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Super-Low Dose Lipopolysaccharide Dysregulates Neutrophil Migratory Decision-Making.

ABSTRACT: Neutrophils are the first responders to infection and play a pivotal role in many inflammatory diseases, including sepsis. Recent studies have shown that lipopolysaccharide (LPS), a classical pattern recognition molecule, dynamically programs innate immune responses. In this study, we show that pre-treatment with super-low levels of LPS [1 ng/mL] significantly dysregulate neutrophil migratory phenotypes, including spontaneous migration and altering neutrophil decision-making. To quantify neutrophil migratory decision-making with single-cell resolution, we developed a novel microfluidic competitive chemotaxis-chip (μC3) that exposes cells in a central channel to competing chemoattractant gradients. In this reductionist approach, we use two chemoattractants: a pro-resolution (N-Formyl-Met-Leu-Phe, fMLP) and pro-inflammatory (Leukotriene B4, LTB4) chemoattractant to model how a neutrophil makes a decision to move toward an end target chemoattractant (e.g., bacterial infection) vs. an intermediary chemoattractant (e.g., inflammatory signal). We demonstrate that naïve neutrophils migrate toward the primary end target signal in higher percentages than toward the secondary intermediary signal. As expected, we found that training with high dose LPS [100 ng/mL] influences a higher percentage of neutrophils to migrate toward the end target signal, while reducing the percentage of neutrophils that migrate toward the intermediary signal. Surprisingly, super-low dose LPS [1 ng/mL] significantly changes the ratios of migrating cells and an increased percentage of cells migrate toward the intermediary signal. Significantly, there was also an increase in the numbers of spontaneously migrating neutrophils after treatment with super-low dose LPS. These results shed light onto the directional migratory decision-making of neutrophils exposed to inflammatory training signals. Understanding these mechanisms may lead to the development of pro-resolution therapies that correct the neutrophil compass and reduce off-target organ damage.

SUBMITTER: Boribong BP

PROVIDER: S-EPMC6422936 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDecisions about lung cancer screening are inherently complex and create a need for methods to convey the risks and benefits of screening to patients.Research questionWhat kind of decision aids or tools are available to support shared decision-making for lung cancer screening? What is the current evidence for the effectiveness, acceptability, and feasibility of those tools?Study design and methodsWe conducted a systematic review of studies and searched PubMed, MEDLINE, EMBASE, Cochrane Clinical Trials Register, and ClinicalTrials.gov from inception to December 2019 for studies that evaluated the effectiveness and acceptability of tools to promote shared decision-making for patients who are considering lung cancer screening.ResultsAfter screening 2,427 records, we included one randomized control trial, two observational studies, 11 before/after studies of a decision aid or an educational tool. Fifteen distinct tools in various formats were evaluated in 14 studies. Most studies were of fair quality. Studies reported improvement in patients' knowledge of lung cancer screening (n = 9 studies), but improvements in specific areas of knowledge were inconsistent. Decisional conflict was low or reduced after the administration of the tools (n = 7 studies). The acceptability of tools was rated as "high" by patients (n = 7 studies) and physicians (n = 1 study). Low dose CT scan completion rates varied among studies (n = 6 studies).InterpretationEvidence from 14 studies suggests that some elements of existing tools for lung cancer screening may help to prepare patients for decision-making by improving knowledge and reducing decisional conflict. Such tools generally are acceptable to patients and providers. Further studies that use consistent measures and reporting methods and assess relevant decisional and clinical outcomes are needed to determine the comparative effectiveness and feasibility of implementation of these tools.Clinical trial registrationPROSPERO 2018 CRD4201874814.

Project description:IntroductionThe vaccine distribution for the COVID-19 is a multicriteria decision-making (MCDM) problem based on three issues, namely, identification of different distribution criteria, importance criteria and data variation. Thus, the Pythagorean fuzzy decision by opinion score method (PFDOSM) for prioritising vaccine recipients is the correct approach because it utilises the most powerful MCDM ranking method. However, PFDOSM weighs the criteria values of each alternative implicitly, which is limited to explicitly weighting each criterion. In view of solving this theoretical issue, the fuzzy-weighted zero-inconsistency (FWZIC) can be used as a powerful weighting MCDM method to provide explicit weights for a criteria set with zero inconstancy. However, FWZIC is based on the triangular fuzzy number that is limited in solving the vagueness related to the aforementioned theoretical issues.ObjectivesThis research presents a novel homogeneous Pythagorean fuzzy framework for distributing the COVID-19 vaccine dose by integrating a new formulation of the PFWZIC and PFDOSM methods.MethodsThe methodology is divided into two phases. Firstly, an augmented dataset was generated that included 300 recipients based on five COVID-19 vaccine distribution criteria (i.e., vaccine recipient memberships, chronic disease conditions, age, geographic location severity and disabilities). Then, a decision matrix was constructed on the basis of an intersection of the 'recipients list' and 'COVID-19 distribution criteria'. Then, the MCDM methods were integrated. An extended PFWZIC was developed, followed by the development of PFDOSM.Results(1) PFWZIC effectively weighted the vaccine distribution criteria. (2) The PFDOSM-based group prioritisation was considered in the final distribution result. (3) The prioritisation ranks of the vaccine recipients were subject to a systematic ranking that is supported by high correlation results over nine scenarios of the changing criteria weights values.ConclusionThe findings of this study are expected to ensuring equitable protection against COVID-19 and thus help accelerate vaccine progress worldwide.

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Super-Low Dose Lipopolysaccharide Dysregulates Neutrophil Migratory Decision-Making.

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