Timing of therapeutic interventions against infection-triggered encephalopathy syndrome: a scoping review of the pediatric literature

Our goal was to conduct a scoping review of the literature on the treatment of infection-triggered encephalopathy syndrome/acute encephalopathy in children, focusing on treatment targets and treatment initiation timing. We performed literature searches using PubMed for articles reporting treatments of infection-triggered encephalopathy syndrome/acute encephalopathy. We included articles describing specific treatments for acute encephalopathy with control groups. For the purpose of searching new therapies only experimentally tried in the case series, we also included case series studies without control groups in this review, if the studies contained at least two cases with clear treatment goals. Therapies were classified based on their mechanisms of action into brain protection therapy, immunotherapy, and other therapies. We operationally categorized the timing of treatment initiation as T1 (6–12 h), T2 (12–24 h), T3 (24–48 h), and T4 (>48 h) after the onset of seizures and/or impaired consciousness. Thirty articles were included in this review; no randomized control study was found. Eleven retrospective/historical cohort studies and five case–control studies included control groups with or without specific therapies or outcomes. The targeted conditions and treatment timing varied widely across studies. However, the following three points were suggested to be effective in multiple studies: (1) Careful seizure management and targeted temperature management within 12 h (T1) of onset of febrile seizure/prolonged impaired consciousness without multiple organ failure may reduce the development of acute encephalopathy with biphasic seizures and late reduced diffusion; (2) immunotherapy using corticosteroids, tocilizumab, or plasma exchange within 24 h (T1–T2) of onset of acute necrotizing encephalopathy may reduce sequelae; and (3) anakinra therapy and ketogenic diet demonstrate little evidence of neurologic sequelae reduction, but may reduce seizure frequency and allow for weaning from barbiturates, even when administered weeks (T4) after onset in children with febrile infection-related epilepsy syndrome. Although available studies have no solid evidence in the treatment of infection-triggered encephalopathy syndrome/acute encephalopathy, this scoping review lays the groundwork for future prospective clinical trials

Elasticity of Living Cells on a Microarray during the Early Stages of Adhesion Measured by Atomic Force Microscopy

The number distribution of the elastic modulus of fibroblast cells was successfully measured during the early stages of adhesion using an atomic force microscope (AFM) combined with a microarray as a substrate, which allowed us to arrange and culture cells so that a large number of cells could be measured in a short time period. We confirmed that the cells deposited in the wells of the microarray could be cultured for at least 12 h without any significant migration. Histograms of the Young's modulus, E, of the cells during the early stages of adhesion produced from force curve measurements of cells (n\cong300) cultured for 3–9 h were well fitted to a log-normal distribution function. With increasing incubation time, the average value of E increased significantly, while the standard deviation of the distribution remained almost constant. The results are discussed in terms of the cytoskeleton inside cells

Power-Law Stress and Creep Relaxations of Single Cells Measured by Colloidal Probe Atomic Force Microscopy

We measured stress and creep relaxations of mouse fibroblast cells arranged and cultured on a microarray, by colloidal probe atomic force microscopy (AFM). A hydrophobic monolayer coating of perfluorodecyltrichlorosilane (FDTS) on the surface of colloidal silica beads significantly reduced the adhesion force of live cells, compared with untreated beads. The rheological behaviors of cells were estimated by averaging several relaxation curves of cells measured by the AFM. Longer-time tailing of both stress and creep relaxation curves followed single power-law behavior over a time scale of 60 s, with exponents in the range 0.1–0.4, varying with cells. The results were in good agreement with previous measurements of the frequency-domain rheology of cells using the force modulation mode

Stress Relaxation Measurement of Fibroblast Cells with Atomic Force Microscopy

We measured the stress relaxation of mouse fibroblast NIH3T3 cells with an atomic force microscope (AFM) using a sharp silicon tip and a silica bead with a radius of ∼1 µm as an indenter. The decay of loading force was clearly observed in NIH3T3 cells at a small initial loading force of ∼0.4 nN and was well fitted to the stretched exponential function rather than to a single exponential function. The stretching exponent parameter was ∼0.5 for both indenters, indicating that the stress relaxation observed in NIH3T3 cells consisted of multiple relaxation processes. The time-domain AFM technique described in this report allows us to measure directly the relaxation process of living cells in a range from milliseconds to seconds

Nanoscale Visualization and Control of Ferroelectric Domains by Atomic Force Microscopy

The nanoscale visualization and control of domain structure with atomic force microscopy (AFM) in the ferroelectric crystal guanidinium aluminum sulfate hexahydrate is reported. The origin of the domain contrast in the topographic of AFM images is explained by the piezoelectric deformation of the crystal surface in the internal electric field. The domain structure was modified by applying a voltage to the conductive AFM tip. The dynamics of domain growth has been directly observed for the first time with a resolution of 10 nm