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Sumiko Abe,1 Mina Yasuda,1,2 Kazunori Tobino,1,2 Sonoko Harada,1,3 Hitoshi Sasano,1 Yuki Tanabe,1 Yuuki Sandhu,1 Tomohito Takeshige,1 Kei Matsuno,1 Tetsuhiko Asao,1 Takuto Sueyasu,2 Saori Nishizawa,2 Kohei Yoshimine,2 Yuki Ko,2 Yuki Yoshimatsu,2 Kosuke Tsuruno,2 Hiromi Ide,2 Haruhi Takagi,1 Jun Ito,1 Tetsutaro Nagaoka,1 Norihiro Harada,1,3,4 Kazuhisa Takahashi1,4 1Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan; 2Department of Respiratory Medicine, Iizuka Hospital, Fukuoka, Japan; 3Atopy (Allergy) Research Center, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan; 4Research Institute for Diseases of Old Age, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, JapanCorrespondence: Norihiro Harada, Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo, 113-8431, Japan, Tel +81-3-5802-1063, Fax +81-3-5802-1617, Email nor@juntendo.ac.jpBackground: Bronchial thermoplasty (BT) improves clinical outcomes and quality of life for patients with severe asthma and has shown sustained reductions in airway narrowing and air trapping in previous CT studies. However, there is a lack of a comprehensive analysis, including CT evaluation, of clinical outcomes in Japanese patients who have undergone BT for severe asthma. This study aimed to evaluate the impact of BT in Japanese asthma patients, with a focus on the CT metric “WA at Pi10” to assess airway disease.Methods: Twelve patients with severe persistent asthma who underwent BT were assessed using ACQ6, AQLQ, pulmonary function tests, FeNO measurement, blood sampling, and chest CT before BT and one year after the third procedure for the upper lobes.Results: The median age of the patient was 62.0 years, 7/12 (58.3%) were male, 4/12 (33.3%) used regular oral corticosteroids, and 8/12 (66.7%) received biologics. Median FEV1% was 73.6%, and median peripheral eosinophil count was 163.8/μL. After one year of BT, ACQ6 scores improved from 2.4 to 0.8 points (p = 0.007), and AQLQ scores improved from 4.3 to 5.8 points (p < 0.001). Significant improvements were also observed in asthma exacerbations, unscheduled visits due to exacerbations, FeNO, and √WA at Pi10 (p < 0.05). The baseline mucus score on the CT findings was negatively correlated with FEV1 (r = − 0.688, p = 0.013) and with the maximum mid-expiratory flow rate (r = − 0.631, p = 0.028), and positively correlated with the peripheral blood eosinophil count (r = − 0.719, p = 0.008). Changes in √WA at Pi10 after one year were positively correlated with changes in the mucus score (r = 0.742, p = 0.007).Conclusion: This study has limitations, including its single-arm observational design and the small sample size. However, BT led to a symptomatic improvement in patients with severe asthma. The validated “√WA at Pi10” metric on CT effectively evaluated the therapeutic response in Japanese asthma patients after BT.Keywords: asthma, bronchial thermoplasty, chest computed tomography, asthma control questionnaire, √WA at Pi10

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Introduction: Myeloid-derived suppressor cell (MDSC) exhibits immunosuppressive functions and affects cancer progression, but its relationship with prostate cancer remains unclear. We elucidated the association of polymorphonuclear MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC) levels of the total peripheral blood mononuclear cells (PBMCs) with prostate cancer progression and evaluated their roles as prognostic indicators., Methods: We enrolled 115 patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC, n = 62), metastatic hormone-sensitive prostate cancer (mHSPC, n = 23), and metastatic castration-resistant prostate cancer (mCRPC, n = 30). Subsequently, the proportions of MDSCs in each disease progression were compared. Log-rank tests and multivariate Cox regression analyses were performed to ascertain the associations of overall survival., Results: The patients with mCRPC had significantly higher PMN-MDSC percentage than those with nmHSPC and mHSPC (P = 7.73 × 10 -5 and 0.0014). Significantly elevated M-MDSC levels were observed in mCRPC patients aged <70 years (P = 0.016) and with a body mass index (BMI) <25 kg/m 2 (P = 0.043). The high PMN-MDSC group had notably shorter median survival duration (159 days) than the low PMN-MDSC group (768 days, log-rank P = 0.018). In the multivariate analysis including age, BMI, and MDSC subset, PMN-MDSC was significantly associated with prognosis (hazard ratios, 3.48; 95% confidence interval: 1.05-11.56, P = 0.042)., Discussion: PMN-MDSC levels are significantly associated with mCRPC prognosis. Additionally, we highlight the remarkable associations of age and BMI with M-MDSC levels in mCRPC, offering novel insights into MDSC dynamics in prostate cancer progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kobayashi, Nagata, Hachiya, Wakita, Ikehata, Takahashi, China, Shimizu, Lu, Jin, Lu, Ide and Horie.)

Ionizing radiation (IR) causes DNA damage, particularly DNA double-strand breaks (DSBs), which have significant implications for genome stability. The major pathways of repairing DSBs are homologous recombination (HR) and nonhomologous end joining (NHEJ). However, the repair mechanism of IR-induced DSBs in embryos is not well understood, despite extensive research in somatic cells. The externally developing aquatic organism, Xenopus tropicalis, serves as a valuable model for studying embryo development. A significant increase in zygotic transcription occurs at the midblastula transition (MBT), resulting in a longer cell cycle and asynchronous cell divisions. This study examines the impact of X-ray irradiation on Xenopus embryos before and after the MBT. The findings reveal a heightened X-ray sensitivity in embryos prior to the MBT, indicating a distinct shift in the DNA repair pathway during embryo development. Importantly, we show a transition in the dominant DSB repair pathway from NHEJ to HR before and after the MBT. These results suggest that the MBT plays a crucial role in altering DSB repair mechanisms, thereby influencing the IR sensitivity of developing embryos., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

In a previous study, we developed a novel analytical method to directly and simultaneously detect taste- and odor-active compounds using graphite carbon black (GCB)-assisted laser desorption ionization mass spectrometry (LDI-MS). In this study, we aimed to evaluate food quality using a variety of soy sauces using the method to discriminate each product. Graphite carbon black-laser desorption ionization-mass spectrometry allowed the provision of hundreds of MS peaks derived from soy sauces in both positive and negative modes without any tedious sample pretreatments. Principal component analysis using the obtained MS peaks clearly distinguished three soy sauce products based on the manufacturing countries (Japan, China, and India). Moreover, this method identified distinct MS peaks for discrimination, which significantly correlated with their quantitative amounts in the products. Thus, GCB-LDI-MS analysis was established as a simple and rapid technique for food analysis, illustrating the chemical patterns of food products., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

The patient was a 71-year-old male whose chief complaint was a scrotum mass. The mass had gradually increased in size without any associated symptoms. The physical examination revealed a pedunculated, radish brown, and elastic soft tumor (4. 5×3. 5×3. 0 cm) in the right scrotum. Blood chemical analysis of HbA1c and squamous carcinoma antigen were 8. 3% and 38. 4 ng/ml (≦1. 5), respectively. This tumor was successfully treated with surgical resection. Histopathological examination showed condyloma acuminatum without malignant findings. Giant condyloma acuminatum commonly affects the genital and perianal areas. An immunocompromised state generally exists in the background of the patients.

Objective: Assisted reproductive technology (ART), especially frozen-thawed embryo transfer (FET) in a hormone replacement cycle (HRC), is a risk factor for placenta accreta spectrum (PAS). This study aimed to clarify the risk factors for PAS related to the maternal background and ART techniques in pregnancies achieved after FET in an HRC., Study Design: We performed a case-control study in two tertiary perinatal centres in Japan. Among 14,028 patients who delivered at ≥24 weeks of gestation or were transferred after delivery to two tertiary perinatal centres between 2010 and 2021, 972 conceived with ART and 13,056 conceived without ART. PAS was diagnosed on the basis of the FIGO classification for the clinical diagnosis of PAS or retained products of conception after delivery at ≥24 weeks of gestation. We excluded women with fresh embryo transfer, FET with a spontaneous ovulatory cycle, a donor oocyte cycle, and missing details of the ART treatment. Finally, among women who conceived after FET in an HRC, 62 with PAS and 340 without PAS were included in this study. Multivariate logistic regression models were used for case-control comparisons, with adjustment for maternal age at delivery, parity, endometriosis or adenomyosis, the number of previous uterine surgeries of caesarean section, myomectomy, endometrial polypectomy or endometrial curettage, placenta previa, the stage of transferred embryos, and endometrial thickness at the initiation of progestin administration., Results: PAS was associated with ≥2 previous uterine surgeries (adjusted odds ratio, 3.57; 95 % confidence interval, 1.60-7.97) and the stage of embryo transfer (blastocysts: adjusted odds ratio, 2.89; 95 % confidence interval, 1.15-7.26). In patients with <2 previous uterine surgeries, PAS was associated with an endometrial thickness of <7.0 mm (adjusted odds ratio, 5.18; 95 % confidence interval, 1.10-24.44)., Conclusion: Multiple uterine surgeries and the transfer of blastocysts are risk factors for PAS in pregnancies conceived after FET in an HRC. In women with <2 previous uterine surgeries, a thin endometrium before FET is also a risk factor for PAS in these pregnancies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Low testosterone levels in men have been linked to decreased physical and mental function, as well as a reduced quality of life. Previous prospective observational studies have suggested an association between testosterone and sleep traits, but the causality of this relationship remains unclear. We aimed to explore the potential causal link between genetically determined sleep traits and testosterone levels in men using Mendelian randomization (MR) analysis from the UK Biobank dataset. Our exposures were genetic variants associated with sleep traits (chronotype and sleep duration), whereas our outcomes were traits of sex steroid hormones (total testosterone, TT; bioavailable testosterone, BAT; and sex hormone-binding globulin, SHBG). We employed inverse variance weighted (IVW) and weighted median (WM) methods to assess the causal associations. The IVW method offers a robust estimate of causality, whereas the WM method provides reliable results even when some genetic variants are invalid instruments. Our main analysis involving sex steroid hormones and chronotype identified 155 chronotype-related variants. The primary findings from the analysis, which used chronotype as the exposure and sex steroid hormones as the outcomes, showed that a genetically predicted chronotype score was significantly associated with an increased levels of TT (association coefficient β, 0.08; 95% confidence interval [CI], 0.02-0.14; P = 0.008) and BAT (β, 0.08; 95% CI, 0.02-0.14; P = 0.007), whereas there was no significant association with SHBG (β, 0.01; 95% CI, -0.02-0.03; P = 0.64). Meanwhile, MR analysis of sex steroid hormones and sleep duration was performed, and 69 variants associated with sleep duration were extracted. There were no significant association between sleep duration and sex steroid hormones (TT, P = 0.91; BAT, P = 0.82; and SHBG, P = 0.95). Our data support a causal association between chronotype and circulating testosterone levels in men. These findings underscore a potential causal relationship between chronotype and testosterone levels in men, suggesting that lifestyle adjustments are crucial for men's health. Recognizing factors that influence testosterone is essential. One limitation of this study is the use of one-sample MR, which can introduce potential bias due to non-independence of genetic associations for exposure and outcome. In conclusion, our findings indicate that a morning preference is correlated with circulating testosterone levels, emphasizing the potential impact of lifestyle habits on testosterone levels in men., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ichikawa, Kobayashi, Hachiya, Ikehata, Isotani, Ide and Horie.)

Background: Leukocyte telomere length (LTL) and myeloid-derived suppressor cells (MDSC) are associated with aging and the development and progression of cancer. However, the exact nature of this relationship remains unclear. Our study aimed to investigate the potential of LTL and MDSC as diagnostic biomarkers for prostate cancer while also seeking to deepen our understanding of the relationship of these potential biomarkers to each other., Methods: Our study involved patients undergoing a prostate biopsy. We analyzed the relative LTL in genomic DNA obtained from peripheral blood leukocytes as well as the percentage of MDSC and their subtypes in peripheral blood mononuclear cells (PBMC). Our evaluation focused on examining the relationship between LTL and MDSC and pathological diagnoses as well as investigating the correlation between LTL and MDSC levels., Results: In our study of 102 participants, 56 were pathologically diagnosed with localized prostate cancer (cancer group), while 46 tested negative (control group). The cancer group exhibited significantly shorter LTL in comparison to the control group ( p = 0.024). Additionally, the cancer group showed a tendency towards a higher percentage of monocytic MDSC (M-MDSC), although this difference did not reach statistical significance ( p = 0.056). Our multivariate logistic regression analysis revealed that patients with shorter LTL and higher percentages of M-MDSC had a 2.98-fold (95% CI = 1.001-8.869, p = 0.049) and 3.03-fold (95% CI = 1.152-7.977, p = 0.025) increased risk of prostate cancer diagnosis, respectively. There was also a significant negative correlation between LTL and M-MDSC. (r = -0.347, p < 0.001)., Conclusions: Our research has established a correlation between LTL and MDSC in patients undergoing biopsy for prostate cancer. Notably, we observed that individuals with localized prostate cancer tend to have shorter LTL and a higher percentage of M-MDSC prior to their diagnosis. These findings suggest that LTL and M-MDSC could potentially serve as adjunctive biomarkers for the early diagnosis of prostate cancer.

The aim of this study is to examine the correlation between aging, serum total testosterone and biomarkers of multiple organ functions in men. The participants consisted of 12,547 outpatients, whose serum testosterone level was measured. A multiple regression analysis was conducted to determine whether biomarkers including hemoglobin (Hb), hematocrit (Hct), luteinizing hormone (LH), follicle stimulating hormone (FSH), alkaline phosphatase (ALP), albumin (ALB), creatinine (Cre), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose (Glu), C-reactive protein (CRP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) values were associated with serum total testosterone concentration. Significant correlations (p < 0.05) were found between total testosterone and Hb, Hct, LH, FSH, ALP, ALB, TG, HDL-C, AST, ALT, Glu, and CRP. In addition, significant correlations (p < 0.05) were found between Hb, Hct, LH, FSH, ALP, ALB, TG and HDL-C associated with [age × testosterone]. This large-scale study provided new insights into correlations between serum testosterone and biomarkers associated with age-related diseases, suggesting that testosterone is especially important for maintaining homeostasis in aging males. Thus, hypogonadism in elderly patients may be associated with multiple organ dysfunctions.

Enzalutamide is a second-generation androgen receptor inhibitor that increases overall survival (OS) rates in patients with metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the efficacy of circulating tumor cell (CTC) status as a prognostic biomarker following enzalutamide administration. A retrospective subgroup analysis and prognostic survey were conducted on 43 patients with mCRPC and bone metastases treated in Juntendo University-affiliated hospitals from 2015 to 2022. Patients were treated with 160 mg enzalutamide daily. CTC analyses on blood samples were performed regularly before and every three months after treatment. The relationship between the patients' clinical factors and the OS rate was analyzed using the log-rank test; the median OS was 37 months. Patients with no detected CTCs at baseline showed significantly longer OS than those with detectable CTCs at baseline. Furthermore, patients demonstrating negative reversion of CTCs during enzalutamide treatment had significantly longer OS than patients with CTC-positivity. Two biomarkers-higher hemoglobin at baseline and achieving negative reversion of CTCs-were significantly associated with prolonged OS. This study suggests that patients achieving CTC-negative reversion during treatment for mCRPC with bone metastases exhibit improved long-term OS. Chronological measurement of CTC status might be clinically useful in the treatment of mCRPC.

Testosterone is crucial in regulating several body functions in men, including metabolic, sexual, and cardiovascular functions, bone and muscle mass, and mental health. Therefore, optimizing testosterone levels in men is an important step to maintaining a healthy body and mind, especially as we age. However, traditional testosterone replacement therapy has been shown to lead to male infertility, caused by negative feedback in the hypothalamic-pituitary-gonadal (HPG) axis. Recent advances in research have led to the discovery of many new methods of administration, which can have more or less suppressive effects on the HPG axis. Also, the usage of ancillary medications instead of or after testosterone administration might help maintain fertility in hypogonadal patients. The goal of this narrative review is to summarize the newest methods for optimizing fertility parameters in patients undergoing treatment for hypogonadism and to provide the necessary information for healthcare providers to make the right treatment choices.

Background: Obstructive sleep apnea (OSA) occurs more commonly in asthma patients than in the general population because these conditions share some comorbidities. In Japan, the prevalence of OSA in the general population is reported to be approximately 20%; however, few reports have described the prevalence of OSA in asthma patients. Furthermore, the characteristics of Japanese patients with OSA and asthma are not clear., Methods: Adult asthma patients were recruited from the outpatient departments of our institution between August 31, 2017, and March 31, 2019. In all included patients, the presence and severity of OSA were evaluated by the Epworth Sleepiness Scale (ESS) and a home sleep test (HST) using portable polysomnography (PSG). The rate of coexisting OSA in asthma patients and the characteristics of those patients according to the severity of OSA were investigated., Results: Fifty-three patients were included. OSA was detected in 36 (67.9%) patients (mild, n = 15; moderate, n = 14; and severe, n = 7). Patients with OSA had significantly higher body mass index, Brinkman index, apnea-hypopnea index (AHI), and 3% oxygen desaturation index (ODI) values in comparison to those without OSA, while the percentage of the predicted value of forced vital capacity (%FVC) and lowest SpO 2 levels were significantly lower. As the severity of OSA increased, age, brain natriuretic peptide level, AHI, and 3%ODI increased, and in contrast, FVC, %FVC, forced expiratory volume in one second (FEV 1 ), percentage of the predicted value of FEV 1 (%FEV 1 ), Epworth Sleepiness Scale (ESS), 3%ODI, and lowest SpO 2 levels decreased. In particular, the fact that the ESS value was inversely correlated with the severity of OSA in our patients was different from the general characteristics of OSA. Moreover, the AHI value was negatively correlated with FVC, %FVC, FEV 1 , and %FEV 1 . BMI was the only independent factor for the presence of OSA, and for asthma severity (FEV1, % of predicted), there was a weak correlation with smoking history., Conclusions: This is the first report to investigate the prevalence of OSA in Japanese asthma patients, using an HST. This study suggests that an HST should be performed in addition to the sleep interview for asthma patients with refractory disease, a low pulmonary function, advanced age, and high BMI because the more severe the OSA, the lower the ESS value may be., (© 2024. The Author(s).)

Background: The culture of excessively long overtime work in Japan has not been recently addressed. New legislation on working hours, including a limitation on maximum overtime work for physicians, will be enforced in 2024. This study was performed to elucidate the working conditions of full-time hospital physicians and discuss various policy implications., Methods: A facility survey and a physician survey regarding physicians' working conditions were conducted in July 2022. The facility survey was sent to all hospitals in Japan, and the physician survey was sent to all physicians working at half of the hospitals. The physicians were asked to report their working hours from 11 to 17 July 2022. In addition to descriptive statistics, a multivariate logistic regression analysis on the factors that lead to long working hours was conducted., Results: In total, 11,466 full-time hospital physicians were included in the analysis. Full-time hospital physicians worked 50.1 h per week. They spent 45.6 h (90.9%) at the main hospital and 4.6 h (9.1%) performing side work. They spent 43.8 h (87.5%) on clinical work and 6.3 h (12.5%) on activities outside clinical work, such as research, teaching, and other activities. Neurosurgeons worked the longest hours, followed by surgeons and emergency medicine physicians. In total, 20.4% of physicians were estimated to exceed the annual overtime limit of 960 h, and 3.9% were estimated to exceed the limit of 1860 h. A total of 13.3% and 2.0% exceeded this level only at their primary hospital, after excluding hours performing side work. Logistic regression analysis showed that male, younger age, working at a university hospital, working in clinical areas of practice with long working hours, and undergoing specialty training were associated with long working hours after controlling for other factors., Conclusions: With the approaching application of overtime regulations to physicians, a certain reduction in working hours has been observed. However, many physicians still work longer hours than the designated upper limit of overtime. Work reform must be further promoted by streamlining work and task-shifting while securing the functions of university hospitals such as research, education, and supporting healthcare in communities., (© 2024. The Author(s).)

Objectives: Although vaccines have promoted the socioeconomic normalization of COVID-19, adverse effects on work performance due to the post-vaccination side effects have been reported. Thus, we examined the relationship between the status of going to work the day following vaccination as a post-vaccination employment consideration and work performance among Japanese workers in the manufacturing industry., Methods: Overall, 1273 employees who received the COVID-19 vaccine in a Japanese manufacturing district were surveyed using a self-administered web-based questionnaire that included fever, fatigue, workplace attendance the day after vaccination, work performance 1 week after vaccination, and demographic and occupational characteristics (age, gender, work style, and psychological distress [K6 scale]). The effects of fatigue and attendance on declining work performance were estimated using a linear mixed model, with individuals as random effects and the rest as fixed effects., Results: After adjusting for demographic and occupational characteristics, the third-order interaction of fever, fatigue, and attendance on the day following vaccination was significant. The nonattendance group had a significantly higher work performance than the attendance group in those without fever and long-term fatigue (F1,1559 = 4.9, P = .026) and with fever and short-term fatigue (F1,1559 = 5.9, P = .015). Fever and workplace attendance the following day were not directly related to a decrease in work performance after vaccination., Conclusions: Our findings suggest that nonattendance at the workplace is associated with work performance due to the side effects after COVID-19 vaccination., (© The Author(s) [2024]. Published by Oxford University Press on behalf of Journal of Occupational Health.)

Aim: Tongue strength plays an important role in the process of food intake, and low tongue pressure has been associated with aspiration pneumonia, cognitive decline, and mortality. However, special equipment for tongue pressure measurement is uncommon in general practice. Recently, the serum creatinine-to-cystatin C (Cr/CysC) ratio has been validated as a marker of muscle volume mass. Thus, we aimed to investigate the association of the serum Cr/CysC ratio with tongue pressure in a cross-sectional study., Methods: This single-center, cross-sectional study enrolled 73 participants (mean age, 71.7 years; men, 49.3%) who regularly attended the hospital for treatment of chronic disease. A tongue pressure of <30 kPa was defined as low tongue pressure. We evaluated the relationships between the serum Cr/CysC ratio and tongue pressure using multiple regression analysis., Results: The serum Cr/CysC ratio was correlated with tongue pressure (R 2  = 0.25, P < 0.0001). In multiple regression analyses adjusted for confounders including age, sex, body mass index, and serum albumin, the association remained significant (P = 0.0001). In logistic analyses, the multivariable-adjusted odds ratios of the Cr/CysC ratio for tertiles 1 and 2 compared with tertile 3 for low tongue pressure were 7.81 (95% confidence interval, 1.45-51.73) and 2.71 (95% confidence interval, 0.60-13.19), respectively., Conclusions: We demonstrated that a decreased serum Cr/CysC ratio was associated with a higher risk of low tongue pressure. Our findings suggest that this simple serum surrogate marker may be a first step toward an intervention for oral function by general practitioners. Geriatr Gerontol Int 2024; 24: 102-108., (© 2023 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

To date, research on ethical issues regarding care robots for older adults, family caregivers, and care workers has not progressed sufficiently. This study aimed to build a model that universally explains the relationship between the use of care robots and ethical awareness, such as regarding personal information and privacy protection in home care. We examined data obtained from cross-sectional surveys conducted in Japan (n=528), Ireland (n=296), and Finland (n=180). We performed a confirmatory factor analysis by using responses to 11 items related to the ethical use of care robots. We evaluated the model based on the chi-square to degrees of freedom ratio, the comparative fit index, and the root mean square error of approximation. Subsequently, we compared the model with the Akaike's information criterion. Ten items were adopted in the final model. There were 4 factors in the model: 'acquisition of personal information', 'use of personal information for medical and long-term care', 'secondary use of personal information', and 'participation in research and development'. All factor loadings of the final model ranged between 0.63 and 0.92, which were greater than 0.6, showing that the factors had a high influence on the model. The final model was applied to each country; the fit was relatively good in Finland and poor in Ireland. Although the three countries have different geographies, cultures, demographics, and systems, this study showed that the impact of ethical issues regarding the use of care robots in home care can be universally explained by the same model., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Taguchi et al. reported that postmenstrual age (PMA) is a promising factor in describing and understanding the developmental change of caffeine (CAF) clearance. The aim of the present study was to quantify how developmental changes occur and to determine the effect of the length of the gestational period on CAF clearance. We performed a nonlinear mixed effect model (NONMEM) analysis and evaluated the fit of six models. A total of 115 samples were obtained from 52 patients with a mean age of 34.3 ± 18.2 d. The median values of gestational age (GA) and postnatal age (PNA) were 196 and 31 d, respectively. Serum CAF levels corrected for dose per body surface area (BSA) (C/D ratio BSA ) were dependent on PMA rather than PNA, which supports the findings of a previous study. NONMEM analysis provided the following final model of oral clearance: CL/F = 0.00603∙WT∙∙0.877 GA   ≤   196 L/h. This model takes into account developmental changes during prenatal and postnatal periods separately. The model successfully described the variation in clearance of CAF. Our findings suggest that the dosage of CAF in preterm infants should be determined based not only on body weight (WT) but also on both PNA and GA.