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Ensitrelvir is a nonpeptide 3CL protease inhibitor used for coronavirus disease 2019 treatment. Four crystalline forms of ensitrelvir, metastable (Form I), acetonate (Form II), stable (Form III), and hydrate (Form IV), have been analyzed as pharmaceutical crystals. Their rank order of solubility is Form I > IV > III. Form III is the stable crystal with a significantly lower solubility than that predicted from its log P value of 2.7. Here, single-crystal structural analysis revealed strong intermolecular interactions between the triazine (acidic) and triazole (basic) groups of Form III not Forms I and IV. Multicomponent crystals were also designed to improve the solubility by altering the intermolecular interactions in Form III. Slurry conversion with equal molar ratios of ensitrelvir and fumaric acid successfully induced the formation of a novel cocrystal (Form V). Fumaric acid inhibited the triazine-triazole interactions, and dissolution of Form V was approximately 8- and 13-fold higher than that of Form III in pH 1.2 and 6.8 media, respectively. Furthermore, Form V exhibited an approximately 16-fold higher flux value than that of Form III. Therefore, alterations in intermolecular interactions via cocrystallization significantly enhance the dissolution and permeation of ensitrelvir.

Seven new polyketides [moringols I-VII (1-7)], a new alkaloid [moringamine I (8)], and seven known compounds (9-15) were isolated from the fungus Curvularia moringae JKYM-KR4. The planar chemical structures and relative configurations of the new compounds were elucidated by high-resolution mass spectrometry, 1D and 2D NMR spectroscopy, and DP4+ analysis using the calculated 13 C NMR chemical shifts. For moringols I and II (1 and 2), the planar chemical structures and relative configurations were confirmed using X-ray crystallography. The absolute configurations of 1-6 and 8 were determined by ECD calculations. Among the isolated compounds, terpestacin (14) moderately inhibited the proliferation of HT-29 cells., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Acute exercise improves cognitive performance. However, it remains unclear what triggers cognitive improvement. Electrical muscle stimulation (EMS) facilitates the examination of physiological changes derived from peripheral muscle contraction during exercise. Thus, we compared the effects of EMS and voluntary exercise at low- or moderate-intensity on reaction time (RT) in a cognitive task to understand the contribution of central and peripheral physiological factors to RT improvement., Methods: Twenty-four young, healthy male participants performed a Go/No-Go task before and after EMS/exercise. In the EMS condition, EMS was applied to the lower limb muscles. In the low-intensity exercise condition, the participants cycled an ergometer while maintaining their heart rate (HR) at the similar level during EMS. In the moderate-intensity exercise condition, exercise intensity corresponded to ratings of perceived exertion of 13/20. The natural log-transformed root mean square of successive differences between adjacent inter-beat (R-R) intervals (LnRMSSD), which predominantly reflects parasympathetic HR modulation, was calculated before and during EMS/exercise., Results: RT improved following moderate-intensity exercise (p = 0.002, Cohen' d = 0.694), but not following EMS (p = 0.107, Cohen' d = 0.342) and low-intensity exercise (p = 0.076, Cohen' d = 0.380). Repeated measures correlation analysis revealed that RT was correlated with LnRMSSD (Rrm(23) = 0.599, p = 0.002) in the moderate-intensity exercise condition., Conclusion: These findings suggest that the amount of central neural activity and exercise pressor reflex may be crucial for RT improvement. RT improvement following moderate-intensity exercise may, at least partly, be associated with enhanced sympathetic nervous system activity., Competing Interests: Declarations Conflict of interest The authors declare that there is no conflict of interest. Ethics approval This study was approved by the University of Electro-Communications’ Human Ethics Committee (No: 19003). The study conformed to the standards set by the latest revision of the Declaration of Helsinki, except for registration in the database. Consent to participate Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bioelectrical impedance analysis (BIA) is a widely used method for estimating body composition, and its accuracy may be influenced by various factors, including bladder filling. This study aims to investigate the impact of bladder filling on the accuracy of BIA measurements. An experimental crossover study was conducted with sedentary young adults. The influence of bladder filling on total body water (TBW), fat mass (FM), fat-free mass (FFM), and basal metabolic rate (BMR) was assessed. Participant in underwear followed an overnight fast. They were instructed to abstain from vigorous physical activity and alcohol for at least 24 h prior to the session. The results obtained from single-frequency and multi-frequency BIA devices were compared. The findings suggest that bladder filling does not affect measured impedance; however, changes in weight following bladder voiding influenced derived BIA results. Specifically, TBW, FM, and BMR values significantly reduced after voiding ( p < 0.05). Furthermore, the study found poor agreement between single-frequency and multi-frequency BIA devices, indicating that they are not interchangeable. Bladder filling does affect BIA measurements, not clinically meaningful. Further research is needed to explore the implications of these findings for clinical practice and research protocols.

Mushrooms are the fruiting bodies of fungi and are important reproductive structures that produce and disseminate spores. The Pri3 gene was originally reported to be specifically expressed in the primordia (a precursor to the mature fruiting body) of the edible mushroom Cyclocybe aegerita. Here, we cloned a Pri3-related cDNA from Cyclocybe cylindracea, another species in the same genus, and showed that the gene is specifically expressed at the pileus surface of the immature fruiting body but not in the primordia. Immunohistochemistry showed that the translated protein is secreted into a polysaccharide layer of the pileus surface. The recombinant C-terminal Cys-rich domain of the protein showed antifungal activity against three filamentous fungi and inhibited hyphal growth and conidiogenesis. These results suggest that the PRI3-related protein of C. cylindracea, named cylindracin, plays an important role in the defense against pathogens., (© 2024 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Demonstrating drug efficacy in slowing kidney disease progression requires large clinical trials when targeting participants with an early stage of chronic kidney disease (CKD). In this randomized, parallel-group, open-labeled trial (CANPIONE study), we assessed the effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin using the individual's change in estimated glomerular filtration rate (eGFR) slope before (pre-intervention slope) and during treatment (chronic slope). We randomly assigned (1:1) participants with type 2 diabetes, urinary albumin-to-creatinine ratio (UACR) of 50 to under 300 mg/g, and an eGFR of at least 45 ml/min/1.73m 2 to receive canagliflozin or guideline-recommended treatment except for SGLT2 inhibitors (control). The first and second primary outcomes were the geometric mean percentage change from baseline in UACR and the change in eGFR slope, respectively. Of 98 randomized participants, 96 received at least one study treatment. The least-squares mean change from baseline in log-transformed geometric mean UACR was significantly greater in the canagliflozin group than the control group (between group-difference, -30.8% (95% confidence interval -42.6 to -16.8). The between-group difference (canagliflozin group - control group) of change in eGFR slope (chronic - pre-intervention) was 4.4 (1.6 to 7.3) ml/min/1.73 m 2 per year, which was more pronounced in participants with faster eGFR decline. In summary, canagliflozin reduced albuminuria and the participant-specific natural course of eGFR decline in participants with type 2 diabetes and microalbuminuria. Thus, the CANPIONE study suggests that the within-individual change in eGFR slope may be a novel approach to determine the kidney protective potential of new therapies in early stages of CKD., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objective: Patients with chronic kidney disease reportedly have decreased muscle oxygen utilization, which most substantially decreases exercise capacity, followed by cardiac reserve. However, determinants of longitudinal changes in exercise capacity in patients on hemodialysis and the effects of long-term exercise interventions are unknown. This study was conducted to clarify these concerns., Methods: This was a prospective cohort study. Patients on hemodialysis that were not hospitalized were followed from baseline up to 2 years, and cardiopulmonary exercise testing results, including peak oxygen uptake, peak work rate, heart rate reserve, and ventilatory equivalent for carbon dioxide slope, as well as implementation of exercise interventions were assessed. Based on the 2-year change in peak oxygen uptake, they were divided into improvement or declined groups., Results: Forty-five patients who were not hospitalized completed the follow-up were analyzed. In the improvement group, the variation was determined by an increase in peak work rate, which is a peripheral factor (partial regression coefficient 0.08 [95% CI = 0.01 to 0.16]), while in the decline group, the variation was determined by a decrease in the ventilatory equivalent for carbon dioxide slope, which is a cardiac factor (partial regression coefficient = -0.12; 95% CI = -0.21 to -0.03). Moreover, exercise intervention was associated with the change in peak oxygen uptake (partial regression coefficient = 3.09; 95% CI = 1.45 to 4.72)., Conclusion: Exercise intolerance even in patients on hemodialysis that were not hospitalized and stable progressed over time with deterioration of cardiac reserve, whereas exercise interventions were associated with improved exercise capacity through enhanced peripheral function., Impact: The results support the early measurement of cardiopulmonary or skeletal muscle reserve through cardiopulmonary exercise testing and the implementation of long-term exercise interventions based on the measurement results to address the potential deterioration in exercise capacity associated with reduced cardiac reserve, even in patients on hemodialysis that are asymptomatic and stable., (© 2024 American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Covert hepatic encephalopathy (CHE) significantly impacts the quality of life and prognosis in patients with liver cirrhosis. This study aims to analyze the prevalence and risk factors of CHE to identify high-risk patients who would benefit from therapeutic interventions., Methods: This single-center, retrospective observational study included 126 patients without a history of overt hepatic encephalopathy (OHE). CHE was defined as a score above the age-based cutoff value in the Stroop test. Factors associated with the occurrence of CHE and the subsequent development of OHE were evaluated., Results: CHE was detected in 47 patients (37.3%). A multiple logistic regression analysis identified serum zinc levels (per + 1 µg/dL, odds ratio 0.95, P = 0.0007) as the only risk factor associated with CHE, with a cutoff value of 60 µg/dL (AUC 0.71, P = 0.0001). Neither blood ammonia levels nor liver function were predictive of CHE. During a median observation period of 211 days, OHE developed in 18 patients (14.3%). The administration of more than 20 mg of furosemide was identified as a risk factor for developing OHE (hazard ratio 23.52, P = 0.0207)., Conclusion: Cirrhotic patients with serum zinc levels below 60 µg/dL exhibit a high risk of developing CHE, regardless of blood ammonia levels. These patients face a significant risk of developing OHE. Therefore, early zinc supplementation is recommended for the prevention of OHE, particularly for those prescribed 20 mg or more of furosemide., (© 2024. Japanese Society of Gastroenterology.)

Chlorophyll a serves as a photosynthetic pigment in plants. Its degradation is initiated by the extraction of the central Mg by the Mg-dechelatase enzyme, which is encoded by Stay-Green (SGR). Plant SGR is believed to be derived from bacterial SGR homolog obtained through horizontal gene transfer into photosynthetic eukaryotes. However, it is not known how the bacterial SGR homolog was modified to function in plants. To assess its adaptation mechanism in plants, a bacterial SGR homolog derived from the Anaerolineae bacterium SM23&#95;63 was introduced into plants. It was found that the bacterial SGR homolog metabolized chlorophyll in plants. However, its chlorophyll catabolic activity was lower than that of plant SGR. Recombinant proteins of the bacterial SGR homolog exhibited higher activity than those of the plant SGR. The reduced chlorophyll catabolic activity of bacterial SGR homologs in plants may be associated with low hydrophobicity of the entrance to the catalytic site compared to that of plant SGR. This hinders the enzyme access to chlorophyll, which is localized in hydrophobic environments. This study offers insights into the molecular changes underlying the optimization of enzyme function., 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 Elsevier Masson SAS. All rights reserved.)

Melatonin is synthesized in and secreted from the pineal glands and regulates circadian rhythms. Although melatonin has been reported to modulate the activity of ion channels in several tissues, its effects on pineal ion channels remain unclear. In the present study, the effects of melatonin on voltage-gated K + (K V ) channels, which play a role in regulating the resting membrane potential, were examined in rat pinealocytes. The application of melatonin reduced pineal K V currents in a concentration-dependent manner (IC 50 = 309 µM). An expression analysis revealed that K V 4.2 channels were highly expressed in rat pineal glands. Melatonin-sensitive currents were abolished by the small interfering RNA knockdown of K V 4.2 channels in rat pinealocytes. In human embryonic kidney 293 (HEK293) cells expressing K V 4.2 channels, melatonin decreased outward currents (IC 50 = 479 µM). Inhibitory effects were mediated by a shift in the voltage dependence of steady-state inactivation in a hyperpolarizing direction. This inhibition was observed even in the presence of 100 nM luzindole, an antagonist of melatonin receptors. Melatonin also blocked the activity of K V 4.3, K V 1.1, and K V 1.5 channels in reconstituted HEK293 cells. The application of 1 mM melatonin caused membrane depolarization in rat pinealocytes. Furthermore, K V 4.2 channel inhibition by 5 mM 4-aminopyridine attenuated melatonin secretion induced by 1 µM noradrenaline in rat pineal glands. These results strongly suggest that melatonin directly inhibited K V 4.2 channels and caused membrane depolarization in pinealocytes, resulting in a decrease in melatonin secretion through parasympathetic signaling pathway. This mechanism may function as a negative-feedback mechanism of melatonin secretion in pineal glands. NEW & NOTEWORTHY Melatonin is a hormone that is synthesized in and secreted from the pineal glands, which regulates circadian rhythms. However, the effects of melatonin on pineal ion channels remain unclear. The present study demonstrated that melatonin directly inhibited voltage-gated potassium K V 4.2 channels, which are highly expressed in rat pinealocytes, and induced membrane depolarization, resulting in a decrease in melatonin secretion. This mechanism may function as a negative-feedback mechanism of melatonin secretion in pineal glands.

Purpose: Young caregivers experience, on average, poorer mental health outcomes than non-caregiving young people. However, it is unknown to what extent these effects differ with age, or among short-term versus long-term caregivers. Using repeated assessment of young caregiving across multiple waves of a prospective adolescent cohort study, we conducted repeated cross-sectional analyses of caregiver status and contemporaneous depressive symptoms, self-harm, and suicidality in early to middle adolescence., Methods: Four waves of questionnaire data from a large, longitudinal population-based cohort study (Tokyo Teen Cohort) were analyzed. Caregiver status was collected from participants aged 10, 12, 14, and 16 years. Mental health outcomes assessed were depressive symptoms, self-harm and suicidal feelings. Logistic regression analyses were conducted assessing effects of a) young caregiver status and b) new, long-term, and ex-caregiver 2-year categorizations on mental health outcomes at 12, 14, and 16 years, both unadjusted and adjusted for potential confounders (sex, low income, single-parent household, and parental distress)., Results: Depressive symptoms were elevated among long-term caregivers at 14 years (unadjusted odds ratio (uOR): 3.11 [1.33-7.27], adjusted odds ratio (aOR): 2.49 [1.03-5.99]). Borderline associations between long-term caregiving and self-harm (uOR: 3.14 [1.06-9.35], aOR: 2.51 [0.82-7.63]) and suicidal feelings (uOR: 2.49 [0.98-6.34], aOR: 2.06 [0.80-5.33]) were detected at 16 years. No associations were found at age 12 years in primary analyses; sensitivity analyses indicated possible increased depressive symptoms., Discussion: Young caregivers with long-term caregiving roles are at the greatest risk for negative mental health outcomes, with effects concentrated in later adolescence. These findings highlight urgent need for early identification and practical and psychological support for young people shouldering caregiving burdens., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The association between surgical performance ratings and clinical outcomes in robotic surgery is poorly understood. Additionally, no studies have reported on the relationship between the surgeon's initial case-skill evaluation and the learning curve in robot-assisted surgery. We evaluated whether an objective surgical technique evaluation score for initial robot-assisted radical prostatectomy (RARP) was associated with clinical outcomes and surgeons' learning curves., Methods: Six surgeons who were trained in and started to perform RARP at our institution were included. Anonymized, unedited videos of each surgeon's 10th RARP case were evaluated by three reviewers, using modified Objective Structured Assessment of Technical Skill (OSATS) scores. We then divided the surgeons into two groups on the basis of these OSATS scores. We retrospectively compared the clinical outcomes and learning curves of the console time of the two groups for consecutive RARPs, performed from March 2018 to July 2023., Results: We analyzed 258 RARPs (43 cases/surgeon), including 129 cases performed by high-OSATS score surgeons (18.2-19.3 points) and 129 cases performed by low-OSATS score surgeons (11.9-16.0 points). Overall, the high-OSATS score group had significantly shorter operation and console times than the low-OSATS score group did (both P < 0.01) and their patients' rate of continence recovery by 3 months post-RARP was significantly higher (P = 0.03). However, complications, blood loss, and positive margins did not differ between the groups (P = 0.08, P = 0.51, and P = 0.90, respectively). The high-OSATS score group had a significantly shorter console time than the low-OSATS score group did after the 11-20 cases., Conclusions: The OSATS score in early RARP cases can predict subsequent surgical outcomes and surgeons' learning curves., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Perinatal depression is a significant concern affecting both women and men during pregnancy and postpartum periods. While maternal postpartum depression has been extensively studied, paternal depression remains under-researched despite its prevalence and impact on family well-being. This study aimed to estimate the trajectories of perinatal and postpartum depression in Japanese parents over ten years and to determine the details of the symptoms of postpartum depression for each trajectory group, considering reciprocal effects between maternal and paternal depression., Methods: A total of 789 couples used the Edinburgh Postnatal Depression Scale to rate their depressive symptoms prenatally; at 5 weeks, 3 months, 6 months, and 1 year postpartum; and then yearly thereafter until the 10th year. Parallel-process latent class growth analysis was used to group participants according to their longitudinal patterns of depressive symptoms., Results: For both mothers and fathers, four depressive symptom trajectories fit the data best and were most informative (escalating: 6.5 %; mothers low and fathers moderate: 17.2 %; mothers high and fathers low: 17.9 %; low: 58.4 %). A variance analysis showed significant class-parent interactions across anhedonia, anxiety, and depression subscales, indicating distinct patterns of depressive symptomatology., Discussion: Tailored mental health programs and universal screening using the Edinburgh Postnatal Depression Scale are recommended to address the specific needs of each trajectory class. This study contributes to the understanding of long-term depressive symptom trajectories in parents and emphasizes the necessity of comprehensive support strategies to enhance family well-being and resilience., Competing Interests: Declaration of competing interest While the dataset analyzed in this study partially overlaps with a cross-lag analysis study by Jikihara et al. (2023) examining behavioral problem scores in children's aged 3–10 years, we deemed it suitable for publication because of the distinct research objectives. The authors declare no conflict of interest. During the preparation of this work the authors used ChatGPT in order to enhance the language and ensure that the paper conforms to the standards of scholarly journals. After using this tool/service, the authors reviewed and edited the content as needed and take(s) full responsibility for the content of the publication. The data that support the findings of this study are available from the corresponding author upon reasonable request., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The change of repair efficiency of UV-induced pyrimidine dimers due to aging was examined in replicatively senesced fibroblasts. The fibroblasts with repeated passages showed the characteristics of cellular senescence, including irreversible cell cycle arrest, elevated β-galactosidase activity, and senescence-associated secretory phenotype. The incision efficiency of oligonucleotide containing UV lesions was similar regardless of cell doubling levels, but the gap filling process was impaired in replicatively senescent cells. The releases of xeroderma pigmentosum group G, proliferating cell nuclear antigen, and replication protein A from damaged sites were delayed, which might have disturbed the DNA polymerase progression. The persistent single-stranded DNA was likely converted to double-strand breaks, leading to ataxia telangiectasia-mutated phosphorylation and 53BP1 foci formation. Phosphorylated histone H2AX (γ-H2AX) induction mainly occurred in G1 phase in senescent cells, not in S phase such as in normal cells, indicating that replication stress-independent double-strand breaks might be formed. MRE11 having nuclease activity accumulated to damaged sites at early time point after UV irradiation but not released in senescent cells. The pharmacological studies using specific inhibitors for the nuclease activity suggested that MRE11 contributed to the enlargement of single-stranded DNA gap, facilitating the double-strand break formation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Thickness control of two-dimensional (2D) metal nanosheets (metallenes) has scientific significance for energy and catalyst applications, yet is unexplored owing to the lack of an efficient approach for the tailored synthesis of metallenes with controlled atomic layers. Here we report a 2D template-directed synthesis of ultrathin Pd nanosheets with well-controlled thicknesses. Molecularly thin single-crystalline Pd nanosheets with well-defined hexagonal morphologies were synthesized via a one-pot method with 2,4,6-trichlorophenyl formate. Such Pd nanosheets were used as hard templates for the tailored synthesis of the Pd nanosheets with controlled thicknesses (9, 11, 13, and 15 atomic layers). Hard X-ray photoelectron spectroscopy and density functional theory calculations revealed unique electronic states in thickness-controlled Pd nanosheets; these states included reduced surface charges to bulk, increased work functions, and decreased d -band centers. Thus, atomic layer engineering of Pd nanosheets enabled the fine-tuning of the surface electronic states to improve the hydrogen evolution reaction.

Introduction: We describe a case in which robot-assisted radical ureterectomy was performed for residual ureteral recurrence in a postoperative patient with renal pelvis cancer., Case Presentation: A 75-year-old woman underwent laparoscopic radical nephroureterectomy for left renal pelvic cancer at another hospital. During follow-up, a papillary tumor was found in the bladder on cystoscopy, and a continuous tumor was found in the residual ureter on computed tomography. Robot-assisted radical ureterectomy was performed in combination with transurethral resection of bladder tumors. To avoid urine spillage, bladder cuff excision was performed using a mechanical suture device while monitoring the interior of the bladder., Conclusion: We developed a new technique for remnant ureteral resection using cystoscopy and a vascular stapler to prevent urine dissemination and cancer seeding., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Ganglioneuroma is a well-differentiated tumor originating from neural crest cells of the sympathetic nervous system. Although benign, a few cases have been reported that ganglioneuroma can metastasize to other sites. We report a case of adrenal ganglioneuroma with para-aortic nodal metastases with low FDG and MIBG uptake. In order to avoid unnecessary wide excision or aggressive medication, it is important to consider the possibility of ganglioneuroma preoperatively even if with metastases., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Objectives: Despite the global health risk of carbapenem-resistant Enterobacterales (CRE), especially carbapenemase-producing Enterobacterales (CPE), Japan reports a significantly low frequency of CRE with a predominance of IMP-type carbapenemases. This study aimed to investigate the prevalence and characteristics of CRE isolated from hospitals in the city of Nara, Japan., Methods: We obtained 171 CRE isolates from 16 791 Enterobacterales isolated at 23 hospitals in Nara between January 2018 and December 2021. Isolates of CPE were characterized through antimicrobial susceptibility testing, the carbapenem inactivation method, PCR and DNA sequencing. Genotypic diversity of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae was determined via MLST and PFGE., Results: The prevalence of CRE between 2018 and 2021 was 1.02%, gradually decreasing from 1.13% to 0.74%. Ninety-nine isolates were identified as CPE, representing six species. Ninety-seven CPE isolates harboured bla IMP-6 , while the remaining two carried either bla IMP-1 or bla IMP-19 . Genotype analysis identified ST131 as the dominant genotype for E. coli , but none for K. pneumoniae . PFGE results suggested clonal spread of CPE in Hospital A, where CRE was isolated in high numbers ( n  = 44)., Conclusions: In this study, CRE prevalence was marginally higher than previously reported in Japan, but still low in frequency. A predominance of Enterobacterales harbouring bla IMP-6 was confirmed in Nara. The spread of CPE at Hospital A suggested the possibility of a nosocomial outbreak due to bla IMP-6 transmission via plasmids or clonal spread. Continued monitoring is crucial for effective management of CRE prevalence in the region., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Objectives: To compare isolates from deep wound and superficial swab cultures to evaluate the detectability of pathogens by each culture in Fournier's gangrene; and evaluate the association between microorganisms isolated from deep wounds and those isolated from blood or urine., Methods: Patients with Fournier's gangrene who underwent debridement between October 2006 and January 2023 were retrospectively reviewed. In addition to comparing the isolates from deep wound cultures at initial debridement with those from superficial swab, blood, and urine cultures, the relationship between the traits of the organisms from deep wounds and patient disease severity and prognosis was examined., Results: Among 25 patients, deep wound and superficial swab cultures were obtained from 25 to 18 patients, respectively. The frequency of anaerobic isolates was significantly lower in the superficial cultures than in the deep wound cultures (31/76 versus 13/56, p = 0.034). Bacteria not isolated from deep wounds were isolated from superficial cultures in 55.6 % of the patients; the concordance rate between deep and superficial cultures was 27.8 % (5/18). The positive rates of blood and urine cultures were 20.8 % and 35.7 %, respectively; all isolates from the urine and blood cultures reflected the results of the deep wound culture. No significant association was observed between the severity or mortality and the type of causative bacteria., Conclusions: Superficial swab cultures cannot be substituted for deep wound cultures in Fournier's gangrene. Although the positivity rates for blood and urine cultures were not high, they were helpful in determining antibiotic de-escalation., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Color-coded circulation is a display method that generates dynamic color-coded images based on the time of arrival of contrast agents using parametric imaging to create video displays. By cyclically displaying information in color according to the arrival time of the contrast agent at each pixel, anatomical blood vessel paths and blood flow information can be simultaneously visualized. Three-dimensional (3D) helical stents increase wall shear stress due to swirling flow and prevent intimal hyperplasia. To the best of our knowledge, there are no reports on the visualization of this swirling flow using color-coded circulation. Here, we report the use of color-coded circulation to visualize the swirling flow following the placement of a 3D helical stent in the left superficial femoral artery. Color-coded circulation may facilitate the evaluation of contrast agent distribution and blood flow, which may otherwise go undetected with digital subtraction angiography., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

To investigate the correlation between the aggregated state and photoluminescence (PL) mechanism of dual fluorescent (FL) and phosphorescent (PH) polyimides (PIs), the photophysical processes of FL-type BP-PI , PH-type DBrBP-PI , and their corresponding imide model compounds ( BP-MC and DBrBP-MC ) dispersed in poly(methyl methacrylate) (PMMA) films were analyzed at elevated pressures up to 8 GPa using a diamond anvil cell. Dibromo-substituted DBrBP-MC demonstrated a shorter wavelength absorption than BP-MC owing to the larger dihedral angle in the biphenyl moiety. Both MCs exhibited red-shifts in their absorption spectra with increasing pressure, indicating planarization occurred at the biphenyl moieties associated with the compression of the free volume in PMMA. The PL intensity of BP-MC increased with increasing pressure, while its quantum yield (Φ PL ) decreased sharply due to the enhanced energy transfer via the Förster mechanism. In contrast, the PH quantum yield (Φ PH ) of DBrBP-MC monotonically increased at lower pressures, while it showed excitation wavelength-dependent behaviors at higher pressures: Φ PH remained unchanged under excitation at 340 nm but gradually increased under excitation at 365 nm. This fact suggests that, at higher pressures, 365 nm excitation promoted intersystem crossing (ISC) from excited singlet states at higher energy levels. Using this phenomenon, a significant pressure-induced PH enhancement (PIPE) was observed for DBrBP-PI up to 0.9 GPa upon excitation at 365 nm, which is a rare phenomenon for organic polymers. This study indicates that even in colorless and optically transparent amorphous polymers, an enhancement of PH due to restricted molecular motion and intensified ISC outweighs the deactivation due to intermolecular energy transfer under certain pressures, leading to an increase in Φ PH .

While the dopaminergic system is important for cognitive processes, it is also sensitive to the influence of physical activity (PA). We summarize current evidence on whether PA-related changes in the human dopaminergic system are associated with alterations in cognitive performance, discuss recent advances, and highlight challenges and opportunities for future research., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Although many cross-sectional studies showed that psychotic experiences (PEs) and dissociation were closely related, the longitudinal association between them remains unknown. Therefore, the aim of the current study was to examine the longitudinal association of these two symptoms throughout adolescence, under the hypothesis that these two symptoms are bidirectionally associated. Data were obtained from a population-based cohort, the Tokyo Teen Cohort study (TTC; N = 3171). PEs and dissociation were assessed at 10, 12, 14, and 16 years of age. PEs were assessed using a total score from five-item self-report questionnaires derived from the Diagnostic Interview Schedule for Children (DISC-C). Dissociation was assessed using subscale scores of the Child Behavior Checklist (CBCL) completed by primary caregivers. We examined the longitudinal relationship between PEs and dissociation using the random intercept cross-lagged panel model (RI-CLPM). The within-person component of the RI-CLPM revealed no significant cross-lagged effect of dissociation on PEs at any time point. On the other hand, there was a significant (p < 0.05) association between PEs at age 14 and dissociation at age 16 (β = 0.106, 95 % CI 0.047-0.165). The between-person component revealed a significant time-invariant relationship between the two symptoms (β = 0.324, 95 % CI 0.239-0.410). The longitudinal relationship between PEs and dissociation was limited at the within-person level, whereas the between-person correlation was significant. The only significant longitudinal pathway was from PEs to dissociation, suggesting that PEs may be a predictor of dissociation in mid-adolescence., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Various driver mutations and the corresponding molecular-targeted drugs have been detected and developed in non-small cell lung cancer. There were many cases in which surgical specimens had happened to find double primary cancers. However, to our knowledge, our case was the first report of synchronous double primary lung adenocarcinomas harboring epidermal growth factor receptor ( EGFR ) L858R and mesenchymal-to-epithelial transition ( MET ) exon 14 skipping mutations. A 75-year-old Japanese woman with chronic heart and renal failures was referred to our department because of a growing nodule in the right upper lung field on chest X-ray films. Chest computed tomography (CT) detected a nodule in the right S 1 and another nodule in the left S 1+2 . Bronchoscopic biopsy diagnosed the right S 1 nodule as moderately differentiated adenocarcinoma. Oncomine Dx Target Test Multi-CDx system of the right S 1 adenocarcinoma detected EGFR L858R mutation. The 18 F -fluorodeoxyglucose positron emission tomography/CT showed abnormal uptakes both in the right S 1 and the left S 1+2 nodules, and in the bilateral inferior paratracheal lymph nodes. We made a diagnosis of c-stage IIIA (cT 1b N 2 M 0 ) of adenocarcinoma in the right S 1 and suspected another primary lung cancer in the left S 1+2 . Considering her general conditions, comorbidities and wishes, we started osimertinib. The right S 1 cancer achieved partial response (PR), while the left S 1+2 nodule and lymph nodes enlarged. Aspiration cytology from the left supraclavicular lymph node showed adenocarcinoma. The FoundationOne ® Liquid CDx tumor profiling test detected not only EGFR L858R, but also MET exon 14 skipping mutation. We made a diagnosis of another primary adenocarcinoma from the left S 1+2 nodule (cT 1b N 3 M 0 , c-stage IIIB) with MET mutation, and changed osimertinib to capmatinib. Although the left S 1+2 cancer achieved and maintained PR by capmatinib, the right S 1 cancer increased, and several new metastases appeared. The subsequent switch from capmatinib to osimertinib could not control cancers. In this case, we tried to switch monotherapies from osimertinib to capmatinib for double primary adenocarcinomas harboring different two driver mutations, according to each cancer progression. The temporal and spatial heterogeneity reinforces the need for primary tissue biopsy if dual primaries are suspected. Temporally distinct liquid biopsies, not standard at present, may be considered., Competing Interests: All authors have no conflict of interest to declare., (Copyright 2024, Ando et al.)

Background: Renal artery pseudoaneurysm (RAP) is one of the most stressful and life-threatening complications of partial nephrectomy, the standard treatment for small renal cell carcinoma. The use of a monopolar soft coagulation system for hemostasis during robot-assisted partial nephrectomy (RAPN) is expected to prevent post-surgical RAP development. In this study, we aimed to investigate how the use of a soft coagulation system in RAPN reduces postoperative pseudoaneurysms and changes renal function over time., Methods: The incidence of pseudoaneurysms and postoperative renal function were compared in 208 partial nephrectomies performed between May 2016 and March 2023 at a single institution, with propensity score matching to balance patient backgrounds. Outcomes were analyzed using multivariate logistic or linear regression analyses., Results: In total, 80 matched pairs were analyzed. One (1.2%) and eighteen (22.5%) pseudoaneurysms were found in the soft coagulation users and non-users, respectively (P<0.001). Compared to the non-user group, postoperative estimated glomerular filtration rates (eGFRs) in the user group were 89% vs. 96% (P<0.001), 87% vs. 93% (P=0.009), and 88% vs. 92% (P=0.15) at 1, 3, and 12 months, respectively. Subsequent multivariate analyses showed a lower incidence of pseudoaneurysms in the user group with an odds ratio of 0.05 [95% confidence interval (CI): 0.01 to 0.44; P=0.007], and no significant difference in the rate of change in renal function at 12 months postoperatively (-1.1%, 95% CI: -5.5% to 3.3%; P=0.61)., Conclusions: The use of a soft coagulation system reduces pseudoaneurysm occurrence after partial nephrectomy. Although renal function decreased in the short-term for the use group, no long-term differences were observed., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-84/coif). The authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)

Competing Interests: The authors have each completed and submitted an ICMJE form for Disclosure of Potential Conflicts of Interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. A. Ozaki reports receiving consulting fees from MNES Inc. and Becton, Dickinson and Company, as well as payments from Kyowa Kirin Inc., Taiho Pharmaceutical Co. Ltd., Pfizer Japan, and Daiichi Sankyo. I. Cho reports receiving consulting fees from MNES Inc. and Bionics Co. Ltd.

Correction of coagulation is a crucial aspect of trauma care. While there are reports highlighting the effectiveness of fibrinogen concentrate in severe trauma cases with coagulopathic complications, literature on its use in pediatric cases remains limited. This paper discusses the case of a 5-year-old male presenting with a splenic injury and associated coagulopathy. We administered fibrinogen concentrate to enhance his coagulability prior to performing transcatheter arterial embolization utilizing gelatin sponges, aiming for optimal hemostasis. Post-administration, the patient's fibrinogen levels improved significantly, leading to successful hemostasis and a positive clinical outcome., Competing Interests: 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., (© 2024 The Authors.)

We report the case of a traveler who returned from Zambia and was diagnosed with Mediterranean spotted fever (MSF), an infectious disease caused by Rickettsia conorii conorii. The patient presented to Sapporo City General Hospital with symptoms of fever, malaise, headache, and rash. The pathogen was identified by Polymerase Chain Reaction assays and subsequent analyses. The patient improved with 10-day treatment of oral doxycycline. Although some cases of MSF have been reported in sub-Saharan Africa, none have been reported in Zambia. Rhipicephalus sanguineus sensu lato, the vector of the Rickettsia conorii conorii, has been found in various areas of Zambia. Our case report highlights the potential threat of Mediterranean spotted fever in urban areas of Zambia., Competing Interests: Declaration of competing interest Yongjin Qiu is the recipient of the grant for research about tick and tick-borne pathogens in Zambia from Japan Agency for Medical Research and Development, and supported by Japan Society for the promotion of science., (Copyright © 2024. Published by Elsevier GmbH.)

Kampo medicine, a traditional Japanese herbal medicine, is covered by the Japanese National Health Insurance and prescribed for various purposes. While relatively safe with few adverse effects, it may potentially cause severe adverse effects, such as lung injury. Herein, we describe the case of a 61-year-old Japanese woman with choreito-induced lung injury that manifested as organizing pneumonia (OP) with diffuse alveolar hemorrhage (DAH). She was referred to our department due to multiple abnormal opacities detected on annual chest radiography. Chest computed tomography (CT) revealed multiple nodules in bilateral lungs. Bloody bronchoalveolar lavage fluid was obtained from the left lingular lobe, appearing nearly normal, while a transbronchial lung biopsy from a subpleural nodule in the left lower lobe was pathologically consistent with OP. The drug lymphocyte stimulation test result was positive for choreito, which the patient had regularly consumed for 6 - 7 months to treat hematuria. Consequently, a diagnosis of choreito-induced OP and DAH was made. Owing to the discontinuation of choreito alone and without the introduction of systemic steroid therapy, the multiple nodules shrank and eventually disappeared on follow-up chest CT. Regardless of the type of crude drug used in Kampo medicine, clinicians must always be careful for potential lung injury, which may present as OP with DAH., Competing Interests: The authors declare that they have no conflict of interest., (Copyright 2024, Ando et al.)

Objective: Postexercise vagal dysfunction is linked to noncardiovascular mortality in hemodialysis patients, but the mechanism is unknown. This study aimed to determine the association of cardiovagal neuropathy with systemic inflammation, protein-energy wasting, and noncardiovascular hospitalization., Methods: This 2-center retrospective cohort study analyzed data from 280 hemodialysis patients who underwent exercise test. Patients were assessed for heart rate (HR) recovery (bpm) for 1 minute after exercise, a marker of vagal function, and were divided into 3 categories (Low: ≤ 6, Mid: 7-11, High: ≥ 12 bpm). We followed 1-year changes in the systemic inflammation-based prognostic score (Glasgow Prognostic Score [GPS]), body weight, and creatinine generation rate (CGR), an indicator of muscle mass, as well as 2-year hospitalization., Results: The HR recovery category was associated with serum C-reactive protein and albumin levels and GPS. After 1 year, the low HR recovery category was associated with worsening in GPS (low, 0 [0-0.5]; mid, 0 [0-1]; high, 0 [0-0]), weight (low, 100.0 [96.1-102.5]; mid, 101.3 [98.9-105.0]; high, 100.5 [98.2-102.9]%), and CGR (low, 97.0 [88.5-111.4]; mid, 110.2 [90.9-124.8]; high, 106.2 [95.5-115.5]%), and the correlations with GPS and CGR remained consistent after adjusting for confounders such as exercise capacity and hospitalization during the follow-up period. There were 117 patients hospitalized. Compared to the high HR recovery category, the mid (hazard ratio: 1.8, 95% confidence interval [CI]: 1.1-3.1, P = .02) and low (hazard ratio: 2.4, 95% CI: 1.5-4.0, P = .001) categories were independently associated with an increased risk of all-cause hospitalization. For noncardiovascular disease hospitalization, the low HR recovery category was independently associated with increased risk of hospitalization (hazard ratio: 2.1, 95% CI: 1.2-3.7, P = .007)., Conclusions: Vagal neuropathy in this population can contribute to adverse outcomes associated with systemic inflammation and protein-energy wasting., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

A 72-year-old man with diffuse large B-cell lymphoma underwent fluorine-18 fluorodeoxyglucose (FDG) PET/CT, revealing lymphoma lesions and no evidence of aortitis. The patient received chemotherapy and was treated with granulocyte colony-stimulating factor (G-CSF) for neutropenia. During chemotherapy, the patient underwent PET/CT again, revealing FDG accumulation and wall thickening at the aortic arch, which suggested aortitis. The patient was only experiencing fatigue. G-CSF-associated aortitis was suspected, and the original G-CSF was switched to another G-CSF while continuing chemotherapy. Three months later, the third round of PET/CT showed that FDG accumulation and wall thickening of the aortic arch vanished. PET/CT may be useful for not only the diagnosis but follow-up of G-CSF-associated aortitis. Radiologists should recognize incidental aortitis on PET/CT in patients receiving G-CSF administration., (© 2024 The Authors.)

Background and Hypothesis: Problematic internet use (PIU) is prevalent among adolescents. Past research suggested cross-sectional associations between PIU and psychotic experiences, but little information is available on the longitudinal association. We hypothesized that PIU in adolescence may be longitudinally associated with psychotic experiences, adjusting for confounders., Study Design: We analyzed a random sample of adolescents in the Tokyo Teen Cohort to examine how PIU at ages 10 (2012-2015), 12 (2014-2017), and 16 (2019-2021) was associated with mental health issues at age 16. PIU was evaluated by the modified Compulsive Internet Use Scale, psychotic experiences by the Adolescent Psychotic-like Symptom Screener, and depression by the Short Mood and Feelings Questionnaire. We also examined the mediating role of social withdrawal., Study Results: We analyzed 3171 adolescents; 151 reported psychotic experiences and 327 reported depression at age 16. Compared with the lowest tertile PIU group, the highest tertile PIU group at age 12 showed an increased adjusted risk of psychotic experiences (RD 3.3%, 95% CI 2.9%-3.7%; RR 1.65, 95% CI 1.55-1.73) and depression (RD 5.9%, 95% CI 5.5%-6.3%; RR 1.61, 95% CI 1.55-1.68) at age 16. PIU at age 16 showed analogous results, while PIU at age 10 suggested a smaller impact. Social withdrawal mediated 9.4%-29.0% of the association between PIU and psychotic experiences., Conclusions: PIU is longitudinally associated with psychotic experiences and depression in adolescents. Further longitudinal and intervention studies are warranted to provide robust public health implications and foster a safer digital future., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background/aim: In East Asia, the standard treatment for resectable advanced gastric cancer involves gastrectomy and postoperative adjuvant chemotherapy; nevertheless, neoadjuvant chemotherapy is also expected to improve survival rates. However, it remains unclear whether the same criteria can be used to select adjuvant chemotherapy for patients treated with neoadjuvant chemotherapy, or how survival varies between post-chemotherapy pathological Stage (ypStage) and pathological Stage without chemotherapy (pStage). This study evaluated the long-term outcomes of ypStage and pStage in gastric cancers and investigated the optimal intensity of adjuvant chemotherapy for patients who have received preoperative chemotherapy., Patients and Methods: From January 2007 to November 2019, 1,585 patients underwent radical gastrectomy for gastric cancer at the Kanagawa Cancer Center. The patient background was adjusted by propensity score matching, and recurrence-free survival was compared between the two groups. In addition, a prognostic factor analysis was conducted for each yp/pStage., Results: The 5-year recurrence-free survival rates for yp/pStage I were 77.1% and 90.9%, respectively, with no significant difference (p=0.342). The 5-year recurrence-free survival rates for yp/pStage II were 50.4% and 69.1%, respectively, with no significant difference (p=0.062). The 5-year recurrence-free survival rates for yp/pStage III were 42.9% and 68.7%, respectively, with a significant difference observed (p=0.016). In the prognostic factor analysis for each stage, the presence or absence of preoperative chemotherapy was selected as an independent prognostic factor for yp/pStage I [hazard ratio (HR)=17.72; p=0.001] and yp/pStage II (HR=2.655, p=0.003)., Conclusion: ypStage tends to have a worse prognosis than pStage, and further development of multidisciplinary treatment is necessary., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The purpose of this study was to clarify the temporal coordination between gaze, head, and arm movements during forehand rallies in table tennis. Collegiate male table tennis players (n = 7) conducted forehand rallies at a constant tempo (100, 120, and 150 bpm) using a metronome. In each tempo condition, participants performed 30 strokes (a total of 90 strokes). Gaze, head, and dominant arm (shoulder, elbow, and wrist) movements were recorded with an eye-tracking device equipped with a Gyro sensor and a 3-D motion capture system. The results showed that the effect of head movements relative to gaze movements was significantly higher than that of eye movements in the three tempo conditions. Our results indicate that head movements are closely associated with gaze movements during rallies. Furthermore, cross-correlation coefficients (CCs) between head and arm movements were more than 0.96 (maximum coefficient: 0.99). In addition, head and arm movements were synchronized during rallies. Finally, CCs between gaze and arm movements were more than 0.74 (maximum coefficient: 0.99), indicating that gaze movements are temporally coordinated with arm movements. Taken together, head movements could play important roles not only in gaze tracking but also in the temporal coordination with arm movements during table tennis forehand rallies., (© 2024 The Authors. European Journal of Sport Science published by Wiley‐VCH GmbH on behalf of European College of Sport Science.)

Background: Understanding the etiology of psychosis is essential to the development of preventive interventions. The COVID-19 pandemic provides a rare natural experiment that can expand our understanding of the role of social factors in the trajectories and etiology of psychosis across adolescence, particularly in Tokyo where the prevalence of actual COVID-19 infection remained low. We hypothesized that the likelihood of self-reporting psychotic experiences (PEs) would increase following the onset of the COVID-19 pandemic., Methods: The Tokyo Teen Cohort (TTC) is a prospective cohort study of adolescents in the general population of the Tokyo metropolitan area, followed from age 10 to 16 years. We used multi-level linear regression models to test the associations between the phase of the COVID-19 pandemic and self-reported PEs., Results: Among 1935 adolescents included in the analysis, a rapid increase in PEs occurred at the onset of the COVID-19 pandemic, following approximately 6 years of steady decline across prior waves. This association was more pronounced for boys compared to girls. This increase became more pronounced as the pandemic moved into later phases, defined based on contemporaneous sociopolitical changes in Tokyo (i.e. changes to school closure, social distancing guidelines, and the state of emergency status)., Conclusions: The steady decline in PEs across adolescence was halted and reversed concurrent with the COVID-19 pandemic onset, despite very low rates of COVID-19 infection. This implicates COVID-19 related socioenvironmental factors as contributory etiological factors in the development of PEs in this adolescent cohort., (© 2023 Association for Child and Adolescent Mental Health.)

Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3'-5' DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause DNA damage. Here, we show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and that cells expressing RVCL mutant TREX1 are more vulnerable to DNA damage induced by chemotherapy and cytokines that up-regulate TREX1, leading to depletion of TREX1-high cells in RVCL mice. RVCL-associated TREX1 mutants inhibit homology-directed repair (HDR), causing DNA deletions and vulnerablility to PARP inhibitors. In women with RVCL, we observe early-onset breast cancer, similar to patients with BRCA1/2 variants. Our results provide a mechanistic basis linking aberrant TREX1 activity to the DNA damage theory of aging, premature senescence, and microvascular disease., (© 2024. The Author(s).)

Aim: The efficacy of titratable fixed-ratio combination therapy by a combination preparation of insulin degludec and liraglutide (IDegLira) in Japanese patients with type 2 diabetes, focusing particularly on the change in Fibrosis-4 index (FIB-4), a noninvasive method for the evaluation of liver fibrosis, was investigated., Methods: As the full analysis set, 113 patients were treated with IDegLira. The patients were categorized into two groups according to the absence (GLP-1RA-naïve group, n = 72) or presence (GLP-1RA-treated group, n = 41) of glucagon-like peptide-1 receptor agonist (GLP-1RA) use before starting IDegLira. The clinical parameters were retrospectively determined over 6 months., Results: The glycated hemoglobin value was significantly reduced in both groups. The bodyweight significantly decreased from 67.4 ± 11.0 kg at baseline to 66.4 ± 11.6 kg at 6 months in the GLP-1RA-naïve group, although it slightly increased in the GLP-1RA-treated group. FIB-4 significantly decreased from 1.60 ± 0.84 at baseline to 1.49 ± 0.74 at 6 months in the GLP-1RA-naïve group. Although FIB-4 significantly increased in the GLP-1RA-treated group, it remained within the low-risk level for liver fibrosis., Conclusion: Fixed-ratio combination therapy using IDegLira for the treatment of type 2 diabetes is useful for glycemic control and weight management. In particular, IDegLira may be more effective for lowering FIB-4 than adding unused oral antidiabetic agents or increasing the dose of insulin in GLP-1RA-naïve patients., (© 2023 Japan Society of Hepatology.)

Introduction: ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not., Research Design and Methods: Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year., Results: The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR., Conclusions: Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD., Trial Registration Number: UMIN000011525., Competing Interests: Competing interests: JW receives speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Kyowa Kirin, Novo Nordisk, and Mitsubishi Tanabe, and receives grant support from Bayer, Chugai, Kyowa Kirin, Otsuka, Shionogi, Sumitomo, and Mitsubishi Tanabe., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The photoluminescence (PL) properties of four types of blue fluorescent semi-aliphatic polyimides (PIs) derived from aromatic dianhydrides (ODPA, BPDA, HQDEA, and BPADA) and an alicyclic diamine (DCHM) were investigated at temperatures ranging from room temperature (RT, 298 K) to 30 K to analyse the origins of their non-radiative relaxation (NR) processes. These PIs exhibited significant increases in fluorescence (FL) intensity and lifetimes when lowering the temperature, stabilising below 100 K. The PIs containing ether (-O-) linkages showed a shoulder peak at around 500 nm below 150 K, which is attributable to phosphorescence (PH). These results show that the NR deactivation at RT includes three processes: intersystem crossing (ISC) from the excited singlet (S 1 ) to the triplet (T 1 ) state, temperature-dependent NR from the S 1 state, which becomes suppressed below around 100 K, and temperature-independent NR. Based on the analyses of the temperature dependences, polymer structures, and quantum chemical analysis of molecular orbitals, we contemplate that the temperature-dependent NR is attributable to the excitation quenching by defect states mediated by excitation migration, and the temperature-independent NR may be caused by the deactivation of the excited state induced by molecular vibrations.

The purpose of this study was to investigate whether a combination of electrical muscle stimulation (EMS) and cycling exercise is beneficial for improving cognitive performance. Eighteen participants (7 females and 11 males) performed a Go/No-Go task before and 2 min after i) cycling exercise (EX), ii) a combination of EMS and cycling (EMS + EX) and iii) a control (rest) intervention in a randomized controlled crossover design. In the EX intervention, the participants cycled an ergometer for 20 min with their heart rate maintained at ∼120 beats·min -1 . In the EMS + EX intervention, the participants cycled an ergometer simultaneously with EMS for 20 min, with heart rate maintained at ∼120 beats·min -1 . In the Control intervention, the participants remained at rest while seated on the ergometer. Cognitive performance was assessed by reaction time (RT) and accuracy. There was a significant interaction between intervention and time ( p = 0.007). RT was reduced in the EX intervention ( p = 0.054, matched rank biserial correlation coefficient = 0.520). In the EMS + EX intervention, RT was not altered ( p = 0.243, Cohen's d = 0.285) despite no differences in heart rate between the EX and EMS + EX interventions ( p = 0.551). RT was increased in the Control intervention ( p = 0.038, Cohen's d = -0.529). These results indicate that combining EMS and cycling does not alter cognitive performance despite elevated heart rate, equivalent to a moderate intensity. The present findings suggest that brain activity during EMS with cycling exercise may be insufficient to improve cognitive performance when compared to exercise alone., 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 Ando, Ishioka, Kambayashi, Kano, Fujibayashi, Costello and Sudo.)

Orthognathic surgery may induce hemorrhage resulting from nasal mucosal injury or from maxillary osteotomy sites, and if severe, the hemorrhage may cause airway obstruction. The patient in this case report was a 27-year-old woman who underwent Le Fort I and bilateral sagittal split osteotomies under general anesthesia. There were no abnormal intraoperative vital signs. However, immediately after the patient was returned to the ward, significant bleeding that required frequent suctioning was observed in the oral cavity. As the bleeding persisted, the surgeon attempted to insert epinephrine-soaked gauze and polyvinyl acetal sponges into both nasal cavities, but hemostasis was difficult to obtain. To achieve hemostasis by compression/closure at the choana and maintain nasal patency, we inserted a modified cuffed endotracheal tube to serve as a transnasal airway and a choanal hemostatic balloon. This method resulted in hemostasis. The volume of blood loss after returning to the ward was approximately 420 mL. The transnasal airway and choanal balloon was useful for airway management and the prevention of intranasal bleeding into the lower pharyngeal regions. Furthermore, the method was simple and minimally invasive, suggesting its clinical usefulness in similar situations.

Protein phosphatase 2A (PP2A) is an essential serine/threonine protein phosphatase, and its dysfunction is involved in the onset of cancer and neurodegenerative disorders. PP2A functions as a trimeric holoenzyme whose composition is regulated by the methyl-esterification (methylation) of the PP2A catalytic subunit (PP2Ac). Protein phosphatase methylesterase-1 (PME-1) is the sole PP2Ac methylesterase, and the higher PME-1 expression is observed in various cancer and neurodegenerative diseases. Apart from serving as a methylesterase, PME-1 acts as a PP2A inhibitory protein, binding directly to PP2Ac and suppressing its activity. The intricate function of PME-1 hinders drug development by targeting the PME-1/PP2Ac axis. This study applied the NanoBiT system, a bioluminescence-based protein interaction assay, to elucidate the molecular mechanism that modulates unknown PME-1/PP2Ac protein-protein interaction (PPI). Compound screening identified that the CHK1 inhibitors inhibited PME-1/PP2Ac association without affecting PP2Ac methylation levels. CHK1 directly phosphorylates PP2Ac to promote PME-1 association. Phospho-mass spectrometry identified multiple phospho-sites on PP2Ac, including the Thr219, that affect PME-1 interaction. An anti-phospho-Thr219 PP2Ac antibody was generated and showed that CHK1 regulates the phosphorylation levels of this site in cells. On the contrary, in vitro phosphatase assay showed that CHK1 is the substrate of PP2A, and PME-1 hindered PP2A-mediated dephosphorylation of CHK1. Our data provides novel insights into the molecular mechanisms governing the PME-1/PP2Ac PPI and the triad relationship between PP2A, PME-1, and CHK1., Competing Interests: Conflict of 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 Inc. All rights reserved.)

Objectives: We investigated the correlation between surgical outcomes and postoperative urinary continence recovery in robot-assisted radical prostatectomy (RARP)., Methods: Patients who underwent RARP in our institution (n = 195) were included in this study. Preserved urethral length (PUL) was assessed during the procedure. Other outcomes of the surgical procedure were collected from operative records. Kaplan-Meier analysis with log-rank test was used to compare urinary continence recovery rate with the PUL, sparing of the neurovascular bundle (NVB), and other surgical procedures. Univariate and multivariate analyses were performed using Cox proportional hazards model, and p-values of <0.05 were considered significant., Results: Patients with a PUL ≥26 mm had 10.0%, 24.7%, 36.6%, and 89.0% continence recovery rates at 30, 60, 90, and 365 days after surgery, respectively, while patients with a PUL <26 mm had 0%, 17.8%, 26.1%, and 80.9% recovery rates, respectively. Kaplan-Meier curves showed significantly better postoperative urinary continence recovery at 30 days after RARP in patients with a PUL ≥26 mm than those with a PUL <26 mm (p = 0.0028) and in patients with NVB preservation than those with no NVB preservation (p = 0.014). Urinary continence recovery within 30, 60, and 90 days after surgery was 90.6% for patients with a PUL of ≥26 mm and NVB preservation, while only 82.3% for patients with a PUL of <26 mm or no NVB preservation., Conclusion: Our results suggest that a PUL ≥26 mm and NVB preservation after RARP correlate with a significantly higher postoperative rate of recovery of urinary continence., (© 2024 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

Objective: Evidence on the impact of the COVID-19 pandemic on adolescent mental health is mixed and does not disentangle natural age-related changes. We compared depressive symptoms among 16-year-olds surveyed, at a fourth wave, before or during the pandemic, while accounting for expected trajectories of within-person change based on 3 prior waves., Method: In this longitudinal cohort of 3,171 adolescents in Tokyo, Japan, adolescents were grouped based on their age 16 survey timing: pre-pandemic (February 2019 to February 2020) and during-pandemic (March 2020 to September 2021). Depressive symptoms were self-reported using the Short Mood and Feelings Questionnaire. Mixed-effect models were fitted to assess group differences while controlling for previous trends. Variations by sex, household income, and pandemic phase (early, late first-year, and second-year) were examined., Results: Of 2,034 eligible adolescents, 960 (455 girls) were assessed before and 1,074 (515 girls) during the pandemic. Overall, depressive symptoms increased by 0.80 points (95% CI 0.28-1.31, 0.15 SD of the population average). This increase varied by sex and pandemic phase. For boys the increase emerged in the late first-year phase and enlarged in the second-year phase (mean difference from pre-pandemic: 1.69, 0.14-3.24), whereas for girls it decreased in the early school-closure phase (mean difference: -1.98, -3.54 to -0.41) and returned to the pre-pandemic level thereafter, with no additional increases during the pandemic., Conclusion: Into the second year of the COVID-19 pandemic, depressive symptoms of 16-year-olds worsened above the expected age-related change only in boys. Continuous monitoring and preventive approaches for adolescents at the population level are warranted., Diversity & Inclusion Statement: We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex and gender balance in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

A 67-year-old man with type 1 diabetes, Cronkhite-Canada syndrome, and membranous nephropathy who received insulin therapy was admitted to our hospital with right hemiplegia and dysarthria. Brain magnetic resonance imaging revealed a lesion with a high diffusion-weighted imaging signal and low apparent diffusion coefficient signal in the posterior limb of the left internal capsule. He was hypoglycemic with a blood glucose level of 56 mg/dL (3.1 mmol/L). Following glucose administration, the patient's symptoms resolved within several hours. The patient experienced similar transient hypoglycemic hemiplegia at midnight, three times within 10 days. In a literature review of 170 cases of hypoglycemic hemiplegia, 26 cases of recurrent hemiplegia were investigated. Recurrent hypoglycemic hemiplegia occurs more frequently on the right side than on the left side, and most recurrences occur within approximately a week, almost exclusively at midnight and in the early morning. We speculate that hypoglycemia-associated autonomic failure may be involved in the nocturnal recurrence of episodes. In our patient, depleted endogenous insulin secretion and lipodystrophy at the injection site, may have acted as additional factors, leading to severe hypoglycemia despite the absence of apparent autonomic neuropathy. Clinically, it is important to recognize hypoglycemia as a cause of hemiplegia to avoid unnecessary intervention and to maintain an appropriate blood glucose level at midnight and early in the morning to prevent recurrent hypoglycemic hemiplegia.

Background: Scrub typhus (ST) is endemic in Fukushima, with the largest number of cases reported in Japan from 2009 to 2010. Although ST is highly treatable, its atypical clinical presentation impedes diagnosis, causing delays in treatment., Methods: We review the clinical features of ST in adults from 2008 to 2017 at Ohta Nishinouchi General Hospital in Fukushima, Japan., Results: Fifty-five cases (serotype Karp 24, Irie/Kawasaki 21, Hirano/Kuroki 10) of ST were confirmed via serology based on elevated immunoglobulin (Ig)M and IgG and polymerase chain reaction positivity of eschar samples. The mean age was 69 years, and 64% were female. The case fatality rate was 1.8% (1/55). Approximately 70% of cases (38/55) were not diagnosed as ST upon the initial clinic visit. Inappropriate use of antibiotics was identified in 22% of cases (12/55). In terms of atypical clinical features, 1 or more of the manifestations, fever, rash, and eschar, was absent in 31% of cases (17/55). Approximately 11% of cases presented without eschar (6/55; Karp 1, Irie/Kawasaki 1, Hirano/Kuroki 4). Moreover, severe complications were observed with shock and disseminated intravascular coagulation in 7% of cases (4/55), Thus, while 53% of cases presented with the typical triad (29/55), unusual complications and atypical features occurred in 40% (22/55)., Conclusions: Diagnosis of ST becomes clinically challenging in the absence of typical features. In Fukushima, an endemic area of ST, an atypical presentation involving multisystem disease is common., Competing Interests: Potential conflicts of interest. All authors have no funding or conflicts of interest to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Langerhans cell histiocytosis is a rare neoplastic disorder characterized by the proliferation of Langerhans cells and often accompanied by eosinophil infiltration. Charcot-Leyden crystals, composed of galectin 10, are occasionally observed in Langerhans cell histiocytosis; however, histological images are rarely reported. We herein present a patient with Langerhans cell histiocytosis with Charcot-Leyden crystals and hexagonal crystals by describing the histologic and immunohistochemical features of a lymph node. A unique distribution of Charcot-Leyden crystals and hexagonal crystals was observed in this patient, shedding light on their possible formation process of the latter. We discuss the biological significance of eosinophilic abscesses in Langerhans cell histiocytosis and propose that these crystals may be linked to extracellular trap-cell death (ETosis). This example challenges the conventional characterization of "necrosis" in Langerhans cell histiocytosis and underscores the importance of recognizing ETosis as a potential mechanism involved in the pathogenesis of Langerhans cell histiocytosis. Further studies are underway to validate significance of these findings in a larger cohort of Langerhans cell histiocytosis patients., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Macronutrient intake can be one of the most influential factors in cognitive and neural development in adolescents. Adolescence is a specific period of cognitive and neural development, and nutritional effects during this period could be life-long. Therefore, understanding the effects of macronutrient intake on cognitive and neural development in adolescents is crucially important. We thus examined the association across macronutrient intake, intelligence, and neural development using population-based cohort data., Methods: We conducted two studies. In study 1, we included a total of 1,734 participants (boys, 907, age [mean ± standard deviation] 171.9 ± 3.44 months; range 163.0-186.0 months) from the Tokyo TEEN Cohort (TTC) to examine the association between macronutrient intake and intelligence quotient (IQ). In study 2, we included a total of 63 participants (boys, 38, age 174.4 ± 7.7 months; range 160.7-191.6 months) to investigate the effect of nutrition intake on neural development using graph theory analysis for resting-state functional magnetic resonance imaging (rs-fMRI) derived from a subset of the TTC., Results: TTC data revealed that a higher IQ was associated in boys with increased protein intake ( β  = 0.068, p  = 0.031), and in girls, with reduced carbohydrate intake ( β  = -0.076, p  = 0.024). Graph theory analysis for rs-fMRI at approximately age 12 has shown that impaired local efficiency in the left inferior frontal gyrus was associated with higher carbohydrate and fat intake ([x, y, z] = [-51, 23, 8], p FDR-corrected  = 0.00018 and 0.02290, respectively), whereas increased betweenness centrality in the left middle temporal gyrus was associated with higher carbohydrate, fat, and protein intake ([x, y, z] = [-61, -43, -13], p FDR-corrected  = 0.0027, 0.0029, and 0.00075, respectively). Moreover, we identified a significant moderating effect of fat and protein intake on the relationship between change in betweenness centrality over a 2-year measurement gap in the left middle temporal gyrus and intelligence ( β  = 12.41, p  = 0.0457; β  = 12.12, p  = 0.0401, respectively)., Conclusion: Our study showed the association between macronutrient intake and neural development related to intelligence in early adolescents. Appropriate nutritional intake would be a key factor for healthy cognitive and neural development., 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 Nakamura, Yamasaki, Okada, Ando, Nishida, Kasai and Koike.)

Objectives: To compare the incidence of surgical site infections (SSI) between robot-assisted and open radical cystectomies and investigate the risk factors for SSI after radical cystectomies., Methods: Consecutive patients who underwent radical cystectomy between July 2008 and December 2022 were retrospectively reviewed. The prevalence and characteristics of SSI after open and robot-assisted radical cystectomies were compared, and the risk factors for SSI were investigated using propensity score matching., Results: This study enrolled 231 patients (open: 145, robot-assisted: 86). In the robot-assisted group, urinary diversion was performed using an intracorporeal approach. SSI occurred in 34 (open: 28, robot-assisted: 6) patients, and the incidence was significantly lower in the robot-assisted group (19.3% vs. 7.0%, p = 0.007). After propensity score matching cohort (open: 34, robot-assisted: 34), increased bleeding volume, blood transfusion, and delayed postoperative oral feeding were significantly associated with SSI. Only increased bleeding volume remained a significant risk factor in the multivariate regression analysis (odds ratio, 1.13 [per 100 mL increase]; 95% confidence interval: 1.02-1.25; p = 0.001). The cutoff bleeding volume for predicting SSI was 1630 mL with an area under the receiver operating characteristic curve, sensitivity, and specificity of 0.773, 0.73, and 0.75, respectively., Conclusions: The incidence of SSI after robot-assisted radical cystectomy was significantly lower than that after the open procedure. However, decreased bleeding volume, which was significantly associated with robot-assisted procedures, was an independent and more significant factor for reducing SSI after radical cystectomy than the differences of the surgical procedure even after propensity score matching., (© 2024 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)