Ictal direct current shifts contribute to defining the core ictal focus in epilepsy surgery

難治てんかん焦点の新しいバイオマーカー「発作時DC電位」 --国内5施設の共同研究での世界初の成果--. 京都大学プレスリリース. 2022-09-05.Identifying the minimal and optimal epileptogenic area to resect and cure is the goal of epilepsy surgery. To achieve this, EEG analysis is recognized as the most direct way to detect epileptogenic lesions from spatiotemporal perspectives. Although ictal direct-current shifts (icDCs; below 1 Hz) and ictal high-frequency oscillations (icHFOs; above 80 Hz) have received increasing attention as good indicators that can add more specific information to the conventionally defined seizure-onset zone, large cohort studies on postoperative outcomes are still lacking. This work aimed to clarify whether this additional information, particularly icDCs which is assumed to reflect extracellular potassium concentration, really improve postoperative outcomes. To assess the usefulness in epilepsy surgery, we collected unique EEG datasets recorded with a longer time constant of 10 sec using an alternate current amplifier. 61 patients [15 with mesial temporal lobe epilepsy and 46 with neocortical epilepsy] who had undergone invasive presurgical evaluation for medically refractory seizures at five institutes in Japan, were retrospectively enrolled in this study. Among intracranially implanted electrodes, the two core electrodes of both icDCs and icHFOs were independently identified by board-certified clinicians based on unified methods. The occurrence patterns, such as their onset time, duration, and amplitude (power) were evaluated to extract the features of both icDCs and icHFOs. Additionally, we examined whether the resection ratio of the core electrodes of icDCs and icHFOs independently correlated with favorable outcomes. A total of 53 patients with 327 seizures were analyzed for wide-band EEG analysis, and 49 patients were analyzed for outcome analysis. icDCs were detected in the seizure-onset zone more frequently than icHFOs among both patients (92% vs. 71%) and seizures (86% vs. 62%). Additionally, icDCs significantly preceded icHFOs in patients exhibiting both biomarkers, and icDCs occurred more frequently in neocortical epilepsy patients than in mesial temporal lobe epilepsy patients. Finally, although a low corresponding rate was observed for icDCs and icHFOs (39%) at the electrode level, complete resection of the core area of icDCs significantly correlated with favorable outcomes, similar to icHFO outcomes. Our results provide a proof of concept that the independent significance of icDCs from icHFOs should be considered as reliable biomarkers to achieve favorable outcomes in epilepsy surgery. Moreover, the different distribution of the core areas of icDCs and icHFOs may provide new insights into the underlying mechanisms of epilepsy, in which not only neurons but also glial cells may be actively involved via extracellular potassium levels

Case report: Young-onset large vessel ischemic stroke due to hyperhomocysteinemia associated with the C677T polymorphism on 5,10-methylenetetrahydrofolate reductase and multi-vitamin deficiency

Hyperhomocysteinemia is an important risk factor for cerebral infarction. Herein, we report on a 30-year-old man previously diagnosed with epilepsy who presented with right hemiplegia and total aphasia. Magnetic resonance imaging showed a fronto-temporal ischemic lesion due to occlusion of the left middle cerebral artery. Clinical testing and imaging demonstrated that he had hyperhomocysteinemia induced by multiple factors including the C677T polymorphism on 5.10-methylenetetrahydrofolate reductase (MTHFR), and multiple vitamin deficiencies. The C677T polymorphism on MTHFR is closely related to hyperhomocysteinemia and folate deficiency in epileptic patients who are taking multiple anti-convulsants. Given hyperhomocysteinemia can independently cause stroke at a young age, physicians should periodically examine plasma homocysteine and serum folic acid levels in epileptic patients who are on long-term regimens of multiple anti-epileptic drugs

A Semi-Analytical Nonlinear Regression Approach for Weld Profile Prediction: A Case of Alternating Current Square Waveform Submerged Arc Welding of Heat Resistant Steel

The complexity in weld profile caused by abrupt change in polarity in square waveform welding is investigated through the development of a model capable to accurately predict weld profile. A semi-analytical model is conceived wherein characteristic attributes of a composite parabolic-elliptic function, which represent the weld profile, are obtained through nonlinear regression (NLR). The proposed model is demonstrated for its efficacy in the prediction of weld profile over a wide range of welding parameters, vis-à-vis, welding current, frequency, electrode negative (EN) ratio, and welding velocity. The investigation suggests that the center and outer cores of welding arc remains more active during positive and negative polarity, respectively, that leads to distinct macroscopic zones in weld cross section and thus, necessitates a composite profile for representation of weld profile. The intersection of the zones forms a metallurgical notch which the investigation offers a method to estimate and thus control. Unlike the convention continuous arc welding, the waveform arc welding caters welding at higher velocity without compromising the weld penetration and almost abolishing the metallurgical notch as well

Construction of HGF-Displaying Yeast by Cell Surface Engineering

Hepatocyte growth factor (HGF) has been investigated as a regulator for immune reactions caused by transplantation and autoimmune diseases and other biological functions. Previous studies demonstrated that cDNA-encoding HGF administration could inhibit acute graft-versus-host disease (GVHD) after treatment via hematopoietic stem cell transplantation. This study aimed to show the preparation of HGF protein on yeast cell surfaces to develop a tool for the oral administration of HGF to a GVHD mouse model. In this study, full-length HGF and the heavy chain of HGF were genetically fused with α-agglutinin and were successfully displayed on the yeast cell surface. This study suggested that yeast cell surface display engineering could provide a novel administration route for HGF

Performance Evaluation of Alternating Current Square Waveform Submerged Arc Welding as a Candidate for Fabrication of Thick Welds in 2.25Cr-1Mo Heat-Resistant Steel

The paper evaluates the performance of alternating current (AC) square waveform submerged arc welding (SAW) as a candidate technology for manufacturing thick welds for high-pressure vessels. A new mathematical formulation for calculating melting efficiency in square waveform arc welding is presented. The melting efficiency and the heat consumption are presented as a mathematical model of welding parameters, namely welding current, welding speed, current frequency, and electrode negativity (EN) ratio. The proposed approach is demonstrated through the welding of 2.25Cr-1Mo heat-resistant steel performed over a wide range of welding parameters. The investigation provides deeper insights into the interplay between process parameter, total heat consumption, and melting efficiency. The effect on flux consumption is also explained. The melting efficiency is inversely proportional to flux consumption. The welding heat does not necessarily promote the plate melting. Improper use of welding heat may lead to decreased melting efficiency and increased unwanted melting and consumption of welding flux. Compared to the conventional direct current (DC) power sources, the AC square waveform welding achieves almost the same order of melting efficiency with added advantages of better weld bead shape and flux consumption in a desirable range. The two additional parameters (frequency and EN ratio) of the AC square waveform power source provide more freedom to fine-tune the process and thereby efficiently use welding heat. The results of this investigation will be advantageous to the designers and fabricators of high-pressure vessels using AC square waveform welding.status: Published onlin