Development of a dose-rate dosimeter using a silicon photodiode for a medical linear accelerator in a 10 MV flattening filter-free mode.

This study was aimed at developing a dose-rate dosimeter to measure the instantaneous dose rate of a commercially available medical linear accelerator. A dose-rate dosimeter composed of a silicon photodiode (Si-PD), a complementary metal-oxide semiconductor single operational amplifier, a resistor of 20 MΩ, a capacitor of 100 pF, and a mini-substrate measuring 16 × 16 mm2 was evaluated. Voltage outputs from the proposed dosimeter were measured using an analog-to-digital converter on a microcomputer. A custom-made x-ray tube generator at an energy of 120 kV with a tube current ranging from 0.1 to 2.0 mA was used for the dose-rate calibration. Dose-rate calibration was performed 83.3 mm from an x-ray source using a commercially available semiconductor dosimeter. The developed Si-PD dosimeter could measure up to 0.6 Gy/s at a distance of 19.3 mm from the x-ray source. Measurements were also performed using a medical linear accelerator in a 10 MV flattening filter-free mode at depths of 0, 25, 50, and 100 mm with an irradiation field of 100 × 100 mm2 at a constant distance of 1000 mm from the source to the dosimeter. A peak voltage variation corresponding to the instantaneous dose rate was observed using a sampling period of 1.0 ms, and the peak voltages decreased with the depth. The detected pulse numbers were 512, 484, 491, and 511 at depths of 0, 25, 50, and 100 mm, respectively.

Longitudinal associations between subjective cognitive impairment, pain and depressive symptoms in home-dwelling older adults: Modelling within-person effects.

OBJECTIVES: Cognitive impairment, pain and depressive symptoms are common and interrelated factors in older adults. However, the directionality and specificity of their association remains unclarified. This study explored whether these factors prospectively increase reciprocal risk and examined the longitudinal association between these factors and quality of life (QoL). METHODS: This study used longitudinal data from The Older Persons and Informal Caregivers Survey Minimal Data Set (TOPICS-MDS; the Netherlands). Older adults self-reported cognitive impairment, pain, depressive symptoms and QoL at baseline and after 6 and 12 months of follow-up. The Random Intercept Cross-Lagged Panel Model was used to assess the prospective association between the three factors, while a multilevel linear regression analysis in a two-level random intercept model was used to examine the longitudinal associations between the three factors and QoL at the within-person level. RESULTS: The data of 11,582 home-dwelling older adults with or without subjective cognitive impairment were analysed. At the within-person level, pain at 6 months was associated with subsequent depressive symptoms (ß = 0.04, p = 0.024). The reverse association from depression to pain, and longitudinal associations between pain and subjective cognitive impairment and between depressive symptoms and subjective cognitive impairment were non-significant. Pain, depressive symptoms and subjective cognitive impairment showed a significant association with poor QoL 6 months later. CONCLUSIONS: A directional relationship was observed from pain to depressive symptoms. Pain reduction holds a potential benefit in the prevention of depressive symptoms, ultimately optimising the QoL of older adults.

Development of ZTA (80% Al2O3/20% ZrO2) pre-sintered blocks for milling in CAD/CAM systems.

The present work aims to develop a production method of pre-sintered zirconia-toughened-alumina (ZTA) composite blocks for machining in a computer-aided design and computer-aided manufacturing (CAD-CAM) system. The ZTA composite comprised of 80% Al2O3 and 20% ZrO2 was synthesized, uniaxially and isostatically pressed to generate machinable CAD-CAM blocks. Fourteen green-body blocks were prepared and pre-sintered at 1000 °C. After cooling and holder gluing, a stereolithography (STL) file was designed and uploaded to manufacture disk-shaped specimens projected to comply with ISO 6872:2015. Seventy specimens were produced through machining of the blocks, samples were sintered at 1600 °C and two-sided polished. Half of the samples were subjected to accelerated autoclave hydrothermal aging (20h at 134 °C and 2.2 bar). Immediate and aged samples were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Optical and mechanical properties were assessed by reflectance tests and by biaxial flexural strength test, Vickers indentation and fracture toughness, respectively. Samples produced by machining presented high density and smooth surfaces at SEM evaluation with few microstructural defects. XRD evaluation depicted characteristic peaks of alpha alumina and tetragonal zirconia and autoclave aging had no effect on the crystalline spectra of the composite. Optical and mechanical evaluations demonstrated a high masking ability for the composite and a characteristic strength of 464 MPa and Weibull modulus of 17, with no significant alterations after aging. The milled composite exhibited a hardness of 17.61 GPa and fracture toughness of 5.63 MPa m1/2, which remained unaltered after aging. The synthesis of ZTA blocks for CAD-CAM was successful and allowed for the milling of disk-shaped specimens using the grinding method of the CAD-CAM system. ZTA composite properties were unaffected by hydrothermal autoclave aging and present a promising alternative for the manufacture of infrastructures of fixed dental prostheses.

Comparison of mirabegron and vibegron for clinical efficacy and safety in female patients with overactive bladder: a multicenter prospective randomized crossover trial.

PURPOSE: To compare the efficacy and safety of mirabegron and vibegron in female OAB patients. METHODS: We conducted a multicenter, prospective, randomized crossover study of female patients with OAB. The patients were assigned to Group MV (mirabegron for 8 weeks, followed by vibegron for 8 weeks) or group VM (vibegron for 8 weeks, followed by mirabegron for 8 weeks). The primary endpoint was the change in OABSS from baseline, and the secondary endpoint was the change in FVC parameters. After completion of the study, each patient was asked which drug was preferable. RESULTS: A total of 83 patients were enrolled (40 and 43 in groups MV and VM, respectively). At 8th and 16th week, 33 and 29 in Group MV and 34 and 27 in Group VM continued to receive the treatment. The change in PVR was not significantly different between treatment with mirabegron and vibegron. The changes in OABSS, nighttime frequency, mean, and maximum voided volume were similar between mirabegron and vibegron. The mean change in the daytime frequency was greater in the vibegron than in the mirabegron. Of the 56 patients, 15 (27%) and 30 (53%) preferred mirabegron and vibegron, respectively. The remaining 11 patients (20%) showed no preference. The change in the urgency incontinence score during vibegron was better in patients who preferred vibegron to mirabegron. CONCLUSION: The efficacies of mirabegron and vibegron in female patients was similar. The patients' preference for vibegron could depend on the efficacy of vibegron for urgency incontinence.

Cytoprotective role of human dental pulp stem cell-conditioned medium in chemotherapy-induced alopecia.

BACKGROUND: Chemotherapy-induced alopecia (CIA) is a distressing adverse effect of chemotherapy, with an estimated incidence of 65% and limited treatment options. Cyclophosphamide (CYP) is a common alopecia-inducing chemotherapy agent. Human dental pulp stem cells (DPSCs) secrete several paracrine factors that up-regulate hair growth. Conditioned medium (CM) collected from DPSCs (DPSC-CM) promotes hair growth; culturing mesenchymal stem cells under hypoxic conditions can enhance this effect. METHODS: The effect of DPSC-CM cultured under normoxic (N-) and hypoxic (H-) conditions against CYP-mediated cytotoxicity in keratinocytes was examined using cell viability assay, lactate dehydrogenase (LDH) cytotoxicity assay, and apoptosis detection. The damage-response pathway was determined in a well-established CIA mouse model by analyzing macroscopic effects, histology, and apoptosis. Reverse transcription-quantitative PCR and Caspase-3/7 activity assay were used to investigate the impact of DPSC-CM on the molecular damage-response pathways in CYP-treated mice. The effect of post-CIA DPSC-CM application on post-CIA hair regrowth was analyzed by macroscopic effects and microstructure observation of the hair surface. Furthermore, to investigate the safety of DPSC-CM as a viable treatment option, the effect of DPSC-CM on carcinoma cell lines was examined by cell viability assay and a subcutaneous tumor model. RESULTS: In the cell viability assay, DPSC-CM was observed to increase the number of keratinocytes over varying CYP concentrations. Furthermore, it reduced the LDH activity level and suppressed apoptosis in CYP-treated keratinocytes. DPSC-CM exhibited the cytoprotective role in vivo via the dystrophic anagen damage-response pathway. While both N-CM and H-CM downregulated the Caspase-3/7 activity level, H-CM downregulated Caspase-3 mRNA expression. The proportion of post-CIA H-CM-treated mice with > 90% normal hair was nearly twice that of vehicle- or N-CM-treated mice between days 50 and 59 post-depilation, suggesting that post-CIA H-CM application may accelerate hair regrowth and improve hair quality. Furthermore, DPSC-CM suppressed proliferation in vitro in certain carcinoma cell lines and did not promote the squamous cell carcinoma (SCC-VII) tumor growth rate in mice. CONCLUSIONS: The potentiality of DPSC-CM and H-CM as a promising cytoprotective agent and hair regrowth stimulant, respectively, for CIA needs in-depth exploration.

GRP78 Contributes to the Beneficial Effects of SGLT2 Inhibitor on Proximal Tubular Cells in DKD.

The beneficial effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on kidney function are well-known; however, their molecular mechanisms are not fully understood. We focused on 78-kDa glucose-regulated protein (GRP78) and its interaction with SGLT2 and integrin-ß1 beyond the chaperone property of GRP78. In streptozotocin (STZ)-induced diabetic mouse kidneys, GRP78, SGLT2, and integrin-ß1 increased in the plasma membrane fraction, while they were suppressed by canagliflozin. The altered subcellular localization of GRP78/integrin-ß1 in STZ mice promoted epithelial mesenchymal transition (EMT) and fibrosis, which were mitigated by canagliflozin. High-glucose conditions reduced intracellular GRP78, increased its secretion, and caused EMT-like changes in cultured HK2 cells, which were again inhibited by canagliflozin. Urinary GRP78 increased in STZ mice, and in vitro experiments with recombinant GRP78 suggested that inflammation spread to surrounding tubular cells and that canagliflozin reversed this effect. Under normal glucose culture, canagliflozin maintained sarco/endoplasmic reticulum (ER) Ca2+-ATPase (SERCA) activity, promoted ER robustness, reduced ER stress response impairment, and protected proximal tubular cells. In conclusion, canagliflozin restored subcellular localization of GRP78, SGLT2, and integrin-ß1 and inhibited EMT and fibrosis in DKD. In nondiabetic chronic kidney disease, canagliflozin promoted ER robustness by maintaining SERCA activity and preventing ER stress response failure, and it contributed to tubular protection.

A survey of mental health literacy in parents and guardians of teenagers.

Introduction: Parents and guardians (hereafter caregivers) of teenagers need high levels of mental health literacy (MHL) to manage mental health problems arising in teenagers in their care. Previous studies assessing MHL levels in caregivers of teenagers have reported mixed results, making it difficult to clearly estimate caregiver MHL levels. This study aimed to investigate MHL levels in Japanese caregivers of regular teenagers. Methods: Responses from caregivers (n = 1,397) of students entering junior and senior high schools to a self-administered online questionnaire were analyzed. The questionnaire assessed (a) knowledge about mental health/illnesses and (b) attitudes towards mental health problems in teens in their care (e.g., recognition of depression as a medical illness and intention to engage in helping behaviors). Results: The average proportion of correct answers to the knowledge questions (n = 7) was 55.4%; about one tenth (9.2%) of caregivers correctly answered only one or none of the questions. Few caregivers correctly answered about the life-time prevalence of any mental illnesses (46.1%) and appropriate sleep duration for teenagers' health (16.5%). The proportions of caregivers who had the intention to listen to the teen in their care, consult another person, and seek professional medical help if the teen suffered from depression were 99.5%, 91.5% and 72.7%, respectively. Conclusions: Many teenagers' caregivers appeared to be willing to help the teens in their care if they were suffering from mental health problems. However, there was much room for improvement in knowledge on mental health/illnesses and intention to seek help from medical professionals. Efforts toward better education should be made.

Mechanism of dentin hardness measurements using a dentin hardness measuring device with a light-emitting diode.

Significance: Managing caries is imperative in a rapidly aging society. Current diagnoses use qualitative indices. However, a quantitative evaluation of hardness in a clinical setting may lead to more accurate diagnoses. Previously, hardness meter using indenter with light for tooth monitoring (HAMILTOM) was developed to quantitatively measure tooth hardness. Herein, the physical interpretation of dentin hardness measured using HAMILTOM and the dentin hardness measurement mechanism are discussed. Aim: This study evaluates the mechanism of dentin hardness measurements using HAMILTOM physically and compare the invasiveness to dentin by HAMILTOM with those using a dental probe for palpation. Approach: Eleven bovine dentin samples were used to create caries models. HAMILTOM measured the dark areas, and its indentations were observed using scanning electron microscopy. Also, its invasiveness was evaluated by comparing the results with those from dental probe palpation. Results: The indentation areas were smaller than the dark areas in HAMILTOM, which may be due to exuded water from the dentin sample and the elastic recovery of dentin sample. Additionally, the dental probe indentation was deeper than the HAMILTOM indentations. Conclusions: The results demonstrate that the indentation areas were smaller than the dark areas measured by HAMILTOM, which might contain the influence of exuded water and the deformation of dentin sample. Also, HAMILTOM is less invasive than dental probe palpation. In the future, HAMILTOM may become a standard hardness measuring method to diagnose root caries.

CAD-CAM resin composites: Effective components for further development.

OBJECTIVE: This paper summarizes the effective components of computer-aided design and computer-aided manufacturing (CAD-CAM) resin composites that contribute to achieving greater mechanical properties and further development. METHODS: In silico multi-scale analysis, in silico nonlinear dynamic finite element analysis (FEA), and artificial intelligence (AI) were used to explore the effective components of CAD-CAM resin composites. The effects of the filler diameter and silane coupling ratio on the mechanical properties of CAD-CAM resin composites have been clarified through multi-scale analysis. The effects of the filler contents, and filler and monomer compositions have been investigated by AI algorithms. The fracture behavior of CAD-CAM composite crown was analyzed using in silico non-linear dynamic FEA. The longevity of CAD-CAM composite crown was assessed through step-stress accelerating life testing (SSALT). RESULTS: As the filler diameter decreases, there is an increase in elastic moduli and compressive strengths at the macroscale. At the nanoscale, a decrease in the filler diameter results in a decrease in the maximum value of the maximum principal strain. When the silane coupling ratio decreases, there is a decrease in the elastic modulus and compressive strength. According to the exhaustive search and feature importance analysis based on the AI algorithm, the combination of certain components was narrowed down to achieve a flexural strength of 269.5 MPa. The in silico non-linear FEA successfully detected the sign of the initial crack of the CAD-CAM composite molar crown. The SSALT revealed that CAD-CAM resin composite molar crowns containing nanofillers with a high fraction of resin matrix demonstrated great longevity. SIGNIFICANCE: This paper summarized the effective components of CAD-CAM resin composites for their further development. The integration of in vitro and in silico approaches will expedite the advancement of CAD-CAM resin composites, offering benefits such as time efficiency and reduction of material waste for researchers and manufacturers.

In silico nonlinear dynamic finite-element analysis for biaxial flexural strength testing of CAD/CAM materials.

PURPOSE: The aim of this study was to establish and assess the validity of in silico models of biaxial flexural strength (BFS) tests to reflect in vitro physical properties obtained from two commercially available computer-aided design/computer-aided manufacturing (CAD/CAM) ceramic blocks and one CAD/CAM resin composite block. METHODS: In vitro three-point bending and BFS tests were conducted for three CAD/CAM materials (n = 10): Katana Zirconia ST10 (raw material: super-translucent multilayered zirconia, ST10; Kuraray Noritake Dental, Niigata, Japan), Katana Zirconia HT10 (raw material: highly translucent multilayered zirconia, HT10; Kuraray Noritake Dental), and Katana Avencia N (AN; Kuraray Noritake Dental). Densities, flexural moduli, and fracture strains were obtained from the in vitro three-point bending test and used as an input for an in silico nonlinear finite element analysis. The maximum principal stress (MPS) distribution was obtained from an in silico BFS analysis. RESULTS: The elastic moduli of AN, HT10, and ST10 were 6.513, 40.039, and 32.600 GPa, respectively. The in silico fracture pattern of ST10 observed after the in silico evaluation was similar to the fracture pattern observed after the in vitro testing. The MPS was registered in the center of the tensile surface for all three specimens. The projections of the supporting balls were in the form of a triple asymmetry. CONCLUSIONS: The in silico approach established in this study provided an acceptable reflection of in vitro physical properties, and will be useful to assess biaxial flexural properties of CAD/CAM materials without wastage of materials.

Suicidal Thoughts and Trajectories of Psychopathological and Behavioral Symptoms in Adolescence.

Importance: The suicidal risk of psychopathology in adolescence is suggested to differ based on its longitudinal trajectory, but the comorbidity of these symptom trajectories has not been well examined. This study comprehensively clustered trajectories of multiple psychopathological and behavioral symptoms and examined their associations with suicidal thoughts in adolescence. Objective: To determine which categories and trajectories of psychopathological and behavioral symptoms are associated with suicidal thoughts in adolescence, accounting for comorbid symptoms. Design, Setting, and Participants: This population-based cohort study in Japan used data from the Tokyo Teen Cohort (TTC) study, which was established in 2012 and is currently ongoing. Data from 3 waves of surveys conducted at ages 10, 12, and 16 years from October 2012 to September 2021 were used. Of the adolescents in the cohort, participants with at least 2 evaluations of psychopathological and behavioral symptoms were included. Data were analyzed from December 2022 to March 2023. Exposure: Latent class growth analysis was used to cluster the trajectory of each psychopathological and behavioral symptom. Main Outcomes and Measures: The associations between symptom trajectories and suicidal thoughts at age 16 were examined. Suicidal thoughts were assessed using a self-report questionnaire. Psychopathological and behavioral symptoms were assessed using the 8 subscale scores of the caregiver-report Child Behavior Checklist. Results: This study included 2780 adolescents (1306 female participants [47.0%]). Of the 1920 adolescents with data on suicidal thoughts, 158 (8.2%) had suicidal thoughts. The median (IQR) age was 10.2 (10.0-10.3) years at the first evaluation, 11.9 (11.8-12.1) years at the second evaluation, and 16.3 (16.1-16.5) years at the last evaluation. The clustering pattern of trajectories varied depending on symptom categories. After adjusting for each symptom trajectory and confounders, adolescents with persistent high withdrawn symptoms (odds ratio [OR], 1.88; 95% CI, 1.10-3.21) and those with increasing somatic symptoms (OR, 1.97; 95% CI, 1.16-3.34) had a significantly higher risk of suicidal thoughts than adolescents without these symptoms. There was no interaction between these symptom trajectories and the risk of suicidal thoughts. Conclusions and Relevance: This cohort study found that persistent withdrawn symptoms and increasing somatic symptoms during early to midadolescence were associated with an increased risk of suicidal thoughts in midadolescence, even after accounting for comorbid symptoms and confounders. Attention should be paid to the suicidal risk associated with these symptoms, particularly when they persist or increase in the longitudinal follow-up.

Sex differences in the association between epicardial adipose tissue volume and left atrial volume index.

BACKGROUND: Sex disparities in the association between epicardial adipose tissue volume (EATV) and cardiovascular disease have been reported. The sex-dependent effects of EATV on left atrial (LA) size have not been elucidated. METHODS: Consecutive 247 subjects (median 65 [interquartile range 57, 75] years; 67% of men) who underwent multi-detector computed tomography without significant coronary artery disease or moderate to severe valvular disease were divided into two groups: patients with sinus rhythm (SR) or atrial fibrillation (AF). Sex differences in the association between the EATV index (EATVI) (mL/m2) and LA volume index (LAVI) in 63 SR (28 men and 35 women) and 184 AF (137 men and 47 women) patients were evaluated using univariate and multivariate regression analyses. RESULTS: In overall that includes both men and women, the relationship between EATVI and LAVI was not significantly correlated for patients with SR and AF. The relationship between EATVI and LAVI differed between men and women in both SR and AF groups. In SR patients, there was a positive relationship between EATVI and LAVI in men, but not in women. In contrast, in patients with AF, a negative relationship was found between EATVI and LAVI in women, whereas no association was found in men. CONCLUSIONS: We evaluated sex differences in the association between EATVI and LAVI in patients with either SR or AF, and found a positive relationship in men with SR and a negative relationship in women with AF. This is the first report to evaluate sex differences in the relationship between EATVI and LAVI, suggesting that EAT may play a role, at least in part, in sex differences in the etiology of AF.

Variability in sonographic anterior drawer test measurements of the ankle: Experienced versus beginner examiners.

BACKGROUND: This study aimed to clarify the variability in the measurements of stress sonography of the ankle and determine the effects of examiner experience on the measurements. METHODS: Twenty examiners (10 experienced and 10 beginners) were included in the study. Each examiner performed stress ultrasonography on a patient with a chronic anterior talofibular ligament injury and a patient with an intact ligament using the reverse anterior drawer method. Changes in ligament length before versus after stress were determined. The same 20 examiners performed ultrasonography on two other patients with an injured or intact ATFL using the anterior drawer method. The length change values and variance were compared between the groups using t-tests and F-tests. RESULTS: Using the reverse anterior drawer method, the change in the anterior talofibular ligament length was 3.3 mm (range, 2.2-4.8 mm) in the experienced group and 2.7 mm (0.0-4.1 mm) in the beginner group for the ligament injured patient. The length changes for the patient with intact anterior talofibular ligament were 0.5 mm (0.1-0.9 mm) and 0.4 mm (-0.1-1.5 mm) in the experienced and beginner groups, respectively. There were no significant intergroup differences in measurement amount (P = 0.37) or variance (P = 0.72). Similarly, using the anterior drawer method, no significant differences between the groups were found in measurement amount or variance. CONCLUSION: The quantitative evaluation of stress sonography of the ankle was variable regardless of examiner experience or stress method, particularly in patients with an anterior talofibular ligament injury. The amount of variability appeared to be unacceptably large for clinical application. Our study results highlight the need for technical standardization.

Association between anthropometric indices and 5-year hypertension incidence in the general Japanese population.

No existing reports demonstrate the association between anthropometric indices (body mass index, waist circumference, body roundness index, a body shape index) and hypertension according to sex and age in the general Japanese population. This retrospective analysis involved individuals aged 30-69 years who underwent annual medical checkups at Kagoshima Koseiren Hospital in 2005-2019, and who did not meet hypertension criteria at baseline. The outcome was hypertension incidence after 5 years, and its association with baseline anthropometric indices was evaluated using multivariable logistic regression analysis by sex and age. In 41,902 participants (age 52.3 ± 10.2 years, 47.7% men), 7622 individuals (18.2%) developed hypertension after 5 years. Body mass index, waist circumference, and body roundness index were significantly associated with the development of hypertension in both men and women across all age categories from 30 s to 60 s. In the population with a body mass index <25 kg/m2, waist circumference and body roundness index were significantly associated with hypertension after 5 years. A body shape index was significantly associated with the development of hypertension in men in their 40 s and 50 s but not in women of any age group. The area under the curve values were lower for a body shape index than for body mass index, waist circumference, and body roundness index in both men and women of all age groups. A body shape index was not a stronger indicator for 5-year hypertension incidence than body mass index, waist circumference, or body roundness index in both men and women across age groups from their 30s-60 s. The results of this study will help to more efficiently identify populations at high risk of developing hypertension and provide preventive interventions. A total of 41,902 participants from health checkup programs were stratified by gender and age to investigate the association between baseline anthropometric indices and hypertension incidence over a 5-year period. BMI, WC, and BRI were almost equally effective and showed a better association with risk of developing hypertension in women and young adults compared to men and old adults. Conversely, ABSI showed no greater association than BMI or WC in any age group in both men and women. ABSI, a body shape index; AUC, area under the curve from receiver operating characteristic curve analysis; BMI, body mass index; BRI, body roundness index; WC, waist circumference.

Changes in Urinary Uric Acid Concentration after Dotinurad Administration to Patients with Hyperuricemia: A Post Hoc Analysis of Two Clinical Trials in Japan.

Dotinurad has been approved in Japan as a selective urate reabsorption inhibitor for the treatment of gout and hyperuricemia. The relationship between uric acid crystallization and the use of uricosuric drugs is widely acknowledged; however, the relationship between changes in urinary uric acid concentration and urine pH or volume has not been sufficiently analyzed. Therefore, we investigated the changes in urinary uric acid concentration following dotinurad administration as well as the relationship between urine pH or volume and urinary uric acid concentration. This post hoc analysis used data from 2 clinical trials that included 12 and 26 patients with hyperuricemia who received dotinurad treatment (for 7 days on an inpatient basis and 14 weeks on an outpatient basis, respectively). The urinary uric acid concentration transiently increased in the early stages of dotinurad use and when its dose was increased, but decreased over time. No uric acid concentrations exceeded the soluble limit at any urine pH. An inverse correlation was observed between urine volume and urinary uric acid concentration. This study highlights the significance of adequately managing urinary uric acid concentrations by increasing urine volume and alkalinizing urine to prevent uric acid crystallization during dotinurad administration.

Uncovering associations between gender nonconformity, psychosocial factors, and mental health in adolescents: a birth cohort study.

BACKGROUND: Little information is available on the association between gender nonconformity during adolescence and subsequent mental health. While the distress related to gender nonconformity may be socially produced rather than attributed to individual-level factors, further research is needed to better understand the role of psychosocial factors in this context. METHOD: We analyzed data from the Tokyo Teen Cohort, obtained through random sampling of adolescents born between 2002 and 2004. We used inverse probability weighting to examine the association of gender nonconformity at ages 12 and 14 as a time-varying variable with subsequent mental health at age 16, while accounting for time-fixed and time-varying confounders. Furthermore, we used a weighting approach to investigate the mediating role of modifiable psychosocial factors in this association, addressing exposure-mediator and mediator-mediator interactions. RESULTS: A total of 3171 participants were analyzed. Persistent gender nonconforming behavior at ages 12 and 14 was associated with subsequent depression (ß = 2.02, 95% confidence interval [CI] 0.85 to 3.19) and psychotic experiences (ß = 0.33, 95% CI 0.14 to 0.52) at age 16. The results remained robust in sensitivity analyses. Approximately 30% of the association between gender nonconformity and depression was consistently mediated by a set of psychosocial factors, namely loneliness, bullying victimization, and relationships with mother, father, and friends. CONCLUSIONS: Persistent gender nonconformity during adolescence is associated with subsequent mental health. Psychosocial factors play a vital mediating role in this association, highlighting the essential need for social intervention and change to reduce stigmatization and ameliorate mental health challenges.

Relationship between defecation status and blood pressure level or blood pressure variability.

Blood pressure variability is an independent predictor of cardiovascular disease. Defecation status has also been associated with the risk of developing cardiovascular disease. This study aimed to investigate the association between blood pressure variability and defecation status. A total of 184 participants who could measure their home blood pressure for at least 8 days monthly, both at baseline and 1 year later, were included in this study. All participants had their home blood pressure measured using HEM-9700T (OMRON Healthcare). Day-to-day variability of systolic blood pressure was assessed using the coefficient of variation of home systolic blood pressure during 1 month. Data on defecation status was obtained using a questionnaire survey. Eighty-nine patients had an elevated coefficient of variation at 1 year. The proportion of participants with elevated coefficient of variation at 1 year was significantly higher in the no daily bowel movement group than in the daily bowel movement group (72% vs. 42%, P = 0.001). In multivariable logistic regression analysis with the elevated coefficient of variation at 1 year as the objective variable and age, sex, no daily bowel movement, taking medications, including antihypertensive drugs, laxatives, and intestinal preparations, and coefficient of variation at baseline as independent variables, no daily bowel movement was independently associated with the elevated coefficient of variation at 1 year (odds ratio: 3.81, 95% confidence interval: 1.64-8.87, P = 0.0019). In conclusion, no daily bowel movement was independently associated with elevated day-to-day blood pressure variability at 1 year. Relationship between defecation status and blood pressure level or blood pressure variability.