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Takayuki Kunisawa,1 Hidefumi Kasai,2 Makoto Suda,2 Manabu Yoshimura,3 Ami Sugawara,3 Yuki Izumi,3 Takafumi Iida,3 Atsushi Kurosawa,3 Hiroshi Iwasaki3 1Surgical Operation Department, Asahikawa Medical University Hospital, Hokkaido, Japan; 2Clinical Study Management Division, Bell Medical Solutions Inc, Tokyo, Japan; 3Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan Background: Olprinone decreases the cardiac preload and/or afterload because of its vasodilatory effect and increases myocardial contractility by inhibiting phosphodiesterase III. Purpose: The objective of this study was to characterize the population pharmacokinetics of olprinone after a single continuous infusion in healthy male volunteers. Methods: We used 500 plasma concentration data points collected from nine healthy male volunteers for the study. The population pharmacokinetic analysis was performed using the nonlinear mixed effect model (NONMEM®) software. Results: The time course of plasma concentration of olprinone was best described using a two-compartment model. The final pharmacokinetic parameters were total clearance (7.37 mL/minute/kg), distribution volume of the central compartment (134 mL/kg), intercompartmental clearance (7.75 mL/minute/kg), and distribution volume of the peripheral compartment (275 mL/kg). The interindividual variability in the total clearance was 12.4%, and the residual error variability (exponential and additive) were 22.2% and 0.129 (standard deviation). The final pharmacokinetic model was assessed using a bootstrap method and visual predictive check. Conclusion: We developed a population pharmacokinetic model of olprinone in healthy male adults. The bootstrap method and visual predictive check showed that this model was appropriate. Our results might be used to develop the population pharmacokinetic model in patients. Keywords: phosphodiesterase III inhibitor, men, pharmacokinetic model

A new remote nondestructive inspection technique, based on thermoelastic temperature measurement by infrared thermography, is developed for detection and evaluation of fatigue cracks propagating from welded joints in steel bridges. Fatigue cracks are detected from localized high thermoelastic temperature change at crack tips due to stress singularity under variable loading from traffics on the bridge. Selfreference lock-in data processing technique is developed for the improvement of signal/noise ratio in the crack detection process. The technique makes it possible to perform correlation processing without an external reference signal. It is very difficult to detect through-deck type fatigue cracks in steel decks by the conventional NDT technique, since they are not open to the inspection. In this paper, self-reference lock-in thermography is applied for detection of through-deck type fatigue cracks. Experiments are carried out to steel deck sample, which simulates an actual steel bridge, during crack propagation test. It is found that significant stress concentration zone can be observed near the crack front, which enabled us to detect through-deck type fatigue cracks and to estimate its size.

Background/purpose: Large language models (LLMs) such as OpenAI's ChatGPT, Google's Bard, and Microsoft's Bing Chat have shown potential as educational tools in the medical and dental fields. This study evaluated their effectiveness using questions from the Japanese national dental hygienist examination, focusing on textual information only. Materials and methods: We analyzed 73 questions from the 32nd Japanese national dental hygienist examination, conducted in March 2023, using LLMs ChatGPT-3.5, GPT-4, Bard, and Bing Chat. Each question was categorized into one of nine domains. Standardized prompts were used for all LLMs, and Fisher's exact test was applied for statistical analysis. Results: GPT-4 achieved the highest accuracy (75.3%), followed by Bing (68.5%), Bard (66.7%), and GPT-3.5 (63.0%). There were no statistically significant differences between the LLMs. The performance varied across different question categories, with all models excelling in the ‘Disease mechanism and promotion of recovery process' category (100% accuracy). GPT-4 generally outperformed other models, especially in multi-answer questions. Conclusion: GPT-4 demonstrated the highest overall accuracy among the LLMs tested, indicating its superior potential as an educational support tool in dental hygiene studies. The study highlights the varied performance of different LLMs across various question categories. While GPT-4 is currently the most effective, the capabilities of LLMs in educational settings are subject to continual change and improvement.

Introduction Transplant renal vein thrombosis is a serious post‐transplant complication. We report a case in which a thrombus was found in the transplant renal vein and rescued the transplanted kidney utilizing interventional radiology. Case presentation A 56‐year‐old woman underwent ABO‐compatible living donor renal transplantation due to impaired renal function caused by IgA nephropathy. On postoperative Day 13, there was a finding on transplant renal echocardiography that appeared to be an interruption of peripheral renal blood flow in diastole. Contrast‐enhanced computed tomography revealed that the vein was occluded due to the hematoma, and thrombosis was observed within, and distal contrast showed regurgitation into the collateral vessels. The stenosis was breached and balloon dilation restored progressive blood flow through interventional radiology. Conclusion Although open surgical thrombectomy is mainly considered for treatment for transplant renal vein thrombosis, interventional radiology might be the alternative treatment option.

Abstract Determining the content of the nutrient choline in foods and obtaining the required amount from the diet are crucial. One way to measure choline in foods is by converting choline esters to free choline via acid hydrolysis, followed by quantifying the total choline, as adopted by the AOAC method (AOAC-Choline); however, certain choline esters are difficult to hydrolyse. Here, we investigated various acid hydrolysis conditions to establish a reliable method for determining the total choline in foods by detecting free choline using highly sensitive and selective mass spectrometry. Hydrolysis in 0.055 mol/L HCl for 8 h in an autoclave (121 °C) was found to be optimal for the hydrolysis of choline esters in various foods. Twenty-four foods, including grains, seed, vegetables, fruits, mushroom, algae, fish, meats, beverage, processed foods, and egg, were measured. The trends in the total choline content were consistent with previous reports; however, the choline content was 10–20% higher than that measured using AOAC-Choline. Therefore, re-evaluation of the total choline content in foods using our constructed method is recommended. This reassessment will allow for a more reliable determination of choline intake for maintaining health.

Background/purpose: Rapid advancements in AI technology have led to significant interest in its application across various fields, including medicine and dentistry. This study aimed to assess the capabilities of ChatGPT-4V with image recognition in answering image-based questions from the Japanese National Dental Examination (JNDE) to explore its potential as an educational support tool for dental students. Materials and methods: The dataset used questions from the JNDE, which was conducted in January 2023, with a focus on image-related queries. ChatGPT-4V was utilized, and standardized prompts, question texts, and images were input. Data and statistical analyses were conducted using Qlik Sense® and GraphPad Prism. Results: The overall correct response rate of ChatGPT-4V for image-based JNDE questions was 35.0 %. The correct response rates were 57.1 % for compulsory questions, 43.6 % for general questions, and 28.6 % for clinical practical questions. In specialties like Dental Anesthesiology and Endodontics, ChatGPT-4V achieved correct response rates above 70 %, while response rates for Orthodontics and Oral Surgery were lower. A higher number of images in questions was correlated with lower accuracy, suggesting an impact of the number of images on correct and incorrect responses. Conclusion: While innovative, ChatGPT-4V’s image recognition feature exhibited limitations, especially in handling image-intensive and complex clinical practical questions, and is not yet fully suitable as an educational support tool for dental students at its current stage. Further technological refinement and re-evaluation with a broader dataset are recommended.

An aneurysmal subarachnoid hemorrhage (aSAH) is a devastating event associated with a high mortality and morbidity rate. Though numerous medications are used to prevent cerebral vasospasm and vasospasm-related cerebral infarction after aSAH, no effective pharmacological treatment has been established. Clazosentan, a highly selective endothelin receptor type A antagonist, was approved for use in Japan in April 2022 based on results of two pivotal randomized, placebo-controlled phase 3 studies (JapicCTI-163369, JapicCTI-163368). These studies indicated that clazosentan significantly reduced the incidence of vasospasm-related morbidity and all-cause mortality after aneurysm coiling and clipping. Clazosentan is thus expected to become a “game changer” for improving the neurological prognosis after aSAH. However, other reports indicate that even when clazosentan or nimodipine are administered for prophylaxis against delayed neurological decline, patients treated with increased colloid administration or hypertonic saline (3% sodium chloride) load exhibit poor functional outcome and higher mortality, suggesting that extra fluid and sodium derived from prophylactic colloid administration contribute to negative outcomes after aSAH. Pharmacological treatments such as clazosentan in addition to perioperative management involving delivery of less water and sodium might be crucial for achieving better outcomes than conventional therapy. Based on a literature review, we present here the future perspectives regarding clazosentan and the necessity for modifying management of the water-electrolyte balance by focusing on endothelin-1 and blood–brain barrier disruption.

ABSTRACT Non-tuberculosis mycobacteria (NTM), particularly Mycobacterium abscessus subsp. abscessus (M. abscessus), are increasingly being recognized as etiological agents of NTM pulmonary disease. However, treatment options for M. abscessus are limited owing to their natural resistance to most antibiotics, including β-lactams. M. abscessus produces a class A β-lactamase, whose activity is inhibited by cyclic boronic acid β-lactamase inhibitors. We aimed to evaluate the in vitro effects of xeruborbactam, a cyclic boronic acid β-lactamase inhibitor, against M. abscessus when combined with five β-lactams (amoxicillin, tebipenem, cefdinir, cefuroxime, and cefoxitin). The drug susceptibilities of 43 M. abscessus clinical isolates obtained from 43 patients between August 2005 and May 2014 were tested. The MIC results for each β-lactam with or without 4 µg/mL xeruborbactam were examined. Xeruborbactam lowered the MIC90 values of tebipenem, amoxicillin, cefuroxime, and cefdinir by 5, ≥4, 3, and 3 dilutions, respectively. The MIC90 values of cefoxitin without xeruborbactam were 32 µg/mL and did not change upon the addition of xeruborbactam. The lowest MIC90 value was obtained for tebipenem with xeruborbactam. Almost all isolates had an MIC of 4 µg/mL; one isolate had an MIC of 2 µg/mL. With respect to the susceptibility to the same family drug, the number of susceptible isolates increased from 1/43 (2%) to 43/43 (100%) for tebipenem with xeruborbactam. Combining tebipenem and xeruborbactam could be considered an effective all-oral regimen that benefits outpatient treatment of M. abscessus pulmonary disease.IMPORTANCEMycobacterium abscessus subsp. abscessus (M. abscessus) disease is treated in two phases; injectable drugs for initial followed by others for continuation. There is a need to develop all-oral treatment methods for M. abscessus infection, especially in the continuation phase. However, treatment options for M. abscessus are limited owing to their natural resistance to most antibiotics. This is the first report to evaluate the in vitro effects of xeruborbactam, a cyclic boronic acid β-lactamase inhibitor capable of inhibiting the class A β-lactamase produced by M. abscessus, against 43 M. abscessus clinical isolates when combined with five β-lactam antibiotics. Xeruborbactam lowered the MIC90 values of tebipenem by five dilutions, and the number of susceptible isolates increased from 1/43 (2%) to 43/43 (100%). We showed that the tebipenem-xeruborbactam combination might be of interest to explore further as a potentially effective oral regimen for outpatient treatment of M. abscessus pulmonary disease.