Acute inhibition of AMPA receptors by perampanel reduces amyloid ß-protein levels by suppressing ß-cleavage of APP in Alzheimer's disease models.

Hippocampal hyperexcitability is a promising therapeutic target to prevent Aß deposition in AD since enhanced neuronal activity promotes presynaptic Aß production and release. This article highlights the potential application of perampanel (PER), an AMPA receptor (AMPAR) antagonist approved for partial seizures, as a therapeutic agent for AD. Using transgenic AD mice combined with in vivo brain microdialysis and primary neurons under oligomeric Aß-evoked neuronal hyperexcitability, the acute effects of PER on Aß metabolism were investigated. A single oral administration of PER rapidly decreased ISF Aß40 and Aß42 levels in the hippocampus of J20, APP transgenic mice, without affecting the Aß40 /Aß42 ratio; 5 mg/kg PER resulted in declines of 20% and 31%, respectively. Moreover, PER-treated J20 manifested a marked decrease in hippocampal APP ßCTF levels with increased FL-APP levels. Consistently, acute treatment of PER reduced sAPPß levels, a direct byproduct of ß-cleavage of APP, released to the medium in primary neuronal cultures under oligomeric Aß-induced neuronal hyperexcitability. To further evaluate the effect of PER on ISF Aß clearance, a γ-secretase inhibitor was administered to J20 1 h after PER treatment. PER did not influence the elimination of ISF Aß, indicating that the acute effect of PER is predominantly on Aß production. In conclusion, acute treatment of PER reduces Aß production by suppressing ß-cleavage of amyloid-ß precursor protein effectively, indicating a potential effect of PER against Aß pathology in AD.

Comparison of dynamic tumor tracking error measurement methods for robotic radiosurgery.

BACKGROUND: Dynamic tumor motion tracking is used in robotic radiosurgery for targets subject to respiratory motion, such as lung and liver cancers. Different methods of measuring tracking error have been reported, but the differences among these methods have not been studied, and the optimal method is unknown. PURPOSE: The purpose of this study was to assess and compare tracking errors encountered with individual patients using different evaluation methods for method optimization. METHODS: We compared the beam's eye view (BEV), machine learning (ML), log (addition error: AE), and log (root sum square: RSS) methods. Log (AE) and log (RSS) were calculated from log files. These tracking errors were compared, and the optimal evaluation method was ascertained. A t-test was performed to evaluate statistically significant differences. Here, the significance level was set at 5%. RESULTS: The mean values of BEV, log (AE), log (RSS), and ML were 2.87, 3.91, 2.91, and 3.74 mm, respectively. The log (AE) and ML were higher than BEV (p < 0.001), and log (RSS) was equivalent to the BEV, suggesting that the log (RSS) calculated with the log file method can substitute for the BEV calculated with the BEV method. As RSS error calculation is simpler than BEV calculation, using it may improve clinical practice throughput. CONCLUSION: This study clarified differences among three tracking error evaluation methods for dynamic tumor tracking radiotherapy using a robotic radiosurgery system. The log (RSS) calculated by the log file method was found to be the best alternative to BEV method, as it can calculate tracking errors more easily than the BEV method.

[Evaluation of the Effect of Adiabatic Pulse and B1 Shim to the Radio Frequency Homogeneity in Chemical Shift Imaging].

It is considered that the enhancement of chemical shift and the elevation of signal-to-noise ratio (SNR) induced by high magnetic fields are useful for the evaluation of metabolism using magnetic resonance spectroscopy (MRS). However, the reduction of the localization in MRS seems to be caused by the decreased homogeneity of radio frequency (RF) pulses, especially in chemical shift imaging (CSI). To search the influence of B1 shim mode and the significance of adiabatic pulses, we have examined the changes of RF homogeneity using 3 T magnetic resonance imaging (MRI) with the water phantom and the metabolites phantom (containing acetate and lactate) in CSI. The RF homogeneity and chemical shift artifact were obviously improved using the adiabatic pulses. Improvement of the homogeneity of RF pulses was observed when B1 shim was used. These results suggest the usefulness of CSI using adiabatic pulses and B1 shim when small amount of metabolites of target is measured in MRS.

Development of system using beam's eye view images to measure respiratory motion tracking errors in image-guided robotic radiosurgery system.

The accuracy of the CyberKnife Synchrony Respiratory Tracking System (SRTS) is considered to be patient-dependent because the SRTS relies on an individual correlation between the internal tumor position (ITP) and the external marker position (EMP), as well as a prediction method to compensate for the delay incurred to adjust the position of the linear accelerator (linac). We aimed to develop a system for obtaining pretreatment statistical measurements of the SRTS tracking error by using beam's eye view (BEV) images, to enable the prediction of the patient-specific accuracy. The respiratory motion data for the ITP and the EMP were derived from cine MR images obtained from 23 patients. The dynamic motion phantom was used to reproduce both the ITP and EMP motions. The CyberKnife was subsequently operated with the SRTS, with a CCD camera mounted on the head of the linac. BEV images from the CCD camera were recorded during the tracking of a ball target by the linac. The tracking error was measured at 15 Hz using in-house software. To assess the precision of the position detection using an MR image, the positions of test tubes (determined from MR images) were compared with their actual positions. To assess the precision of the position detection of the ball, ball positions measured from BEV images were compared with values measured using a Vernier caliper. The SRTS accuracy was evaluated by determining the tracking error that could be identified with a probability of more than 95% (Ep95). The detection precision of the tumor position (determined from cine MR images) was < 0.2 mm. The detection precision of the tracking error when using the BEV images was < 0.2mm. These two detection precisions were derived from our measurement system and were not obtained from the SRTS. The median of Ep95 was found to be 1.5 (range, 1.0-3.5) mm. The difference between the minimum and maximum Ep95 was 2.5mm, indicating that this provides a better means of evaluating patient-specific SRTS accuracy. A suitable margin, based on the predicted patient-specific SRTS accuracy, can be added to the clinical target volume.

Comparison of 2005 and 2021 American Thoracic Society/ European Respiratory Society Criteria for Bronchodilator Response.

Cite this article as: Okawa K, Shirai T, Akamatsu T, Hirai K. Comparison of 2005 and 2021 American Thoracic Society/European Respiratory Society criteria for bronchodilator response. Thorac Res Pract. 2024;25(4):168-170.

The liver-to-spleen ratio is a risk factor predicting oxygen demand in COVID-19 patients.

Background: We aimed to investigate risk factors predicting oxygen demand in COVID-19 patients. Methods: Patients admitted to Shizuoka General Hospital with COVID-19 from August 2020 to August 2021 were included. First, we divided patients into groups with and without oxygen demand. Then, we compared patients' clinical characteristics and laboratory and radiological findings to determine factors predicting oxygen demand. Results: One hundred seventy patients with COVID-19 (aged 58±15 years, 57 females) were enrolled. Common comorbidities were cardiovascular diseases (47.6%), diabetes mellitus (28.8%), and dyslipidemia (26.5%). Elder age, higher body mass index, cardiovascular diseases, diabetes mellitus, lower lymphocyte count, albumin, hepatic attenuation value, and the liver-to-spleen ratio (L/S), higher D-dimer, aspartate aminotransferase, lactate dehydrogenase, troponin-T, C-reactive protein, KL-6, chest and abdominal circumference, and visceral fat were found in patients with oxygen demand. According to the multivariate logistic regression analysis, L/S, lymphocyte count, D-dimer, and abdominal circumference under the diaphragm were independent risk factors predicting oxygen demand in COVID-19 patients. Conclusions: On admission, L/S, lymphocyte count, D-dimer, and abdominal circumference were predictive factors for oxygen demand. These factors may help in the appropriate triage of COVID-19 patients in the decision to admit them to the hospital.

Development of a tracking error prediction system for the CyberKnife Synchrony Respiratory Tracking System with use of support vector regression.

PURPOSE: The accuracy of the CyberKnife Synchrony Respiratory Tracking System is dependent on the breathing pattern of a patient. Therefore, the tracking error in each patient must be determined. Support vector regression (SVR) can be used to easily identify the tracking error in each patient. This study aimed to develop a system with SVR that can predict tracking error according to a patient's respiratory waveform. METHODS: Datasets of the respiratory waveforms of 93 patients were obtained. The feature variables were variation in respiration amplitude, tumor velocity, and phase shift between tumor and the chest wall, and the target variable was tracking error. A learning model was evaluated with tenfold cross-validation. We documented the difference between the predicted and actual tracking errors and assessed the correlation coefficient and coefficient of determination. RESULTS: The average difference and maximum difference between the actual and predicted tracking errors were 0.57 ± 0.63 mm and 2.1 mm, respectively. The correlation coefficient and coefficient of determination were 0.86 and 0.74, respectively. CONCLUSION: We developed a system for obtaining tracking error by using SVR. The accuracy of such a system is clinically useful. Moreover, the system can easily evaluate tracking error. We developed a system that can be used to predict the tracking error of SRTS in the CyberKnife Robotic Radiosurgery System using machine learning. The feature variables were the breathing parameters, and the target variable was the tracking error. We used support vector regression algorithm.

Factors affecting the accuracy of respiratory tracking of the image-guided robotic radiosurgery system.

PURPOSE: To analyze the factors affecting the tracking accuracy of the CyberKnife Synchrony Respiratory Tracking System (SRTS). MATERIALS AND METHODS: A dynamic motion phantom (motion phantom) reproduced the respiratory motions of each patient treated with the SRTS using a ball as the target. CyberKnife tracked the ball using the SRTS, and this process was recorded by a video camera mounted on the linear accelerator head. The tracking error was evaluated from the images captured by the video camera. Multiple regression analysis was used to identify factors affecting tracking accuracy from 91 cases. RESULTS: The median tracking error was 1.9 mm (range 0.9-5.3 mm). Four factors affected the tracking accuracy: the average absolute amplitude of the tumor motion in the cranio-caudal (CC) direction (p = 0.007), average position gap due to the phase shift between the internal tumor and external marker positions in the CC direction (p < 0.001), and average velocity of the tumor in the CC (p < 0.001) and anterior-posterior directions (p = 0.033). CONCLUSION: We identified factors that affected tracking accuracy. This information may assist the identification of suitable margins that should be added to each patient's clinical target volume.

Recovery from acute pediatric complex regional pain syndrome type I after ankle sprain by early pharmacological and physical therapies in primary care: a case report.

BACKGROUND: Complex regional pain syndrome type I (CRPS I) in children is a serious condition disrupting the family and school life of patients with the condition after it fully develops. It has been emphasized that early diagnosis is closely associated with earlier reduction of pain leading to preferable outcomes. OBJECTIVES: To report a case of acute CRPS I in a boy who was found to develop this condition by a routine visual analog scale (VAS) pain monitoring and who recovered from CRPS I at an early phase by prompt pharmacological, physical, and educational therapies. STUDY DESIGN: Case report. CASE REPORT: A 12-year-old boy sprained his left ankle while playing soccer and was referred to our clinic 4 days after the injury. At the first visit, he could walk, reporting motion pain with a VAS scale of 80 mm. On day 5, pain intensity increased to 100 mm, and a diagnosis of acute CRPS I was made. On day 7, he could not move the injured ankle; therefore celecoxib and pregabalin were administered, and physical and educational therapies started. On day 35, pain intensity was 0 mm and he could walk and run normally. CONCLUSION: Routine monitoring of VAS for every patient in pain is useful to discover an abnormal transition of VAS, enabling the early diagnosis of CRPS I. Inflammation and peripheral or central sensitization are postulated for early development of CRPS I. The present case suggested a combination of physical therapy and pharmacological intervention with celecoxib and pregabalin reduced peripheral and central sensitization.

Evaluation of Dose Uncertainty to the Target Associated With Real-Time Tracking Intensity-Modulated Radiation Therapy Using the CyberKnife Synchrony System.

We investigated the dose uncertainty caused by errors in real-time tracking intensity-modulated radiation therapy (IMRT) using the CyberKnife Synchrony Respiratory Tracking System (SRTS). Twenty lung tumors that had been treated with non-IMRT real-time tracking using CyberKnife SRTS were used for this study. After validating the tracking error in each case, we did 40 IMRT planning using 8 different collimator sizes for the 20 patients. The collimator size was determined for each planning target volume (PTV); smaller ones were one-half, and larger ones three-quarters, of the PTV diameter. The planned dose was 45 Gy in 4 fractions prescribed at 95% volume border of the PTV. Thereafter, the tracking error in each case was substituted into calculation software developed in house and randomly added in the setting of each beam. The IMRT planning incorporating tracking errors was simulated 1000 times, and various dose data on the clinical target volume (CTV) were compared with the original data. The same simulation was carried out by changing the fraction number from 1 to 6 in each IMRT plan. Finally, a total of 240 000 plans were analyzed. With 4 fractions, the change in the CTV maximum and minimum doses was within 3.0% (median) for each collimator. The change in D99 and D95 was within 2.0%. With decreases in the fraction number, the CTV coverage rate and the minimum dose decreased and varied greatly. The accuracy of real-time tracking IMRT delivered in 4 fractions using CyberKnife SRTS was considered to be clinically acceptable.

Effect of residual patient motion on dose distribution during image-guided robotic radiosurgery for skull tracking based on log file analysis.

PURPOSE: The present study aimed to assess the effect of residual patient motion on dose distribution during intracranial image-guided robotic radiosurgery by analyzing the system log files. MATERIALS AND METHODS: The dosimetric effect was analyzed according to the difference between the original and estimated dose distributions, including targeting error, caused by residual patient motion between two successive image acquisitions. One hundred twenty-eight treatments were analyzed. Forty-two patients were treated using the isocentric plan, and 86 patients were treated using the conformal (non-isocentric) plan. RESULTS: The median distance from the imaging center to the target was 55 mm, and the median interval between the acquisitions of sequential images was 79 s. The median translational residual patient motion was 0.1 mm for each axis, and the rotational residual patient motion was 0.1° for Δpitch and Δroll and 0.2° for Δyaw. The dose error for D 95 was within 1 % in more than 95 % of cases. The maximum dose error for D 10 to D 90 was within 2 %. None of the studied parameters, including the interval between the acquisitions of sequential images, was significantly related to the dosimetric effect. CONCLUSION: The effect of residual patient motion on dose distribution was minimal.