scholarly journals Quantitative Rapid Test for Detection and Monitoring of Active Pulmonary Tuberculosis in Nonhuman Primates

Biology ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1260
Author(s):  
Zijie Zhou ◽  
Anouk van Hooij ◽  
Richard Vervenne ◽  
Claudia C. Sombroek ◽  
Elisa M. Tjon Kon Fat ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Serum Proteins ◽  
Rhesus Macaques ◽  
Low Cost ◽  
Rapid Test ◽  
Serum Levels ◽  
Low Complexity ◽  
Lung Pathology ◽  
Pulmonary Tb ◽  
Active Pulmonary Tuberculosis

Nonhuman primates (NHPs) are relevant models to study the pathogenesis of tuberculosis (TB) and evaluate the potential of TB therapies, but rapid tools allowing diagnosis of active pulmonary TB in NHPs are lacking. This study investigates whether low complexity lateral flow assays utilizing upconverting reporter particles (UCP-LFAs) developed for rapid detection of human serum proteins can be applied to detect and monitor active pulmonary TB in NHPs. UCP-LFAs were used to assess serum proteins levels and changes in relation to the MTB challenge dosage, lung pathology, treatment, and disease outcome in experimentally MTB-infected macaques. Serum levels of SAA1, IP-10, and IL-6 showed a significant increase after MTB infection in rhesus macaques and correlated with disease severity as determined by pathology scoring. Moreover, these biomarkers could sensitively detect the reduction of bacterial levels in the lungs of macaques due to BCG vaccination or drug treatment. Quantitative measurements by rapid UCP-LFAs specific for SAA1, IP-10, and IL-6 in serum can be utilized to detect active progressive pulmonary TB in macaques. The UCP-LFAs thus offer a low-cost, convenient, and minimally invasive diagnostic tool that can be applied in studies on TB vaccine and drug development involving macaques.

scholarly journals Detection and Monitoring of Mycobacterium leprae Infection in Nine Banded Armadillos (Dasypus novemcinctus) Using a Quantitative Rapid Test

2021 ◽  
Vol 12 ◽  
Author(s):  
Zijie Zhou ◽  
Maria Pena ◽  
Anouk van Hooij ◽  
Louise Pierneef ◽  
Danielle de Jong ◽  
...  
Keyword(s):  
Low Cost ◽  
Bacterial Load ◽  
Rapid Test ◽  
Mycobacterium Leprae ◽  
Serum Levels ◽  
Antibody Detection ◽  
Quantitative Detection ◽  
Dasypus Novemcinctus ◽  
Asymptomatic Individuals ◽  
Antibody Kinetics

Leprosy is an infectious disease caused by Mycobacterium leprae with tropism for skin and peripheral nerves. Incessant transmission in endemic areas is still impeding elimination of leprosy. Although detection of M. leprae infection remains a challenge in asymptomatic individuals, the presence of antibodies specific for phenolglycolipid-I (PGL-I) correlate with bacterial load. Therefore, serosurveillance utilizing field-friendly tests detecting anti-PGL-I antibodies, can be applied to identify those who may transmit bacteria and to study (reduction of) M. leprae transmission. However, serology based on antibody detection cannot discriminate between past and present M. leprae infection in humans, nor can it detect individuals carrying low bacillary loads. In humans, anti-PGL-I IgM levels are long-lasting and usually detected in more individuals than anti-PGL-I IgG levels. Inherent to the characteristically long incubation time of leprosy, IgM/IgG relations (antibody kinetics) in leprosy patients and infected individuals are not completely clear. To investigate the antibody response directly after infection, we have measured antibody levels by ELISA, in longitudinal samples of experimentally M. leprae infected, susceptible nine-banded armadillos (Dasypus novemcinctus). In addition, we assessed the user- and field-friendly, low-cost lateral flow assay (LFA) utilizing upconverting reporter particles (UCP), developed for quantitative detection of human anti-PGL-I IgM (UCP-LFA), to detect treatment- or vaccination-induced changes in viable bacterial load. Our results show that serum levels of anti-PGL-I IgM, and to a lesser extent IgG, significantly increase soon after experimental M. leprae infection in armadillos. In view of leprosy phenotypes in armadillos, this animal model can provide useful insight into antibody kinetics in early infection in the various spectral forms of human leprosy. The UCP-LFA for quantitative detection of anti-PGL-I IgM allows monitoring the efficacy of vaccination and rifampin-treatment in the armadillo leprosy model, thereby providing a convenient tool to evaluate the effects of drugs and vaccines and new diagnostics.

Triticum aestivum Assay - A Useful Tool for Environmental Monitoring and Toxicity Assessment

2019 ◽  
Vol 47 (4) ◽  
pp. 1005-1018
Author(s):  
Alexandra JITĂREANU ◽  
Ioana-Cezara CABA ◽  
Adriana TRIFAN ◽  
Silvica PĂDUREANU ◽  
Luminița AGOROAEI
Keyword(s):  
Triticum Aestivum ◽  
Higher Plants ◽  
Low Cost ◽  
Environmental Pollutants ◽  
Rapid Test ◽  
Toxicity Assessment ◽  
Pollution Monitoring ◽  
Present Review ◽  
Digital Object Identifier ◽  
Biological Assays

The present review summarizes the literature data regarding the application of Triticum aestivum assay as an alternative method for toxicity assessment of environmental pollutants or potential therapeutic agents. Plant bioassays present several advantages among other biological assays (simplicity, low cost, rapid test activation, a wide array of assessment endpoints). They present a good correlation with animal and human cells models, and are a reliable tool for genotoxicity assessment. Furthermore, in the context of toxicology guidelines that promote the substitution of assays using animal models with other bioassays, genotoxicity assays using higher plants models have gained in popularity. The present review focuses on three major aspects regarding Triticum aestivum assay - its utility in environmental pollution monitoring, its application in genotoxicity assessment studies, and its application in phytotoxicity evaluation of nanomaterials.   ********* In press - Online First. Article has been peer reviewed, accepted for publication and published online without pagination. It will receive pagination when the issue will be ready for publishing as a complete number (Volume 47, Issue 4, 2019). The article is searchable and citable by Digital Object Identifier (DOI). DOI link will become active after the article will be included in the complete issue. *********

scholarly journals Recurrent Neural Network for Human Activity Recognition in Embedded Systems Using PPG and Accelerometer Data

Electronics ◽  
2021 ◽  
Vol 10 (14) ◽  
pp. 1715
Author(s):  
Michele Alessandrini ◽  
Giorgio Biagetti ◽  
Paolo Crippa ◽  
Laura Falaschetti ◽  
Claudio Turchetti
Keyword(s):  
Neural Network ◽  
Embedded System ◽  
Activity Recognition ◽  
Human Activity ◽  
Recurrent Neural Network ◽  
Low Cost ◽  
Low Complexity ◽  
Human Activity Recognition ◽  
Motion Artifacts ◽  
Accelerometer Data

Photoplethysmography (PPG) is a common and practical technique to detect human activity and other physiological parameters and is commonly implemented in wearable devices. However, the PPG signal is often severely corrupted by motion artifacts. The aim of this paper is to address the human activity recognition (HAR) task directly on the device, implementing a recurrent neural network (RNN) in a low cost, low power microcontroller, ensuring the required performance in terms of accuracy and low complexity. To reach this goal, (i) we first develop an RNN, which integrates PPG and tri-axial accelerometer data, where these data can be used to compensate motion artifacts in PPG in order to accurately detect human activity; (ii) then, we port the RNN to an embedded device, Cloud-JAM L4, based on an STM32 microcontroller, optimizing it to maintain an accuracy of over 95% while requiring modest computational power and memory resources. The experimental results show that such a system can be effectively implemented on a constrained-resource system, allowing the design of a fully autonomous wearable embedded system for human activity recognition and logging.

scholarly journals SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nanda Kishore Routhu ◽  
Narayanaiah Cheedarla ◽  
Venkata Satish Bollimpelli ◽  
Sailaja Gangadhara ◽  
Venkata Viswanadh Edara ◽  
...  
Keyword(s):  
Antibody Response ◽  
Antibody Titer ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Significant Loss ◽  
Lung Pathology ◽  
Live Virus ◽  
Suitable Candidate ◽  
Immune Pathology

AbstractThere is a great need for the development of vaccines that induce potent and long-lasting protective immunity against SARS-CoV-2. Multimeric display of the antigen combined with potent adjuvant can enhance the potency and longevity of the antibody response. The receptor binding domain (RBD) of the spike protein is a primary target of neutralizing antibodies. Here, we developed a trimeric form of the RBD and show that it induces a potent neutralizing antibody response against live virus with diverse effector functions and provides protection against SARS-CoV-2 challenge in mice and rhesus macaques. The trimeric form induces higher neutralizing antibody titer compared to monomer with as low as 1μg antigen dose. In mice, adjuvanting the protein with a TLR7/8 agonist formulation alum-3M-052 induces 100-fold higher neutralizing antibody titer and superior protection from infection compared to alum. SARS-CoV-2 infection causes significant loss of innate cells and pathology in the lung, and vaccination protects from changes in innate cells and lung pathology. These results demonstrate RBD trimer protein as a suitable candidate for vaccine against SARS-CoV-2.

scholarly journals A sand fly salivary protein vaccine shows efficacy against vector-transmitted cutaneous leishmaniasis in nonhuman primates

2015 ◽  
Vol 7 (290) ◽  
pp. 290ra90-290ra90 ◽  
Author(s):  
Fabiano Oliveira ◽  
Edgar Rowton ◽  
Hamide Aslan ◽  
Regis Gomes ◽  
Philip A. Castrovinci ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Nonhuman Primates ◽  
Mononuclear Cells ◽  
Rhesus Macaques ◽  
Parasite Burden ◽  
Salivary Protein ◽  
Sand Fly ◽  
Protein Vaccine ◽  
Peripheral Blood Mononuclear ◽  
Phlebotomus Duboscqi

Currently, there are no commercially available human vaccines against leishmaniasis. In rodents, cellular immunity to salivary proteins of sand fly vectors is associated to protection against leishmaniasis, making them worthy targets for further exploration as vaccines. We demonstrate that nonhuman primates (NHP) exposed to Phlebotomus duboscqi uninfected sand fly bites or immunized with salivary protein PdSP15 are protected against cutaneous leishmaniasis initiated by infected bites. Uninfected sand fly–exposed and 7 of 10 PdSP15-immunized rhesus macaques displayed a significant reduction in disease and parasite burden compared to controls. Protection correlated to the early appearance of Leishmania-specific CD4+IFN-γ+ lymphocytes, suggesting that immunity to saliva or PdSP15 augments the host immune response to the parasites while maintaining minimal pathology. Notably, the 30% unprotected PdSP15-immunized NHP developed neither immunity to PdSP15 nor an accelerated Leishmania-specific immunity. Sera and peripheral blood mononuclear cells from individuals naturally exposed to P. duboscqi bites recognized PdSP15, demonstrating its immunogenicity in humans. PdSP15 sequence and structure show no homology to mammalian proteins, further demonstrating its potential as a component of a vaccine for human leishmaniasis.

scholarly journals A20 DIAGNOSTIC ACCURACY OF A LOW COST, WIDELY AVAILABLE TEST STRIP FOR PREDICTING A POSITIVE FECAL CALPROTECTIN TEST

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 210-212
Author(s):  
R Trasolini ◽  
S Wong ◽  
B Salh
Keyword(s):  
Sample Size ◽  
Likelihood Ratio ◽  
Gold Standard ◽  
Low Cost ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Rapid Test ◽  
Test Strip ◽  
Fecal Calprotectin ◽  
Type I

Abstract Background Fecal calprotectin is a non-invasive test of colonic inflammation used for monitoring inflammatory bowel disease activity and for risk stratifying non-specific colonic symptoms. Calprotectin is a leukocyte specific enzyme. A similar test, leukocyte esterase is used to detect leukocytes in urine and is widely available as a low-cost point-of-care test strip. We hypothesize that an unmodified version of the urine test strip would be highly accurate in predicting a positive fecal calprotectin test in a real world sample of patients. Aims To explore a low cost, rapid alternative to the fecal calprotectin test Methods All inpatient and outpatient stool samples tested for calprotectin by the Vancouver General Hospital laboratory from February 2020 to November 2020 were included prospectively. Samples were simultaneously tested for fecal leukocyte esterase using an unmodified Roche Cobas Chemstrip urinalysis test strip by central lab personnel. An identical aliquot was sent to LifeLabs for calprotectin as per standard protocol. All samples were suspended in buffer using established laboratory protocols prior to testing. Fecal leukocyte esterase results were reported as 0–4+ based on visual interpretation, calprotectin results were reported as mcg/g of stool. REB review and approval was obtained prior to data collection. Sensitivity, Specificity and AUROC were calculated using Microsoft Excel and JROCFIT. Results 26 samples were collected. Using a fecal calprotectin greater than 120 mcg/g as a gold standard an AUROC of 0.89 (SE= .06) was calculated. A leukocyte esterase reading of 2+ or greater had the best test characteristics based on ROC curve analysis. Using this cutoff, 21/26 samples were concordant, giving an accuracy of 80.8%, sensitivity of 90.9% and specificity of 73.3%. Positive likelihood ratio was 8.07 and negative likelihood ratio was 0.29. Assuming an AUROC of 0.8, the sample size N=26 is 90% powered (β=0.9) to predict the true AUROC within 0.1 with a type I error rate of .05 (α<.05). Conclusions This study suggests application of a prepared stool sample to a urinalysis test strip gives a result highly predictive of a positive fecal calprotectin test. Further results are being collected prospectively to improve the robustness of these preliminary data. Secondary outcomes including comparison to endoscopy and biopsy results where available are planned if an adequate sample size can be accrued. Future studies justifying independent clinical use of leukocyte esterase would require a common gold standard comparator such as endoscopy. Fecal calprotectin testing is not universally insured and is not available as a rapid test strip. Use of fecal leukocyte esterase may reduce costs and shorten time to results if proven to be independently reliable. Funding Agencies None

scholarly journals Plasma Derived Exosomal Biomarkers of Exposure to Ionizing Radiation in Nonhuman Primates

2018 ◽  
Vol 19 (11) ◽  
pp. 3427 ◽  
Author(s):  
Amrita Cheema ◽  
Charles Hinzman ◽  
Khyati Mehta ◽  
Briana Hanlon ◽  
Melissa Garcia ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Nonhuman Primates ◽  
Rhesus Macaques ◽  
Ultra Performance Liquid Chromatography ◽  
Molecular Signature ◽  
Detection And Identification ◽  
Molecular Events ◽  
Plasma Metabolome ◽  
Radiation Induced ◽  
Hydroxyl Fatty Acids

Exposure to ionizing radiation induces a cascade of molecular events that ultimately impact endogenous metabolism. Qualitative and quantitative characterization of metabolomic profiles is a pragmatic approach to studying the risks of radiation exposure since it provides a phenotypic readout. Studies were conducted in irradiated nonhuman primates (NHP) to investigate metabolic changes in plasma and plasma-derived exosomes. Specifically, rhesus macaques (Macaca mulatta) were exposed to cobalt-60 gamma-radiation and plasma samples were collected prior to and after exposure to 5.8 Gy or 6.5 Gy radiation. Exosomes were isolated using ultracentrifugation and analyzed by untargeted profiling via ultra-performance liquid chromatography mass spectrometry (UPLC-MS) based metabolomic and lipidomic analyses, with the goal of identifying a molecular signature of irradiation. The enrichment of an exosomal fraction was confirmed using quantitative ELISA. Plasma profiling showed markers of dyslipidemia, inflammation and oxidative stress post-irradiation. Exosomal profiling, on the other hand, enabled detection and identification of low abundance metabolites that comprise exosomal cargo which would otherwise get obscured with plasma profiling. We discovered enrichment of different classes of metabolites including N-acyl-amino acids, Fatty Acid ester of Hydroxyl Fatty Acids (FAHFA’s), glycolipids and triglycerides as compared to the plasma metabolome composition with implications in mediation of systemic response to radiation induced stress signaling.

scholarly journals The Effect of 12 Hz Extremely Low-Frequency Electromagnetic Fields on Visual Memory of Male Macaque Monkeys

2021 ◽  
Author(s):  
Masoomeh Kazemi ◽  
◽  
Hamed Aliyari ◽  
Elaheh Tekieh ◽  
Hassan Tavacoli ◽  
...  
Keyword(s):  
Electromagnetic Fields ◽  
Visual Memory ◽  
Rhesus Macaques ◽  
Low Frequency ◽  
Serum Levels ◽  
Control Group ◽  
Behavioral Tests ◽  
Extremely Low Frequency ◽  
Before And After ◽  
Male Rhesus

Introduction: Today, humans leave in a world surrounded by electromagnetic fields. Numerous studies have been carried out to discover the biological, physiological, and behavioral effects of electromagnetic fields on humans and animals. Given the biological similarities between monkeys and humans, the goal of the present research was to examine Visual Memory (VM), hormonal, genomic, and anatomic changes, and changes of the amygdala function in the male rhesus macaques who exposed to extremely low-frequency magnetic fields (ELF/MF). Materials and methods: Four male Rhesus Macaques (Macaca mulatta) were used. For the behavioral tests the animals were needed to be fasting for 17 hours, and for the behavioral tests such as visual memory, cooperation of the animal was necessary. Using the radiation protocol, two of the monkeys were exposed to 12-Hz electromagnetic fields with a magnitude of 0.7 microtesla (electromagnetic radiation) four hours a day for a month. Before and after the exposure, a visual memory test was conducted using a coated device (visible reward) on a movable stand. Ten mL of blood was obtained from the femoral artery of the monkeys and half of it was used to examine cortisol serum levels using MyBioSource kits (made in the USA). The other half of blood samples were used to extract lymphocytes for assaying expressions of Glucocorticoid Receptor (GR) genes before and after radiation using the PCR method. Anatomic studies of the amygdala were carried out based on pre- and post-radiation Magnetic Resonance Imaging (MRI). Findings: Research results indicated that visual memory in male primates increased significantly at the 12Hz frequency. Hormonal analysis at the 12Hz frequency showed a decrease in cortisol serum levels. However, visual memory and serum cortisol levels did not change considerably in male primates in the control group. There was no considerable amygdala volumetric difference at the 12 Hz frequency. The expression of the GR genes decreased at 12Hz compared to the control group. Conclusion: In short, these results indicated that ELF may have a beneficial value for memory enhancement as indicated by the fact that exposure to the 12 HZ ELF can enhance visual memory. This may be due to a decrease in plasma cortisol, and/or expression of GR genes. Moreover, direct involvement of the amygdala in this regard cannot be recommended.

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