To investigate how the biofilm three-dimensional (3D) architecture influences in situ pH distribution patterns on the enamel surface. Biofilms were formed on human tooth enamel in the presence of 1% sucrose or 0.5%glucose plus 0.5%fructose. At specific time points, biofilms were exposed to a neutral pH buffer to mimic the buffering of saliva and subsequently pulsed with 1% glucose to induce re-acidification. Simultaneous 3D pH mapping and architecture of intact biofilms was performed using two-photon confocal microscopy. The enamel surface and mineral content characteristics were examined successively via optical profilometry and microradiography analyses. Sucrose-mediated biofilm formation created spatial heterogeneities manifested by complex networks of bacterial clusters (microcolonies). Acidic regions (pH<5.5) were found only in the interior of microcolonies, which impedes rapid neutralization (taking more than 120 min for neutralization). Glucose exposure rapidly re-created the acidic niches, indicating formation of diffusion barriers associated with microcolonies structure. Enamel demineralization (white spots), rougher surface, deeper lesion and more mineral loss appeared to be associated with the localization of these bacterial clusters at the biofilm-enamel interface. Similar 3D architecture was observed in plaque-biofilms formed in vivo in the presence of sucrose. The formation of complex 3D architectures creates spatially heterogeneous acidic microenvironments in close proximity of enamel surface, which might correlate with the localized pattern of the onset of carious lesions (white spot like) on teeth.

Recently, it was reported that the role of mitochondria-reactive oxygen species (ROS) generating pathway in cisplatin-induced apoptosis is remarkable. Since a variety of molecules are involved in the pathway, a comprehensive approach to delineate the biological interactions of the molecules is required. However, quantitative modeling of the mitochondria-ROS generating pathway based on experiment and systemic analysis using the model have not been attempted so far. Thus, we conducted experiments to measure the concentration changes of critical molecules associated with mitochondrial apoptosis in both human mesothelioma H2052 and their ρ0 cells lacking mitochondrial DNA (mtDNA). Based on the experiments, a novel mathematical model that can represent the essential dynamics of the mitochondrial apoptotic pathway induced by cisplatin was developed. The kinetic parameter values of the mathematical model were estimated from the experimental data. Then, we have investigated the dynamical properties of this model and predicted the apoptosis levels for various concentrations of cisplatin beyond the range of experiments. From parametric perturbation analysis, we further found that apoptosis will reach its saturation level beyond a certain critical cisplatin concentration.
Apoptosis* ; Cisplatin* ; DNA, Mitochondrial ; Humans ; Mesothelioma ; Models, Theoretical ; Oxygen ; Systems Analysis*

Background: Open gastrectomy causes severe postoperative pain. Therefore, we investigated the opioid-sparing effect of the ultrasound-guided bilateral erector spinae plane block (ESPB) after open gastrectomy. Methods: Adult patients undergoing open gastrectomy were randomly assigned to either the ESPB group (ESPB + fentanyl based intravenous patient-controlled analgesia [IV-PCA]) or a control group (fentanyl based IV-PCA only). The primary outcome was total fentanyl equivalent consumption during the first 24 hour postoperatively.Secondary outcomes were pain intensities using a numeric rating scale at the postanesthesia care unit (PACU) and at 3, 6, 12, and 24 hour postoperatively, and the amount of fentanyl equivalent consumption during the PACU stay and at 3, 6, and 12 hour postoperatively, and the time to the first request for rescue analgesia. Results: Fifty-eight patients were included in the analysis. There was no significant difference in total fentanyl equivalent consumption during the first 24 hour postoperatively between the two groups (P = 0.471). Pain intensities were not significantly different between the groups except during the PACU stay and 3 hour postoperatively (P < 0.001, for both). Time to the first rescue analgesia in the ward was longer in the ESPB group than the control group (P = 0.045). Conclusions Ultrasound-guided ESPB did not decrease total fentanyl equivalent consumption during the first 24 hour after open gastrectomy. It only reduced postoperative pain intensity until 3 hour postoperatively compared with the control group. Ultrasound-guided single-shot ESPB cannot provide an efficient opioid-sparing effect after open gastrectomy.

Background: An epidural blood patch (EBP) is a procedure to treat intracranial hypotension that does not respond to conservative treatment. EBPs are commonly repeated when the symptoms persist. In this study, we used a large single-center retrospective cohort and evaluated the factors associated with repeated EBPs. Methods: From January 2010 to December 2020, a total of 596 patients were treated with EBPs for intracranial hypotension. We evaluated the factors associated with repeated EBPs in the entire population, in patients with spontaneous intracranial hypotension (SIH), and in those with available myelographies. Results: In a total of 596 patients, 125 (21.1%) patients required repeated EBPs, and 96/278 (34.5%) in SIH and 29/314 (9.2%) in iatrogenic population. In patients with SIH, international normalized ratio (INR) and cerebrospinal fluid (CSF) leakage on myelographies consistently exhibited significant associations (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.02–1.87; P = 0.043 and OR, 2.18; 95% CI, 1.28–3.69; P = 0.004). In patients with iatrogenic injury, INR and CSF leakage on myelogram did not show difference in repeated EBPs. Conclusions Repeated EBPs may be more frequently required in patients with SIH.Prolonged INR and CSF leakage were associated with repeated EBPs in patient with SIH. Further studies are needed to determine factors associated with repeated EBP requirements.