微小物体可視化センサLSIの設計

金沢大学大学院自然科学研究科情報システム金沢大学工学

Carcinogen-induced Thyroid Proliferative Lesions in Wistar Hannover GALAS Rats with Thyroid Dysplasia

Incidences and morphological features of thyroid proliferative lesions induced by carcinogens in Wistar Hannover GALAS rats (GALAS rats) showing normal growth with or without thyroid dysplasia were examined. All thyroid tissue samples were obtained from our recently conducted study using male GALAS rats treated with 5 carcinogens according to the medium-term multiorgan carcinogenicity bioassay protocol (called DMBDD treatment). In the DMBDD-treated rats, thyroid dysplasia was found in 9 out of 114 rats. Follicular cell adenomas were found in 5 out of 9 rats with thyroid dysplasia and in 7 out of 105 rats without thyroid dysplasia. The incidence of adenoma was significantly increased in rats with thyroid dysplasia (55.6%) compared with that in rats without thyroid dysplasia (6.7%). Adenomas in rats with thyroid dysplasia were observed as single or multiple nodules, well demarcated and composed of variously sized vacuolated cells or unvacuolated cells. These histopathological features and staining profiles of luminal colloid for PAS and thyroglobulin, together with PCNA-positive cells, were fundamentally similar to those of rats without thyroid dysplasia. On the other hand, the luminal colloid in adenomas of rats with thyroid dysplasia had a tendency to be poorly stained for T4 compared with that of rats without thyroid dysplasia. From these findings, it appears that dysplastic thyroids of rats showing normal growth are more sensitive to carcinogens than normal thyroids. In addition, the morphological features of carcinogen-induced thyroid proliferative lesions in GALAS rats with thyroid dysplasia were fundamentally similar to those of rats without thyroid dysplasia, except for the vacuoles and T4 staining profile

The arousal level of consciousness required for working memory performance: An anaesthesia study

Osaka M., Minamoto T., Ikeda T., et al. The arousal level of consciousness required for working memory performance: An anaesthesia study. European Journal of Neuroscience 59, 3151 (2024); https://doi.org/10.1111/ejn.16383.Regarding the stage of arousal level required for working memory to function properly, limited studies have been conducted on changes in working memory performance when the arousal level of consciousness decreases. This study aimed to experimentally clarify the stages of consciousness necessary for optimal working memory function. In this experiment, the sedation levels were changed step-by-step using anaesthesia, and the performance accuracy during the execution of working memory was assessed using a dual-task paradigm. Participants were required to categorize and remember words in a specific target category. Categorization performance was measured across four different sedative phases: before anaesthesia (baseline), and deep, moderate and light stages of sedation. Short-delay recognition tasks were performed under these four sedative stages, followed by long-delay recognition tasks after participants recovered from sedation. The results of the short-delay recognition task showed that the performance was lowest at the deep stage. The performance of the moderate stage was lower than the baseline. In the long-delay recognition task, the performance under moderate sedation was lower than that under baseline and light sedation. In addition, the performance under light sedation was lower than that under baseline. These results suggest that task performance becomes difficult under half sedation and that transferring information to long-term memory is difficult even under one-quarter sedation

Simultaneous Validation of Seven Physical Activity Questionnaires Used in Japanese Cohorts for Estimating Energy Expenditure: A Doubly Labeled Water Study

Background: Physical activity questionnaires (PAQs) used in large-scale Japanese cohorts have rarely been simultaneously validated against the gold standard doubly labeled water (DLW) method. This study examined the validity of seven PAQs used in Japan for estimating energy expenditure against the DLW method.Methods: Twenty healthy Japanese adults (9 men; mean age, 32.4 [standard deviation {SD}, 9.4] years, mainly researchers and students) participated in this study. Fifteen-day daily total energy expenditure (TEE) and basal metabolic rate (BMR) were measured using the DLW method and a metabolic chamber, respectively. Activity energy expenditure (AEE) was calculated as TEE − BMR − 0.1 × TEE. Seven PAQs were self-administered to estimate TEE and AEE.Results: The mean measured values of TEE and AEE were 2,294 (SD, 318) kcal/day and 721 (SD, 161) kcal/day, respectively. All of the PAQs indicated moderate-to-strong correlations with the DLW method in TEE (rho = 0.57–0.84). Two PAQs (Japan Public Health Center Study [JPHC]-PAQ Short and JPHC-PAQ Long) showed significant equivalence in TEE and moderate intra-class correlation coefficients (ICC). None of the PAQs showed significantly equivalent AEE estimates, with differences ranging from −547 to 77 kcal/day. Correlations and ICCs in AEE were mostly weak or fair (rho = 0.02–0.54, and ICC = 0.00–0.44). Only JPHC-PAQ Short provided significant and fair agreement with the DLW method.Conclusions: TEE estimated by the PAQs showed moderate or strong correlations with the results of DLW. Two PAQs showed equivalent TEE and moderate agreement. None of the PAQs showed equivalent AEE estimation to the gold standard, with weak-to-fair correlations and agreements. Further studies with larger sample sizes are needed to confirm these findings

Moderate sedation induced by general anaesthetics disrupts audio-spatial feature binding with sustained P3 components in healthy humans

Minamoto Takehiro, Ikeda Takashi, Kang Hongling, et al. Moderate sedation induced by general anaesthetics disrupts audio-spatial feature binding with sustained P3 components in healthy humans. Neuroscience of Consciousness 2018, 876 (2018); https://doi.org/10.1093/nc/niy002.Feature binding is considered to be the basis for conscious stimulus perception, while anaesthetics exert a gradient effect on the loss of consciousness (LOC). By integrating these two streams of research, the present study assessed the effect of two anaesthetic agents (i.e. propofol and midazolam) on audio-spatial feature binding. We also recorded the electrophysiological activity of the frontal channels. Using pharmacokinetic simulation, we determined the effect-site concentration (Ce) of the anaesthetics at loss of response to verbal command and eyelash reflex. We subsequently adjusted Ce to 75%, 50% and 25% of Ce-LOC to achieve deep, moderate and light sedation, respectively. Behavioural results showed that moderate sedation selectively disrupted feature binding. The frontal channels showed a P3 component (350–600 ms peristimulus period) following the presentation of audio-spatial stimuli at baseline and under moderate and light sedations. Critically, the late event-related potential component (600–1000 ms) returned to the pre-activated level (0–350 ms) at baseline and under light sedation but was sustained under moderate sedation. We propose that audio-spatial feature binding may require the presence of a P3 component and its subsequent and sufficient decline, as under anaesthetic-induced moderate sedation the P3 component was sustained and featured binding was impaired

Accuracy of 12 Wearable Devices for Estimating Physical Activity Energy Expenditure Using a Metabolic Chamber and the Doubly Labeled Water Method: Validation Study

Background: Self-monitoring using certain types of pedometers and accelerometers has been reported to be effective for promoting and maintaining physical activity (PA). However, the validity of estimating the level of PA or PA energy expenditure (PAEE) for general consumers using wearable devices has not been sufficiently established.Objective: We examined the validity of 12 wearable devices for determining PAEE during 1 standardized day in a metabolic chamber and 15 free-living days using the doubly labeled water (DLW) method.Methods: A total of 19 healthy adults aged 21 to 50 years (9 men and 10 women) participated in this study. They followed a standardized PA protocol in a metabolic chamber for an entire day while simultaneously wearing 12 wearable devices: 5 devices on the waist, 5 on the wrist, and 2 placed in the pocket. In addition, they spent their daily lives wearing 12 wearable devices under free-living conditions while being subjected to the DLW method for 15 days. The PAEE criterion was calculated by subtracting the basal metabolic rate measured by the metabolic chamber and 0.1×total energy expenditure (TEE) from TEE. The TEE was obtained by the metabolic chamber and DLW methods. The PAEE values of wearable devices were also extracted or calculated from each mobile phone app or website. The Dunnett test and Pearson and Spearman correlation coefficients were used to examine the variables estimated by wearable devices.Results: On the standardized day, the PAEE estimated using the metabolic chamber (PAEEcha) was 528.8±149.4 kcal/day. The PAEEs of all devices except the TANITA AM-160 (513.8±135.0 kcal/day; P>.05), SUZUKEN Lifecorder EX (519.3±89.3 kcal/day; P>.05), and Panasonic Actimarker (545.9±141.7 kcal/day; P>.05) were significantly different from the PAEEcha. None of the devices was correlated with PAEEcha according to both Pearson (r=−.13 to .37) and Spearman (ρ=−.25 to .46) correlation tests. During the 15 free-living days, the PAEE estimated by DLW (PAEEdlw) was 728.0±162.7 kcal/day. PAEE values of all devices except the Omron Active style Pro (716.2±159.0 kcal/day; P>.05) and Omron CaloriScan (707.5±172.7 kcal/day; P>.05) were significantly underestimated. Only 2 devices, the Omron Active style Pro (r=.46; P=.045) and Panasonic Actimarker (r=.48; P=.04), had significant positive correlations with PAEEdlw according to Pearson tests. In addition, 3 devices, the TANITA AM-160 (ρ=.50; P=.03), Omron CaloriScan (ρ=.48; P=.04), and Omron Active style Pro (ρ=.48; P=.04), could be ranked in PAEEdlw.Conclusions: Most wearable devices do not provide comparable PAEE estimates when using gold standard methods during 1 standardized day or 15 free-living days. Continuous development and evaluations of these wearable devices are needed for better estimations of PAEE

Potential application of measuring serum infliximab levels in rheumatoid arthritis management: A retrospective study based on KURAMA cohort data

Infliximab (IFX) therapy has considerably improved the treatment of rheumatoid arthritis (RA). However, some patients still do not respond adequately to IFX therapy, or the efficacy of the treatment diminishes over time. Although previous studies have reported a relationship between serum IFX levels and therapeutic efficacy, the potential applications of IFX therapeutic drug monitoring (TDM) in clinical practice remain unclear. The purpose of this study was to investigate the potential applications of IFX TDM by analyzing a Japanese cohort database. Data were collected retrospectively from the Kyoto University Rheumatoid Arthritis Management Alliance cohort between January 1, 2011, and December 31, 2018. Serum IFX levels were measured using a liquid chromatography-tandem mass spectrometer. Out of the 311 RA patients that used IFX, 41 were eligible for the analysis. Serum IFX levels were significantly higher in responders than in non-responders. An optimal cut-off value was determined to be 0.32 μg/mL based on a receiver operating characteristic curve. At the IFX measurement point, a better therapeutic response was observed in the high IFX group (n = 32) than in the low IFX group (n = 9). Conversely, at the maximum effect point, when DAS28-ESR was the lowest between IFX introduction and measurement points, there were no differences in responder proportions between the low and high IFX groups. IFX primary ineffectiveness could be avoided with appropriate dose escalation without blood concentration measurement in clinical practice. In conclusion, IFX TDM could facilitate the identification of secondary non-responders and in turn, proper IFX use