Biomimetic Microcavity Interface for Label-free Capture of Pathogens in Fluid Bloodstream by Vortical Crossflow Filtration

Nanoscale ◽  
2021 ◽  
Author(s):  
Liyuan Zheng ◽  
Xiaobo Zheng ◽  
Shanshan Yuan ◽  
Weide Xu ◽  
Changhuan Zhang ◽  
...  
Keyword(s):  
Disease Severity ◽  
Microbial Pathogens ◽  
Major Contributor ◽  
Label Free ◽  
Bacterial Sepsis ◽  
Crossflow Filtration ◽  
Pathogen Load

Bacterial sepsis is a lethal disease triggered by microbial pathogens. The blood pathogen load is a major contributor to both disease severity and mortality in patients with sepsis blood. So...

scholarly journals Infectious Causes of Cholesteatoma and Treatment of Infected Ossicles prior to Reimplantation by Hydrostatic High-Pressure Inactivation

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Wycliffe Omurwa Masanta ◽  
Rebecca Hinz ◽  
Andreas Erich Zautner
Keyword(s):  
Hydrostatic Pressure ◽  
High Hydrostatic Pressure ◽  
Surgical Intervention ◽  
Pressure Level ◽  
Microbial Pathogens ◽  
Recent Experimental Data ◽  
Chronic Infections ◽  
Planktonic Bacteria ◽  
Pathogen Load ◽  
High Hydrostatic Pressure Treatment

Chronic inflammation, which is caused by recurrent infections, is one of the factors contributing to the pathogenesis of cholesteatoma. If reimplantation of autologous ossicles after a surgical intervention is intended, inactivation of planktonic bacteria and biofilms is desirable. High hydrostatic pressure treatment is a procedure, which has been used to inactivate cholesteatoma cells on ossicles. Here we discuss the potential inactivating effect of high hydrostatic pressure on microbial pathogens including biofilms. Recent experimental data suggest an incomplete inactivation at a pressure level, which is tolerable for the bone substance of ossicles and results at least in a considerable reduction of pathogen load. Further studies are necessary to access how far this quantitative reduction of pathogens is sufficient to prevent ongoing chronic infections, for example, due to forming of biofilms.

scholarly journals The role of HMGB1 in invasive Candida albicans infection

2020 ◽  
Author(s):  
Jiaojiao Wang ◽  
Chuanxin Wu ◽  
Yunying Wang ◽  
Chongxiang Chen ◽  
Jing Cheng ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Fungal Infection ◽  
Disease Severity ◽  
Therapeutic Target ◽  
Ethyl Pyruvate ◽  
Bacterial Sepsis ◽  
Infection Group ◽  
Protein Levels ◽  
Tnf Α

Abstract Background: High mobility group box 1 (HMGB1), an important “late” inflammatory mediator, is a therapeutic target for bacterial sepsis. Ethyl pyruvate (EP) has anti-inflammatory effects, and prevents bacterial sepsis by decreasing HMGB1 levels. However, the role of HMGB1 in fungal sepsis is still unclear. Therefore, we investigated HMGB1 mRNA and protein levels in serum and tissue from patients and mice with invasive C. albicans infection. We explored the anti-HMGB1 effects of EP, which may be of benefit in the diagnosis and treatment of invasive C. albicans infections. Methods: We measured serum HMGB1 mRNA and protein levels in four different patient groups: 23 control subjects (group 1), 35 patients with sepsis without fungal infection (group 2), 35 patients with severe sepsis without fungal infection (group 3), and 23 patients with severe sepsis with C. albicans infection (group 4). We collected clinical indices to estimate correlations between HMGB1 levels and disease severity. Furthermore, we experimentally stimulated mice with C. albicans and C. albicans + EP, and examined HMGB1 mRNA and protein levels from serum and tissue. We determined liver and kidney functions, investigated pathological changes in tissues and assessed mortality. We also investigated serum levels of the proinflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in these animals. Results: Serum HMGB1 mRNA and protein levels in patients with severe sepsis with C. albicans infection were elevated. Increased HMGB1 levels were correlated with procalcitonin (PCT), C-reactive protein (CRP), 1,3-β-D-Glucan (BDG) and C. albicans sepsis severity. HMGB1 mRNA and protein levels in serum and tissues were significantly increased within seven days after mice were infected with C. albicans. The administration of EP inhibited HMGB1 levels, decreased tissue damage, increased survival rates and inhibited the release of TNF-α and IL-6.Conclusions: Increased HMGB1 levels in patients with severe sepsis with C. albicans infection were positively correlated with PCT, CRP, BDG, and disease severity. EP prevented C. albicans lethality by decreasing HMGB1 expression and release. We suggest that HMGB1 plays a vital role in invasive C. albicans infections and may provide an effective diagnostic and therapeutic target for such infections in clinical settings.

scholarly journals Forecasting COVID-19 Severity by Intelligent Optical Fingerprinting of Blood Samples

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1309
Author(s):  
Simão P. Faria ◽  
Cristiana Carpinteiro ◽  
Vanessa Pinto ◽  
Sandra M. Rodrigues ◽  
José Alves ◽  
...  
Keyword(s):  
Disease Severity ◽  
Clinical Decision Making ◽  
Clinical Laboratory ◽  
Low Cost ◽  
Clinical Decision ◽  
Strongly Correlated ◽  
Label Free ◽  
Ensemble Machine Learning ◽  
Signal Features ◽  
Machine Learning Model

Forecasting COVID-19 disease severity is key to supporting clinical decision making and assisting resource allocation, particularly in intensive care units (ICUs). Here, we investigated the utility of time- and frequency-related features of the backscattered signal of serum patient samples to predict COVID-19 disease severity immediately after diagnosis. ICU admission was the primary outcome used to define disease severity. We developed a stacking ensemble machine learning model including the backscattered signal features (optical fingerprint), patient comorbidities, and age (AUROC = 0.80), which significantly outperformed the predictive value of clinical and laboratory variables available at hospital admission (AUROC = 0.71). The information derived from patient optical fingerprints was not strongly correlated with any clinical/laboratory variable, suggesting that optical fingerprinting brings unique information for COVID-19 severity risk assessment. Optical fingerprinting is a label-free, real-time, and low-cost technology that can be easily integrated as a front-line tool to facilitate the triage and clinical management of COVID-19 patients.

scholarly journals Proteomic analysis of thePseudomonas aeruginosairon starvation response reveals PrrF sRNA-dependent regulation of amino acid metabolism, iron-sulfur cluster biogenesis, motility, and zinc homeostasis

2018 ◽  
Author(s):  
Cassandra E. Nelson ◽  
Weiliang Huang ◽  
Luke K. Brewer ◽  
Angela T. Nguyen ◽  
Maureen A. Kane ◽  
...  
Keyword(s):  
Amino Acid ◽  
Opportunistic Pathogen ◽  
Zinc Homeostasis ◽  
Microbial Pathogens ◽  
Label Free ◽  
Iron Starvation ◽  
Iron Sulfur Cluster ◽  
Starvation Response ◽  
Iron Sulfur ◽  
Small Regulatory Rnas

ABSTRACTIron is a critical nutrient for most microbial pathogens, and the innate immune system exploits this requirement by sequestering iron and other metals through a process termed nutritional immunity. The opportunistic pathogenPseudomonas aeruginosaprovides a model system for understanding the microbial response to host iron depletion, as this organism exhibits a high requirement for iron as well as an exquisite ability to overcome iron deprivation during infection. Hallmarks ofP. aeruginosa’siron starvation response include the induction of multiple high affinity iron acquisition systems and an “iron sparing response” that is post-transcriptionally mediated by the PrrF small regulatory RNAs (sRNAs). Here, we used liquid chromatography-tandem mass spectrometry to conduct label-free proteomics of theP. aeruginosairon starvation response, revealing several iron-regulated processes that have not been previously described. Iron starvation induced multiple proteins involved in branched chain and aromatic amino acid catabolism, providing the capacity for iron-independent entry of carbons into the TCA cycle. Proteins involved in sulfur assimilation and cysteine biosynthesis were reduced upon iron starvation, while proteins involved in iron-sulfur cluster biogenesis were paradoxically increased, highlighting the central role of iron inP. aeruginosametabolism. Iron starvation also resulted in changes in the expression of several zinc-responsive proteins, as well as the first experimental evidence for increased levels of twitching motility proteins upon iron starvation. Subsequent proteomics analyses demonstrated that the PrrF sRNAs were required for iron regulation of many of these newly-identified proteins, and we identified PrrF complementarity with mRNAs encoding key iron-regulated proteins involved in amino acid metabolism, iron-sulfur biogenesis, and zinc homeostasis. Combined, these results provide the most comprehensive view of theP. aeruginosairon starvation response to date and outline novel roles for the PrrF sRNAs in theP. aeruginosairon sparing response and pathogenesis.AUTHOR SUMMARYIron is central for the metabolism of almost all microbial pathogens, and as such this element is sequestered by the host innate immune system to restrict microbial growth. Defining the response of microbial pathogens to iron starvation is therefore critical for understanding how pathogens colonize and propagate within the host. The opportunistic pathogenPseudomonas aeruginosa, which causes significant morbidity and mortality in compromised individuals, provides an excellent model for studying this response due to its high requirement for iron yet well-documented ability to overcome iron starvation. Here we used label-free proteomics to investigate theP. aeruginosairon starvation response, revealing a broad landscape of metabolic and metal homeostasis changes that have not previously been described. We further provide evidence that many of these processes are regulated through the iron responsive PrrF small regulatory RNAs, which are integral toP. aeruginosairon homeostasis and virulence. These results demonstrate the power of proteomics for defining stress responses of microbial pathogens, and they provide the most comprehensive analysis to date of theP. aeruginosairon starvation response.

scholarly journals Kinetics of SARS-CoV-2 Antibody Avidity Maturation and Association with Disease Severity

2020 ◽  
Author(s):  
Yiqi Ruben Luo ◽  
Indrani Chakraborty ◽  
Cassandra Yun ◽  
Alan H.B. Wu ◽  
Kara Lake Lynch
Keyword(s):  
Disease Severity ◽  
Symptom Onset ◽  
Strong Correlation ◽  
Label Free ◽  
Antibody Avidity ◽  
Mild Disease ◽  
Avidity Assay ◽  
Igg Avidity ◽  
Kinetics Of ◽  
Avidity Maturation

The kinetics of IgG avidity maturation during SARS-CoV-2 infection was studied. The IgG avidity assay used a novel label-free immunoassay technology. It was found that there was a strong correlation between IgG avidity and days since symptom onset, and peak readings were significantly higher in severe than mild disease cases.

scholarly journals A New Method for Optimizing Sepsis Therapy by Nivolumab and Meropenem Combination: Importance of Early Intervention and CTL Reinvigoration Rate as a Response Marker

2021 ◽  
Vol 12 ◽  
Author(s):  
Avi Gillis ◽  
Anat Ben Yaacov ◽  
Zvia Agur
Keyword(s):  
Fitness Function ◽  
Bacterial Sepsis ◽  
Personal Benefit ◽  
Pathogen Elimination ◽  
Pathogen Load ◽  
Maximum Benefit ◽  
Antibiotic Drug ◽  
Sepsis Therapy ◽  
Drug Regimens ◽  
Cellular Immune

Background: Recently, there has been a growing interest in applying immune checkpoint blockers (ICBs), so far used to treat cancer, to patients with bacterial sepsis. We aimed to develop a method for predicting the personal benefit of potential treatments for sepsis, and to apply it to therapy by meropenem, an antibiotic drug, and nivolumab, a programmed cell death-1 (PD-1) pathway inhibitor.Methods: We defined an optimization problem as a concise framework of treatment aims and formulated a fitness function for grading sepsis treatments according to their success in accomplishing the pre-defined aims. We developed a mathematical model for the interactions between the pathogen, the cellular immune system and the drugs, whose simulations under diverse combined meropenem and nivolumab schedules, and calculation of the fitness function for each schedule served to plot the fitness landscapes for each set of treatments and personal patient parameters.Results: Results show that treatment by meropenem and nivolumab has maximum benefit if the interval between the onset of the two drugs does not exceed a dose-dependent threshold, beyond which the benefit drops sharply. However, a second nivolumab application, within 7–10 days after the first, can extinguish a pathogen which the first nivolumab application failed to remove. The utility of increasing nivolumab total dose above 6 mg/kg is contingent on the patient's personal immune attributes, notably, the reinvigoration rate of exhausted CTLs and the overall suppression rates of functional CTLs. A baseline pathogen load, higher than 5,000 CFU/μL, precludes successful nivolumab and meropenem combination therapy, whereas when the initial load is lower than 3,000 CFU/μL, meropenem monotherapy suffices for removing the pathogen.Discussion: Our study shows that early administration of nivolumab, 6 mg/kg, in combination with antibiotics, can alleviate bacterial sepsis in cases where antibiotics alone are insufficient and the initial pathogen load is not too high. The study pinpoints the role of precision medicine in sepsis, suggesting that personalized therapy by ICBs can improve pathogen elimination and dampen immunosuppression. Our results highlight the importance in using reliable markers for classifying patients according to their predicted response and provides a valuable tool in personalizing the drug regimens for patients with sepsis.

scholarly journals Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Avidity Maturation and Association with Disease Severity

2020 ◽  
Author(s):  
Yiqi Ruben Luo ◽  
Indrani Chakraborty ◽  
Cassandra Yun ◽  
Alan H B Wu ◽  
Kara L Lynch
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Disease Severity ◽  
Symptom Onset ◽  
Strong Correlation ◽  
Label Free ◽  
Antibody Avidity ◽  
Mild Disease ◽  
Igg Avidity ◽  
Kinetics Of ◽  
Avidity Maturation

Abstract The kinetics of IgG avidity maturation during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was studied. The IgG avidity assay, using a novel label-free immunoassay technology, revealed a strong correlation between IgG avidity and days since symptom onset. Peak readings were significantly higher in severe than mild disease cases.

Label-free, mass-sensitive single-molecule imaging using interferometric scattering microscopy

2020 ◽  
Author(s):  
Nikolas Hundt
Keyword(s):  
Single Molecule ◽  
Cellular Systems ◽  
Single Molecule Imaging ◽  
Label Free ◽  
Measurement Sensitivity ◽  
Mass Distributions ◽  
Quantitative Measurements ◽  
Contrast Mechanism ◽  
Cellular Components ◽  
Scattering Signal

Abstract Single-molecule imaging has mostly been restricted to the use of fluorescence labelling as a contrast mechanism due to its superior ability to visualise molecules of interest on top of an overwhelming background of other molecules. Recently, interferometric scattering (iSCAT) microscopy has demonstrated the detection and imaging of single biomolecules based on light scattering without the need for fluorescent labels. Significant improvements in measurement sensitivity combined with a dependence of scattering signal on object size have led to the development of mass photometry, a technique that measures the mass of individual molecules and thereby determines mass distributions of biomolecule samples in solution. The experimental simplicity of mass photometry makes it a powerful tool to analyse biomolecular equilibria quantitatively with low sample consumption within minutes. When used for label-free imaging of reconstituted or cellular systems, the strict size-dependence of the iSCAT signal enables quantitative measurements of processes at size scales reaching from single-molecule observations during complex assembly up to mesoscopic dynamics of cellular components and extracellular protrusions. In this review, I would like to introduce the principles of this emerging imaging technology and discuss examples that show how mass-sensitive iSCAT can be used as a strong complement to other routine techniques in biochemistry.

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