Estimating dim light melatonin onset time in children using delta changes in melatonin.

We aimed to establish a method for estimating dim light melatonin onset (DLMO) using mathematical slopes calculated from melatonin concentrations at three sampling points before and after sleep in children. The saliva of 30 children (mean age ± SD: 10.2 ± 1.3 years old) was collected under dim-light conditions up to six times every hour starting at 17:30 (t17), namely, 18:30 (t18), 19:30 (t19), 20:30 (t20), 21:30 (t21), 22:30 (t22), and 23:30 (t23), in the evening, and at 6:00 (t30) the following morning. We calculated SLOPEon (mathematical slope between melatonin concentrations at t18 and t20, t21 or t22), SLOPEoff (the slope between t20, t21 or t22, and t30), and ΔSLOPE, which is generated by subtracting SLOPEon from SLOPEoff. DLMO was estimated by multiple regression analysis with the leave-one-out cross-validation (LOOCV) method using SLOPEon and SLOPEoff, and ΔSLOPE. The intraclass correlation coefficient (ICC) between the estimated and measured DLMOs was used as the index of estimation accuracy. DLMOs estimated using multiple regression equations with SLOPEon and SLOPEoff yielded significant ICCs for the measured DLMOs, with the largest ICC at t20 (ICC = 0.634). Additionally, the ICC between the estimated and measured DLMOs using the equation with ΔSLOPE was significant, with a larger ICC at t20 (ICC = 0.726) than that of the equation with SLOPEon and SLOPEoff. Our results showed that DLMO could be estimated with a certain level of accuracy from salivary melatonin levels at three time points before and after sleep in children. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00493-x.

Visualization of latent fingerprints using fluorescence lifetime imaging on paper emitting strong fluorescence.

Latent fingerprints were successfully visualized using fluorescence lifetime imaging (FLIM) on paper which emits strong fluorescence with a lifetime close to that of fingerprints and thus from which it is difficult for time-resolved spectroscopy to visualize fingerprints. Latent fingerprint samples on paper were excited using a 450 nm or 532 nm nanosecond pulsed-laser, and time-resolved fluorescence images were obtained at a delay time of 6-16 ns in intervals of 1 ns, to the excitation pulse. The excitation beam was expanded using a lens, and the fluorescence from the fingerprints was captured using an intensified CCD camera. Because of the large fluorescence intensity of the background paper of approximately two to four orders of magnitude larger than that of the fingerprint, the fingerprint was not visualized on each fluorescence image by time-resolved spectroscopy. However, the fingerprint was visualized in a FLIM image constructed using a series of the fluorescence images for the case with the fluorescence intensity of the background paper being four orders of magnitude larger than that of the fingerprint. The difference in fluorescence lifetime in the FLIM image of the visualized fingerprint and background paper was in the order of 0.1 ns, which was an order of magnitude smaller than the inherent fluorescence lifetime of a few nanoseconds for the fingerprints and paper. It was demonstrated that, at a background fluorescence intensity with a certain order of magnitude larger than that of fingerprints, FLIM has the potential to visualize latent fingerprints which cannot be visualized by time-resolved spectroscopy.

Accelerometer-Measured Physical Activity and Sedentary Time among Children in Japan before and during COVID-19: A Cross-Sectional and Longitudinal Analysis.

This study examined changes in physical activity (PA), sedentary behavior (SB), screen time, sleep, and executive function among Japanese preschoolers between COVID-19 pre-pandemic and pandemic periods, using cross-sectional and longitudinal data. Accelerometer data from 63 children aged 5-6 years were collected from three kindergartens in Tokyo, Japan, in late 2019 (pre-COVID-19). This was compared to the data of 49 children aged 5-6 years from the same kindergartens, collected in late 2020 (during COVID-19). Sixteen children in the pre-COVID-19 cohort also participated in the 2020 survey and provided data for the longitudinal analysis. The mean minutes of PA, SB, screen time, and sleep duration, as well as executive function, were compared between the pre- and during COVID-19 cohorts. After adjusting for school, sex, and accelerometer wear time, there were no significant differences in any of the measured outcomes between the two cohorts. However, the analysis of longitudinal data revealed significant increases in time spent in SB and on screens, and a decrease in light-intensity PA and sleep duration during the pandemic compared to the pre-pandemic period. Results suggest that, despite the COVID-19 pandemic, young children's activity levels and SB did not significantly differ from pre-pandemic levels. However, school-aged children's SB, light PA, and sleep time were affected, although this cannot be disentangled from the effects of the transition to school.

Path-Planning System for Radioisotope Identification Devices Using 4π Gamma Imaging Based on Random Forest Analysis.

We developed a path-planning system for radiation source identification devices using 4π gamma imaging. The estimated source location and activity were calculated by an integrated simulation model by using 4π gamma images at multiple measurement positions. Using these calculated values, a prediction model to estimate the probability of identification at the next measurement position was created by via random forest analysis. The path-planning system based on the prediction model was verified by integrated simulation and experiment for a 137Cs point source. The results showed that 137Cs point sources were identified using the few measurement positions suggested by the path-planning system.

The Pathways Linking to Sleep Habits among Children and Adolescents: A Complete Survey at Setagaya-ku, Tokyo.

It has been noted that Japanese children sleep the least in the world, and this has become a major social issue. This study examined the pathways linked to sleep habits (SH) among children and adolescents. A questionnaire-based survey was conducted in March 2019 on children and their parents at all 63 public elementary and 29 public junior high schools in Setagaya-ku, Tokyo. For the analysis, 22,385 pairs of children-parent responses (valid response rate: 68.8%) with no missing data were used. This survey collected data on SH, physical activity (PA), screen time (ST) for the child, and lifestyle and neighborhood social capital (NSC) for the parents. Moreover, the pathways linking 'NSC' → 'parental lifestyle' → 'child's PA/ST' →'child's SH' were examined through structural equation modeling. The results indicated that children's SH were affected by their PA and ST and influenced by the lifestyle of their parents and the NSC that surrounds them. Thus, we concluded that it is necessary to provide direct interventions and take additional measures with regard to parent lifestyle and their NSC to solve persistent sleep problems in children.

Different Types of Screen Behavior and Depression in Children and Adolescents.

The purpose of this study was to examine the associations between different types of screen behavior and depression, taking into account exercise and sleep among children and adolescents. A total of 23,573 Japanese children and adolescents (aged 8-15 years) participated in this cross-sectional study. Different types of screen behavior, weekly exercise time, sleep duration, and prevalence of depression were assessed using a questionnaire. Independent associations between various types of screen behavior and prevalence of depression were examined using logistic regression analyses after adjusting for age, school, sleep duration, exercise time, and other screen behavior types. A two-way analysis of covariance was conducted to examine whether exercise and sleep can attenuate the negative effects of screen behavior. The associations between screen behavior and depression varied by screen behavior types and participant characteristics. More time spent engaging in newer types of screen behavior, including social media, online games, and online videos, was associated with a higher prevalence of depression. In contrast, more time spent on TV was associated with a lower prevalence of depression. Sufficient exercise can lower the prevalence of depression, regardless of the length of time and content of the screen, and its associations were particularly significant for junior high school girls. Sleep was not associated with the prevalence of depression among any participant group except elementary school boys. Our findings suggest that age- and sex-specific intervention strategies that also consider screen-based behavior can effectively lower the risk of depression in children and adolescents.

Diurnal repeated exercise promotes slow-wave activity and fast-sigma power during sleep with increase in body temperature: a human crossover trial.

The effects of exercise on sleep have been explored from various perspectives, but little is known about how the effects of acute exercise on sleep are produced through physiological functions. We used a protocol of multiple daytime sessions of moderate-intensity aerobic exercise and examined the subsequent effects on sleep structure, core body temperature (CBT), distal-proximal skin temperature gradient (DPG), and subjective parameters. Fourteen healthy men who did not exercise regularly were evaluated under the baseline (no exercise) and exercise conditions on a within-subject crossover basis. Under the exercise condition, each participant performed a 40-min aerobic workout at 40% of maximal oxygen intake, four times between morning and early evening. We observed a 33% increase in slow-wave sleep (SWS; P = 0.005), as well as increases in slow-wave activity (SWA; P = 0.026), the fast-sigma power/SWA ratio (P = 0.005), and subjective sleep depth and restorativeness the following morning. Moreover, both CBT and the DPG increased during sleep after exercise (P = 0.021 and P = 0.047, respectively). Regression analysis identified an increased nocturnal DPG during sleep after exercise as a factor in the increase in SWA. The fast-sigma/SWA ratio correlated with CBT. The performance of acute exercise promotes SWS with nocturnal elevation in the DPG. Both CBT and fast-sigma power may play a role in the specific physiological status of the body after exercise. NEW & NOTEWORTHY We used multiple daytime sessions of moderate-intensity aerobic exercise to examine the effects on the sleep structure, core body temperature (CBT), distal-proximal skin temperature gradient (DPG), and subjective parameters. Significant increases in slow-wave activity (SWA), CBT, DPG, fast-sigma power, and subjective parameters were observed during the night and the following morning. Nocturnal DPG is a factor in the increased SWA.

Current situation and challenges regarding biosimilars in Japan: an example of trastuzumab biosimilars for breast cancer.

Biologics have dramatically changed breast cancer treatment, and trastuzumab has been an essential treatment drug for HER2-positive breast cancer. The introduction of trastuzumab biosimilar offers the potential to deliver long-term cost savings plus efficiencies for healthcare systems in Japan. The goal of biosimilar development is to demonstrate comparability to the original biologic with a different development concept from that of the original biologic. Hence, a better understanding of the biosimilar itself is urgently needed for appropriate adoption and the integration of trastuzumab biosimilars into oncology clinical practice by all stakeholders. This article focuses on the current situation of biosimilars and future perspectives in Japan by using the trastuzumab biosimilar as an example.

Apixaban for the Treatment of Japanese Subjects With Acute Venous Thromboembolism (AMPLIFY-J Study).

BACKGROUND: Anticoagulation is recommended as standard of care for venous thromboembolism (VTE) (pulmonary embolism [PE]/deep vein thrombosis [DVT]), for which unfractionated heparin (UFH) and warfarin are used in Japan. In the multi-regional AMPLIFY study, a fixed-dose regimen of apixaban alone was non-inferior to conventional therapy for treatment of PE/DVT and was associated with significantly fewer bleeding events. METHODS AND RESULTS: Japan phase 3 study (AMPLIFY-J), randomized, active-controlled, open-label study in Japanese subjects with acute PE/DVT, was designed based on AMPLIFY. Key objectives were to investigate safety and efficacy of apixaban in symptomatic PE/DVT subjects during 24-week treatment. UFH/warfarin was used as control treatment. Apixaban was initiated at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 23 weeks. All endpoints and imaging for thrombotic burden were assessed by an event adjudication committee. Eighty subjects were randomized, 33 subjects (41.3%) were aged <65 years. Proportion of major/clinically relevant non-major bleeding was lower in apixaban (7.5%) compared with well-controlled UFH/warfarin (28.2%; median TTR, 70.4%). [corrected]. Recurrent VTE occurred in no subjects in apixaban and in 1 subject in UFH/warfarin. Thrombotic burden results were similar in both groups. Proportions of subjects with adverse events was generally similar in both groups. CONCLUSIONS: Apixaban was well-tolerated and had a favorable safety profile. No clinically important efficacy difference compared with UFH/warfarin was observed.

IL-10 and IL-27 producing dendritic cells capable of enhancing IL-10 production of T cells are induced in oral tolerance.

Oral tolerance is a key feature of intestinal immunity, generating systemic tolerance to ingested antigens (Ag). Dendritic cells (DC) have been revealed as important immune regulators, however, the precise role of DC in oral tolerance induction remains unclear. We investigated the characteristics of DC in spleen, mesenteric lymph node (MLN), and Peyer's patch (PP) after oral Ag administration in a TCR-transgenic mouse model. DC from PP and MLN of tolerized mice induced IL-10 production but not Foxp3 expression in cocultured T cells. IL-10 production was markedly increased after 5-7-day Ag administration especially in PP DC. On the other hand, IL-27 production was increased after 2-5-day Ag administration. CD11b(+) DC, which increased after ingestion of Ag, prominently expressed IL-10 and IL-27 compared with CD11b(-) DC. These results suggest that IL-10 and IL-27 producing DC are increased by interaction with antigen specific T cells in PP, and these DC act as an inducer of IL-10 producing T cells in oral tolerance.