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Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic disease for which no effective treatment is available. Transforming growth factor-β (TGF-β) is thought to be involved in the pathogenesis of IC/PBS, and previous studies have suggested that administrations of a TGF-β inhibitor significantly ameliorated IC/PBS in a mouse model. However, the molecular mechanisms underlying the therapeutic effect of a TGF-b inhibitor on IC/PBS has not been comprehensively analyzed. TGF-β has a variety of actions, such as regulation of immune cells and fibrosis. In our study, we induced IC/PBS-like disease in mice by an intravesical administration of hydrogen peroxide (H₂O₂) and examined the effects of three TGF-β inhibitors, Repsox, SB431542, and SB505124, on the urinary functions as well as histological and gene expression profiles in the bladder. TGF-β inhibitor treatment improved urinary function and histological changes in the IC/PBS mouse model, and SB431542 was most effective among the TGF-β inhibitors. In our present study, TGF-β inhibitor treatment improved abnormal enhancement of nociceptive mechanisms, immunity and inflammation, fibrosis, and dysfunction of bladder urothelium. These results show that multiple mechanisms are involved in the improvement of urinary function by TGF-β inhibitor.

The intellectual foundation of early modern Japan was provided by Confucianism--a system of knowledge set forth in Chinese classical writings. In order to gain access to this knowledge, the Japanese applied reading markers to modify the original Chinese to fit the peculiarities of Japanese grammar and pronunciation. Confucian education started by having the children memorize these Japanese readings ("kundoku") of the Chinese classics by endless recitation ("sodoku"). This article will examine the significance of this study method in order to demonstrate the following: 1. The recitation of the Chinese classics led to these texts being "incorporated" into the body, where they become the "intellectual language" of thought and speech. 2. This quality of "incorporation" was appreciated because it fostered the unity of thought and behavior, leading to the formation of a strong-willed subject. 3. This idea of "incorporation" stands in stark contrast to the modern conception of knowledge that stresses objectivity and transparency, and ignores the pedagogical significance of the body.

Background: With increasingly aging societies, a comprehensive strategy for dementia research is important. The Organized Registration for the Assessment of dementia by the Nationwide General consortium toward Effective treatment (ORANGE) Registry is the first longitudinal multicenter prospective trial-ready cohort in Japan.Objective: To establish a large cohort for use in clinical trials and research in Japan.Methods: This registry, based on communities, hospitals, and nursing homes, covers three dementia stages (preclinical, mild cognitive impairment [MCI], and advanced dementia), and includes more than 30 hospitals. We analyzed enrollment and 1-year follow-up data for disease progression.Results: There were 1450 registered patients (649 men, 801 women; mean age, 77.92±6.70 years; mean Mini-Mental State Examination [MMSE] score, 25.19±2.76). The conversion rates from MCI to dementia and MCI to normal were 14.3% and 1.1%, respectively. High Clinical Dementia Rating score (odds ratio [OR] = 11.085, 95% confidence interval [CI]:1.619-75.913, p = 0.014), low MMSE score (OR = 0.835, 95% CI: 0.761-0.917, p < 0.001), high Geriatric Depression Scale score (OR = 1.093, 95% CI: 1.005-1.189, p = 0.038), and low body mass index (OR = 0.895, 95% CI: 0.829-0.967, p = 0.005) at enrollment were significant factors for conversion.Conclusion: The ORANGE MCI Registry is an established registry that facilitates creation of trial-ready cohorts to accelerate promotion of clinical trials with low reversion rates as it originates from a hospital. One-year follow-up analysis suggested assessing various factors for conversion risk. Further analyses will be possible in future with registry expansion. We will continue to refine this registry, including how it can be used more efficiently. [ABSTRACT FROM AUTHOR]

Objective: To develop a combined index using cognitive function and instrumental activities of daily living (IADL) to discriminate between Clinical Dementia Rating (CDR) scores of 0.5 and 1 in the clinical setting, and to investigate its optimal cutoff values and internal and external validities., Methods: We included outpatients aged 65-89 years with CDR scores of 0.5 or 1. The optimal cutoff values and internal validity were verified using Japanese memory clinic-based datasets between September 2010 and October 2021 [National Center for Geriatrics and Gerontology (NCGG) datasets]. Cognitive function and IADL were assessed using the Mini-Mental State Examination (MMSE) and Lawton Index (LI), respectively. The optimal cutoff values were defined using the Youden Index. To verify internal validity, sensitivity and specificity were calculated using stratified 5-fold cross-validation. To verify external validity, sensitivity and specificity of the optimal cutoff values were assessed in the Organized Registration for the Assessment of dementia on Nationwide General consortium toward Effective treatment (ORANGE) Registry dataset between July 2015 and March 2022, which has multicenter clinical data., Results: A total of 800 (mean age, 77.53 years; men, 50.1%) and 1494 (mean age, 77.97 years; men, 43.3%) participants comprised the NCGG and ORANGE Registry datasets, respectively. The optimum cutoff values for men and women were determined as MMSE < 25 and LI < 5 and MMSE < 25 and LI < 8, respectively; such a combined index showed good discriminative performance in internal (sensitivity/specificity: men, 92.50/73.52; women, 88.57/65.65) and external validities (men, 81.43/77.62; women, 77.64/74.67)., Conclusion: The index developed is useful in discriminating between CDR scores of 0.5 and 1 and should be applicable to various settings, such as memory clinics and clinical research., (© Copyright 2024 Physicians Postgraduate Press, Inc.)