance of malaria, especially with renewed efforts towards the eradication of the disease.

scholarly journals Standardized workflow for precise mid- and high-throughput proteomics of blood biofluids

2021 ◽  
Author(s):  
Angela Mc Ardle ◽  
Aleksandra Binek, ◽  
Annie Moradian ◽  
Blandine Chazarin Orgel ◽  
Alejandro Rivas ◽  
...  
Keyword(s):  
High Throughput ◽  
Whole Blood ◽  
Large Scale ◽  
Dynamic Range ◽  
Profile Analysis ◽  
Protein Biomarkers ◽  
Throughput Analysis ◽  
Broad Dynamic Range ◽  
Plasma Fractions ◽  
Deep Profile

Background: Accurate discovery assay workflows are critical for identifying authentic circulating protein biomarkers in diverse blood matrices. Maximizing the commonalities in the proteomic workflows between different biofluids simplifies the approach and increases the likelihood for reproducibility. We developed a workflow that allows flexibility for high and mid–throughput analysis for three blood–based proteomes: naive plasma, plasma depleted of the 14 most abundant proteins, and dried blood. Methods: Optimal conditions for sample preparation and DIA–MS analysis were established in plasma then automated and adapted for depleted plasma and whole blood. The MS workflow was modified to facilitate sensitive high–throughput or deep profile analysis with mid–throughput analysis. Analytical performance was evaluated from 5 complete workflows repeated over 3 days as well as a linearity analysis of a 5—6–point dilution curve. Result: Using our high-throughput workflow, 74%, 93%, 87% of peptides displayed an inter-day CV<30% in plasma, depleted plasma and whole blood. While the mid-throughput workflow had 67%, 90%, 78% of peptides in plasma, depleted plasma and whole blood meeting the CV<30% standard. Lower limits of detection and quantitation were determined for proteins and peptides observed in each biofluid and workflow. Combining the analysis of both high–throughput plasma fractions exceeded the number of reliably identified proteins for individual biofluids in the mid–throughput workflows. Conclusion: The workflow established here allowed for reliable detection of proteins covering a broad dynamic range. We envisage that implementation of this standard workflow on a large scale will facilitate the translation of candidate markers into clinical use.

Comparison of Cardiovascular Disease Status Between Large Scale Industry Office and Self Employed Male Workers

2011 ◽  
Vol 23 (2) ◽  
pp. 130 ◽  
Author(s):  
Keun-Ho Jang ◽  
Won-Ju Park ◽  
Myeong-Bo Kim ◽  
Dae-Kwang Lee ◽  
Hong-Jae Chae ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Large Scale ◽  
Disease Status ◽  
Male Workers

scholarly journals Scaling Up Delivery of Biofortified Staple Food Crops Globally: Paths to Nourishing Millions

2021 ◽  
pp. 037957212098250
Author(s):  
Jennifer K. Foley ◽  
Kristina D. Michaux ◽  
Bho Mudyahoto ◽  
Laira Kyazike ◽  
Binu Cherian ◽  
...  
Keyword(s):  
Pearl Millet ◽  
Large Scale ◽  
Scale Up ◽  
Lessons Learned ◽  
Raw Material ◽  
Micronutrient Deficiencies ◽  
Seed Systems ◽  
Public And Private ◽  
Context Specific ◽  
Public And Private Sector

Background: Micronutrient deficiencies affect over one quarter of the world’s population. Biofortification is an evidence-based nutrition strategy that addresses some of the most common and preventable global micronutrient gaps and can help improve the health of millions of people. Since 2013, HarvestPlus and a consortium of collaborators have made impressive progress in the enrichment of staple crops with essential micronutrients through conventional plant breeding. Objective: To review and highlight lessons learned from multiple large-scale delivery strategies used by HarvestPlus to scale up biofortification across different country and crop contexts. Results: India has strong public and private sector pearl millet breeding programs and a robust commercial seed sector. To scale-up pearl millet, HarvestPlus established partnerships with public and private seed companies, which facilitated the rapid commercialization of products and engagement of farmers in delivery activities. In Nigeria, HarvestPlus stimulated the initial acceptance and popularization of vitamin A cassava using a host of creative approaches, including “crowding in” delivery partners, innovative promotional programs, and development of intermediate raw material for industry and novel food products. In Uganda, orange sweet potato (OSP) is a traditional subsistence crop. Due to this, and the lack of formal seed systems and markets, HarvestPlus established a network of partnerships with community-based nongovernmental organizations and vine multipliers to popularize and scale-up delivery of OSP. Conclusions: Impact of biofortification ultimately depends on the development of sustainable markets for biofortified seeds and products. Results illustrate the need for context-specific, innovative solutions to promote widespread adoption.

scholarly journals EZ-ALBI Score for Predicting Hepatocellular Carcinoma Prognosis

Liver Cancer ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 734-743
Author(s):  
Kazuya Kariyama ◽  
Kazuhiro Nouso ◽  
Atsushi Hiraoka ◽  
Akiko Wakuta ◽  
Ayano Oonishi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Large Scale ◽  
Regression Coefficient ◽  
Information Criterion ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Highly Correlated ◽  
Survival Risk ◽  
Good Agreement

<b><i>Introduction:</i></b> The ALBI score is acknowledged as the gold standard for the assessment of liver function in patients with hepatocellular carcinoma (HCC). Unlike the Child-Pugh score, the ALBI score uses only objective parameters, albumin (Alb) and total bilirubin (T.Bil), enabling a better evaluation. However, the complex calculation of the ALBI score limits its applicability. Therefore, we developed a simplified ALBI score, based on data from a large-scale HCC database.We used the data of 5,249 naïve HCC cases registered in eight collaborating hospitals. <b><i>Methods:</i></b> We developed a new score, the EZ (Easy)-ALBI score, based on regression coefficients of Alb and T.Bil for survival risk in a multivariate Cox proportional hazard model. We also developed the EZ-ALBI grade and EZ-ALBI-T grade as alternative options for the ALBI grade and ALBI-T grade and evaluated their stratifying ability. <b><i>Results:</i></b> The equation used to calculate the EZ-ALBI score was simple {[T.Bil (mg/dL)] – [9 × Alb (g/dL)]}; this value highly correlated with the ALBI score (correlation coefficient, 0.981; <i>p</i> &#x3c; 0.0001). The correlation was preserved across different Barcelona clinic liver cancer grade scores (regression coefficient, 0.93–0.98) and across different hospitals (regression coefficient, 0.98–0.99), indicating good generalizability. Although a good agreement was observed between ALBI and EZ-ALBI, discrepancies were observed in patients with poor liver function (T.Bil, ≥3 mg/dL; regression coefficient, 0.877). The stratifying ability of EZ-ALBI grade and EZ-ALBI-T grade were good and their Akaike’s information criterion values (35,897 and 34,812, respectively) were comparable with those of ALBI grade and ALBI-T grade (35,914 and 34,816, respectively). <b><i>Conclusions:</i></b> The EZ-ALBI score, EZ-ALBI grade, and EZ-ALBI-T grade are useful, simple scores, which might replace the conventional ALBI score in the future.

scholarly journals Propagation of an MHD Shock in the Vicinity of a Magnetic Neutral Sheet

1980 ◽  
Vol 91 ◽  
pp. 323-326
Author(s):  
D. J. Mullan ◽  
R. S. Steinolfson
Keyword(s):  
Magnetic Field ◽  
Cosmic Rays ◽  
Solar Corona ◽  
Large Scale ◽  
Field Structure ◽  
Neutral Sheet ◽  
Solar Cosmic Rays ◽  
Magnetic Field Structure ◽  
Large Scale Magnetic Field ◽  
Highly Correlated

The acceleration of solar cosmic rays in association with certain solar flares is known to be highly correlated with the propagation of an MHD shock through the solar corona (Svestka, 1976). The spatial structure of the sources of solar cosmic rays will be determined by those regions of the corona which are accessible to the flare-induced shock. The regions to which the flare shock is permitted to propagate are determined by the large scale magnetic field structure in the corona. McIntosh (1972, 1979) has demonstrated that quiescent filaments form a single continuous feature (a “baseball stitch”) around the surface of the sun. It is known that helmet streamers overlie quiescent filaments (Pneuman, 1975), and these helmet streamers contain large magnetic neutral sheets which are oriented essentially radially. Hence the magnetic field structure in the low solar corona is characterized by a large-scale radial neutral sheet which weaves around the entire sun following the “baseball stitch”. There is therefore a high probability that as a shock propagates away from a flare, it will eventually encounter this large neutral sheet.

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