β1-blocker in sepsis Hasegawa, Daisuke; Sato, Ryota; Nishida, Osamu
Journal of intensive care,
05/2021, Letnik:
9, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The use of ultrashort-acting β1-blockers recently has attracted attention in septic patients with non-compensatory tachycardia. We summarized the metabolic and hemodynamic effects and the clinical ...evidence of ultrashort-acting β1-blockers.
A recent meta-analysis showed that ultrashort-acting β1-blockers reduced the mortality in septic patients with persistent tachycardia. However, its mechanism to improve mortality is not fully understood yet. We often use lactate as a marker of oxygen delivery, but an impaired oxygen use rather than reduced oxygen delivery has been recently proposed as a more reasonable explanation of hyperlactatemia in patients with sepsis, leading to a question of whether β1-blockers affect metabolic systems. While the stimulation of the β2-receptor accelerates glycolysis and lactate production, the role of β1-blocker in lactate production remains unclear and studies investigating the role of β1-blockers in lactate kinetics are warranted. A meta-analysis also reported that ultrashort-acting β1-blockers increased stroke volume index, while it reduced heart rate, resulting in unchanged cardiac index, mean arterial pressure, and norepinephrine requirement at 24 h, leading to an improvement of cardiovascular efficiency. On the other hand, a recent study reported that heart rate reduction using fast esmolol titration in the very early phase of septic shock caused hemodynamic instability, suggesting that ultrashort-acting β1-blockers should be started only after completing initial resuscitation. While many clinicians still do not feel comfortable controlling sinus tachycardia, one randomized controlled trial in which the majority had sinus tachycardia suggested the mortality benefit of ultrashort-acting β1-blockers. Therefore, it still deems to be reasonable to control sinus tachycardia with ultrashort-acting β1-blockers after completing initial resuscitation.
Accumulating evidence is supporting the use of ultrashort-acting β1-blockers while larger randomized controlled trials to clarify the effect of ultrashort-acting β1-blockers are still warranted.
Purpose: Quantitative susceptibility mapping (QSM) is useful for obtaining biological information. To calculate susceptibility distribution, it is necessary to calculate the local field caused by the ...differences of susceptibility between the tissues. The local field can be obtained by removing a background field from a total field acquired by MR phase image. Conventional approaches based on spherical mean value (SMV) filtering, which are widely used for background field calculations, fail to calculate the background field of the brain surface region corresponding to the radius of the SMV kernel, and consequently cannot calculate the QSM of the brain surface region. Accordingly, a new method calculating the local field by expansively removing the background field is proposed for whole brain QSM.Methods: The proposed method consists of two steps. First, the background field of the brain surface is calculated from the total field using a locally polynomial approximation of spherical harmonics. Second, the whole brain local field is calculated by SMV filtering with a constraint term of the background field of the brain surface. The parameters of the approximation were optimized to reduce calculation errors through simulations using both a numerical phantom and a measured human brain. Performance of the proposed method with the optimized parameters was quantitatively and visually compared with conventional methods in an experiment of five healthy volunteers.Results: The proposed method showed the accurate local field over the expanded brain region in the simulation studies. It also showed consistent QSM with conventional methods inside of the brain surface and showed clear vein structures on the brain surface.Conclusion: The proposed method enables accurate calculation of whole brain QSM without eroding the brain surface region while maintaining same values inside of the brain surface as the conventional methods.
In snow-covered areas, slope failures induced by snowmelt water may occur. In this study, we attempted to develop a warning method for snowmelt disasters using the effective rainfall index, which ...reflects the analyzed snowmelt amount (hereinafter referred to as the effective snowmelt index) and we verified the appropriate half-life of the effective snowmelt index by comparing it with the observation results of groundwater response. As a result, it was confirmed that a strong correlation between them under the conditions that the half-life of the index was set from 24 hour to 96 hour. In addition, through case studies, we found that the warning method using the effective snowmelt index and snow depth as evaluation indices could effectively provide warning of snowmelt disasters.
Objectives
Voxel-based morphometry (VBM) is widely used to quantify the progression of Alzheimer’s disease (AD), but improvement is still needed for accurate early diagnosis. We evaluated the ...feasibility of a novel diagnosis index for early diagnosis of AD based on quantitative susceptibility mapping (QSM) and VBM.
Methods
Thirty-seven patients with AD, 24 patients with mild cognitive impairment (MCI) due to AD, and 36 cognitively normal (NC) subjects from four centers were included. A hybrid sequence was performed by using 3-T MRI with a 3D multi-echo GRE sequence to obtain both a T1-weighted image for VBM and phase images for QSM. The index was calculated from specific voxels in QSM and VBM images by using a linear support vector machine. The method of voxel extraction was optimized to maximize diagnostic accuracy, and the optimized index was compared with the conventional VBM-based index using receiver operating characteristic analysis.
Results
The index was optimal when voxels were extracted as increased susceptibility (AD > NC) in the parietal lobe and decreased gray matter volume (AD < NC) in the limbic system. The optimized proposed index showed excellent performance for discrimination between AD and NC (AUC = 0.94,
p
= 1.1 × 10
−10
) and good performance for MCI and NC (AUC = 0.87,
p
= 1.8 × 10
−6
), but poor performance for AD and MCI (AUC = 0.68,
p
= 0.018). Compared with the conventional index, AUCs were improved for all cases, especially for MCI and NC (
p
< 0.05).
Conclusions
In this preliminary study, the proposed index based on QSM and VBM improved the diagnostic performance between MCI and NC groups compared with the VBM-based index.
Key Points
•
We developed a novel diagnostic index for Alzheimer’s disease based on quantitative susceptibility mapping (QSM) and voxel-based morphometry (VBM).
•
QSM and VBM images can be acquired simultaneously in a single sequence with little increasing scan time.
•
In this preliminary study, the proposed diagnostic index improved the discriminative performance between mild cognitive impairment and normal control groups compared with the conventional VBM-based index.
Single-molecule imaging (SMI) has been widely utilized to investigate biomolecular dynamics and protein–protein interactions in living cells. However, multicolor SMI of intracellular proteins is ...challenging because of high background signals and other limitations of current fluorescence labeling approaches. To achieve reproducible intracellular SMI, a labeling probe ensuring both efficient membrane permeability and minimal non-specific binding to cell components is essential. We developed near-infrared fluorescent probes for protein labeling that specifically bind to a mutant β-lactamase tag. By structural fine-tuning of cell permeability and minimized non-specific binding, SiRcB4 enabled multicolor SMI in combination with a HaloTag-based red-fluorescent probe. Upon addition of both chemical probes at sub-nanomolar concentrations, single-molecule imaging revealed the dynamics of TLR4 and its adaptor protein, TIRAP, which are involved in the innate immune system. Statistical analysis of the quantitative properties and time-lapse changes in dynamics revealed a protein–protein interaction in response to ligand stimulation.
Spinel ferrite MFe2O4 (M = Mn, Fe, Co, Ni, and Zn) nanoparticles, coordinated with oleylamine, oleic acid, and trioctylphosphine oxide, were effectively synthesized by the microwave-assisted rapid ...synthesis in 1-dodecanol. Spinel ferrite nanoparticles were structurally analyzed using HRTEM, SAED, HAADF-STEM, XRD, XRF, XPS, and EXAFS measurements, which suggested that MFe2O4 nanoparticles have 3.2–4.3 nm in diameter and a spinel cubic structure with space group Fd3̅m. The metal composition retains an initially charged molar ratio (Fe: M = 2: 1), and both corresponding elements exist within a particle. EXAFS analysis performed quantitative determination of cation distribution in the tetrahedral and octahedral sites of the spinel structure to gain a deep insight into the influence of the cation distribution (i.e., the degree of inversion) to their magnetic properties. Compared with the magnetic properties of the bulk spinel structure, small spinel ferrite particles at nanoscale showed some promising applications for the magnetic data storage, catalysts, sensors, and ferrofluids, due to the significant effect of their particle sizes, surface coordinating environments, and the cation distributions.
Cell segmentation from microscopic images is conventionally used to investigate cell morphology. However, the time expense for manual segmentation becomes extreme with increasing numbers of cells to ...be analyzed. Recent progress in automated image analysis techniques can facilitate efficient and accurate cell segmentation in wide-range confocal images. Pavement cells, which mainly comprise the epidermal tissue of plant leaves, show jigsaw puzzle-like shapes and provide a model for elucidating the mechanisms underlying the complex morphology of plant cells. This mini-review demonstrates the effectiveness of using a confocal image processing pipeline for morphometric analysis and mechanical simulation using Arabidopsis thaliana cotyledon pavement cells as an example. We examined A. thaliana cotyledon surfaces using wide-range confocal images and used an image processing pipeline in ImageJ software to extract epidermal cell contours. We then used the segmented epidermal cell images to provide examples of how this information can be used for morphometry and mechanical simulation. The use of this high-throughput segmentation method is not limited to plant epidermal tissue and can be applied to various biological materials. Therefore, our approach to microscopic image analysis will hopefully contribute to the advancement of quantitative cell morphology research.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and multiple organ damage. Toll-like receptor 7 (TLR7), an innate immune RNA sensor expressed in ...monocytes/macrophages, dendritic cells (DCs), and B cells, promotes disease progression. However, little is known about the cellular mechanisms through which TLR7 drives lupus nephritis. Here, we show that the anti-mouse TLR7 mAb, but not anti-TLR9 mAb, protected lupus-prone NZBWF1 mice from nephritis. The anti-TLR7 mAb reduced IgG deposition in glomeruli by inhibiting the production of autoantibodies to the RNA-associated antigens. We found a disease-associated increase in Ly6C
patrolling monocytes that expressed high levels of TLR7 and had upregulated expression of lupus-associated IL-10, CD115, CD31, and TNFSF15 in NZBWF1 mice. Anti-TLR7 mAb abolished this lupus-associated increase in patrolling monocytes in the circulation, spleen, and glomeruli. These results suggested that TLR7 drives autoantibody production and lupus-associated monocytosis in NZBWF1 mice and, that anti-TLR7 mAb is a promising therapeutic tool targeting B cells and monocytes/macrophages.
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