INTRODUCTION: No reports on both blood and fecal bile acids (BAs) in patients with nonalcoholic fatty liver disease (NAFLD) exist. We simultaneously assessed the serum and fecal BA patterns in healthy participants and those with NAFLD. METHODS: We collected stool samples from 287 participants from 5 hospitals in Japan (healthy control [HC]: n = 88; mild fibrosis: n = 104; and advanced fibrosis group: n = 95). Blood samples were collected and analyzed for serum BAs and 7α-hydroxy-4-cholesten-3-one (C4)—a surrogate marker for BA synthesis ability—from 141 patients. Concentrations of BAs, including cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid, ursodeoxycholic acid, and lithocholic acid (LCA), were measured using liquid chromatography-mass spectrometry. RESULTS: The total fecal BA concentration was significantly higher in the NAFLD group with worsening of fibrosis than in the HC group. Most of the fecal BAs were secondary and unconjugated. In the fecal BA fraction, CA, DCA, chenodeoxycholic acid, ursodeoxycholic acid, and LCA were significantly higher in the NAFLD than in the HC group. The total serum BA concentration was higher in the NAFLD group with worsening of fibrosis than in the HC group. In the serum BA fraction, CA, LCA, and C4 concentrations were significantly higher in the NAFLD than in the HC group. DISCUSSION: Fecal and serum BA and C4 concentrations were high in patients with NAFLD with worsening of fibrosis, suggesting involvement of abnormal BA metabolism in NAFLD with fibrosis progression. Abnormalities in BA metabolism may be a therapeutic target in NAFLD with fibrosis.

BACKGROUND: Renin suppression in primary aldosteronism indicates mineralocorticoid receptor activation via excessive aldosterone secretion, inducing renal damage. We investigated whether the reversal of renin suppression after the initiation of mineralocorticoid receptor antagonist therapy was associated with long-term renal outcomes in medically treated patients with primary aldosteronism. METHODS: This retrospective cohort study included 318 patients with primary aldosteronism treated with mineralocorticoid receptor antagonist between 2008 and 2020 at the Yokohama Rosai Hospital in Japan. The posttreatment renin status was defined as unsuppressed (ie, reversal of renin suppression) when individual plasma renin activity after the initiation of mineralocorticoid receptor antagonist (post-plasma renin activity) was ≥1.0 ng/mL per hour; otherwise, it was defined as suppressed. We analyzed the association of posttreatment renin status with subsequent longitudinal estimated glomerular filtration rate changes using linear mixed-effects models for repeated measurements, adjusting for potential confounders. RESULTS: The posttreatment renin status of 119 patients was unsuppressed (median post-plasma renin activity, 1.7 ng/mL per hour) and that of 199 patients was suppressed (median post-PRA, 0.5 ng/mL per hour). Through the median follow-up period of 3.1 years, the decline in estimated glomerular filtration rate was milder among patients with the unsuppressed posttreatment renin (−0.46 [95% CI, −0.63 to −0.28] mL/min per 1.73 m ² per year) than those with suppressed posttreatment renin (−1.41 [95% CI, −1.56 to −1.27] mL/min per 1.73 m ² per year; difference, 0.96 [95% CI, 0.72–1.20] mL/min per 1.73 m ² per year). CONCLUSIONS: Our findings may highlight the importance of reversing renin suppression with optimal mineralocorticoid receptor antagonist titration in medically treated primary aldosteronism, which could mitigate adverse renal outcomes.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: The mental health of children and adolescents is a growing public health concern, with increasing rates of depression and anxiety impacting their emotional, social, and academic well-being. In Japan, access to timely psychiatric care is limited, leading to extended waiting periods that can range from three months to a year. AI-driven chatbots, such as emol, which integrate Acceptance and Commitment Therapy (ACT), show potential as digital solutions to support young patients during these waiting times. The AI chatbot emol was selected based on a comprehensive review of Japanese mental health technology applications, including in-person evaluations with company representatives. Objective: This exploratory, parallel-group randomized controlled trial examined the feasibility of using AI chatbot emol with pediatric and adolescent individuals on psychiatric waiting lists. Methods: Participants aged 12-18 years were recruited from four hospitals in Kanagawa Prefecture and randomly assigned to either an intervention group, receiving eight weekly chatbot sessions, or a control group, receiving standard mental health information. The primary outcome was change in Patient Health Questionnaire-9 (PHQ-9) scores from pre- to post-intervention. Secondary assessments, such as voice and writing pressure analysis, provided additional engagement metrics, with data collected at baseline, during the intervention, and at week 9. Results: Of the 96 eligible individuals on psychiatric waiting lists, eight expressed interest, and three provided initial consent. However, all participants subsequently withdrew or were excluded, resulting in no evaluable data for analysis. Low engagement may have been influenced by the perceived irrelevance of digital tools, complex protocols, and privacy concerns． Conclusions: Significant barriers to engagement suggest that digital interventions may need simpler protocols and trusted environments to improve feasibility. Future studies could test these interventions in supportive settings, like schools or community centers, to enhance accessibility and participation among youth. Clinical Trial: Trial Registration: Japan Registry of Clinical Trials (jRCT) jRCT1032230427; https://jrct.niph.go.jp

For square contingency tables with ordered categories, the marginal homogeneity model is represented by various expressions, and some extensions of the marginal homogeneity model were proposed. Herein we consider the marginal continuation-ratio to examine a new expression of the marginal homogeneity model. We also propose an extension of the marginal homogeneity model using the ratio of marginal continuation-ratios; namely, the marginal continuation odds ratio. The proposed model can be interpreted in various ways. Additionally, we propose a generalization of it, and decompose the marginal homogeneity model using the generalized model. Furthermore, we extend the models and decompositions into multi-way contingency tables.

Background: Loneliness is a global issue, and primary care physicians play an important role in assessing and intervening with loneliness. This study aimed to examine the association between having a usual source of care (USC) or a good quality of primary care, and loneliness. Methods: This cross-sectional study was conducted in Japan in 2022. A total of 6,000 residents were randomly sampled from the general population, aged 20–74 years. The outcome was the total score of the University of California, Los Angeles (UCLA) 3-item loneliness scale. The exposure included USC and the Person-Centered Primary Care Measure (PCPCM), which assesses the quality of primary care. We conducted a linear regression analysis to adjust for age, sex, educational status, annual household income, self-rated health, living status (whether alone or not), and the existence of physical health problems. Results: Of the 6,000 residents, 1,277 responded to the survey. The median score of the UCLA 3-item loneliness scale was 6.0 and the mean total score of the PCPCM was 2.62. Of the 1,277 individuals, 713 (55.8%) had USC. Having USC was significantly associated with lower scores on the UCLA 3-item loneliness scale; the coefficient was −0.34 (95% confidence interval (CI): −0.57 to −0.12). Also, the total PCPCM score was significantly associated with lower loneliness scores; the coefficient was −0.56 (P < 0.001, 95% CI: −0.78 to −0.35). Conclusions: Having USC and a better quality primary care were associated with a lower loneliness score. The quality of primary care could be a factor to mitigate patient loneliness.