BACKGROUND: Mitochondria, which harbor their own genome (mtDNA), have attracted attention due to the potential of mtDNA copy number (mtDNA-CN) as an indicator of mitochondrial dysfunction. Although mtDNA-CN has been proposed as a simple and accessible biomarker for metabolic disorders such as metabolic dysfunction-associated steatotic liver disease, the underlying mechanisms and the causal relationship remain insufficiently elucidated. In this investigation, we combined longitudinal epidemiological data, animal studies, and in vitro assays to elucidate the potential causal relationship between reduced mtDNA-CN and the development of steatotic liver disease (SLD). METHODS: We conducted a longitudinal study using data from a health examination cohort initiated in 1981 in Yakumo, Hokkaido, Japan. Data from examinations performed in 2015 and 2022 were analyzed, focusing on 76 subjects without SLD at baseline (2015) to assess the association between baseline mtDNA-CN and subsequent risk of SLD development. In addition, 28-day-old SD rats were fed ad libitum on a 45% high-fat diet and dissected at 2 and 8 weeks of age. Blood and liver mtDNA-CN were measured and compared at each feeding period. Additionally, in vitro experiments were performed using HepG2 cells treated with mitochondrial function inhibitors to induce mtDNA-CN depletion and to examine its impact on intracellular lipid accumulation. RESULTS: Epidemiological analysis showed that the subjects with low mtDNA-CN had a significantly higher odds ratio for developing SLD compared to high (odds ratio [95% confidence interval]: 4.93 [1.08-22.50]). Analysis of the animal model showed that 8 weeks of high-fat diet led to the development of fatty liver and a significant decrease in mtDNA-CN. A further 2 weeks of high-fat diet consumption resulted in a significant decrease in hepatic mtDNA-CN, despite the absence of fatty liver development, and a similar trend was observed for blood. Complementary in vitro experiments revealed that pharmacologically induced mitochondrial dysfunction led to a significant reduction in mtDNA-CN and was associated with increases in intracellular lipid accumulation in HepG2 cells. CONCLUSIONS Our findings suggest that reduced mtDNA-CN may contribute causally to SLD development and could serve as a convenient, noninvasive biomarker for early detection and risk assessment.
Animals ; DNA, Mitochondrial/genetics* ; Humans ; Male ; DNA Copy Number Variations ; Female ; Fatty Liver/blood* ; Rats ; Middle Aged ; Longitudinal Studies ; Rats, Sprague-Dawley ; Adult ; Japan/epidemiology* ; Aged ; Biomarkers/blood* ; Hep G2 Cells ; Diet, High-Fat/adverse effects*

BACKGROUND: This cross-sectional study examined meal patterns based on daily energy intake distribution and their associations with nutrient and food intake, diet quality, and body mass index (BMI). METHODS: Body height, weight, habitual dietary intake and the Healthy Eating Index (HEI)-2020 score by eating occasion were assessed using the validated Meal-based Diet History Questionnaire among employees (465 males and 193 females aged 20-75 years) in the Tokyo Metropolitan Area. Meal patterns were extracted based on % energy intake from breakfast, lunch, dinner, and snacks using K-means clustering by sex. Dietary intake, HEI-2020 score, and BMI were then compared between sex-specific meal patterns. RESULTS: The identified patterns were "large lunch and dinner" (n = 299), "three meals-balanced" (n = 97), and "large dinner" (n = 69) patterns in males and "large dinner" (n = 79); "large afternoon snack" (n = 54) and "large lunch" (n = 60) patterns in females. The HEI-2020 scores were the highest for dinner, followed by breakfast, lunch, and snacks in any meal pattern. Males with the "large dinner" pattern had lower intakes of rice, bread, carbohydrates, dietary fibre, and thiamine; higher intake of alcoholic beverages; and higher HEI-2020 scores than those with other patterns. Females with a "large dinner" pattern had a lower intake of bread, confectionery, total and saturated fats, and carbohydrates; higher intake of fish, meat, and alcoholic beverages; higher HEI-2020 scores; and lower BMI. Thus, a meal pattern with higher energy intake distribution at dinner was associated with higher diet quality among males and females and lower BMI among females in Japanese workers. CONCLUSIONS These findings suggest that improving the quality of the meal with the highest energy contribution could help enhance overall dietary quality and metabolism.
Humans ; Female ; Male ; Middle Aged ; Adult ; Energy Intake ; Body Mass Index ; Cross-Sectional Studies ; Aged ; Meals ; Young Adult ; Tokyo ; Feeding Behavior ; Diet/statistics & numerical data*

The University of Tokyo Disability Services Office and the University of Tokyo Hospital have striven to advance the inclusion of individuals with disabilities and to encourage the co-production of research as well as mental health services with peer support workers. In convergence with these endeavors, the Center for Diversity in Medical Education and Research (CDMER) was founded in 2021. The Center aims to establish an environment and culture that facilitates the participation and success of medical professionals with disabilities. For this purpose, it is essential to integrate the perspective of the social model of disability into medical education and promote co-production in the medical field, which is among the most challenging areas that can realize co-production. The Center is involved in various educational and research activities, including managing educational programs for medical students and supporting student-led research.

Purpose: This study examined the relationship between achievement goals and work values, and the influence of work values on achievement goals.Methods: The subjects were 538 students from four Physical Therapist Vocational Schools. Achievement goals and work values were measured with a questionnaire survey, and Pearson's product-moment correlation coefficient and multiple regression analysis were performed.Results: There was a positive significant correlation between achievement goals and work values. Mastery goals were positively influenced by self-worth and social evaluation, and negatively influenced by the comfortable working environments. Performance approach goals and performance avoidance goals were positively influenced by social evaluation and comfortable working environments, and negatively influenced by self-worth and independence from the organization.Conclusion: Achievement goals and work values were related, and work values were suggested to influence achievement goals.

Purpose: The study aimed to compare the diagnostic performance of washout-parametric imaging (WOPI) with that of conventional contrast-enhanced ultrasound (cCEUS) in differentiating focal liver lesions (FLLs). Methods: A total of 181 FLLs were imaged with contrast-enhanced ultrasound using Sonazoid, and the recordings were captured for 10 minutes in a prospective setting. WOPI was constructed from three images, depicting the arterial phase (peak enhancement), the early portal venous phase (1-minute post-injection), and the vasculo-Kupffer phase (5 or 10 minutes post-injection). The intensity variations in these images were color-coded and superimposed to produce a single image representing the washout timing across the lesions. From the 181 FLLs, 30 hepatocellular carcinomas (HCCs), 30 non-HCC malignancies, and 30 benign lesions were randomly selected for an observer study. Both techniques (cCEUS and WOPI) were evaluated by four off-site readers. They classified each lesion as benign or malignant using a continuous rating scale, with the endpoints representing "definitely benign" and "definitely malignant." The diagnostic performance of cCEUS and WOPI was compared using the area under the receiver operating characteristic curve (AUC) with the DeLong test. Interobserver agreement was assessed using the intraclass correlation coefficient (ICC). Results: The difference in average AUC values between WOPI and cCEUS was 0.0062 (95% confidence interval, -0.0161 to 0.0285), indicating no significant difference between techniques. The interobserver agreement was higher for WOPI (ICC, 0.77) than cCEUS (ICC, 0.67). Conclusion The diagnostic performance of WOPI is comparable to that of cCEUS in differentiating FLLs, with superior interobserver agreement.

Purpose: The study aimed to compare the diagnostic performance of washout-parametric imaging (WOPI) with that of conventional contrast-enhanced ultrasound (cCEUS) in differentiating focal liver lesions (FLLs). Methods: A total of 181 FLLs were imaged with contrast-enhanced ultrasound using Sonazoid, and the recordings were captured for 10 minutes in a prospective setting. WOPI was constructed from three images, depicting the arterial phase (peak enhancement), the early portal venous phase (1-minute post-injection), and the vasculo-Kupffer phase (5 or 10 minutes post-injection). The intensity variations in these images were color-coded and superimposed to produce a single image representing the washout timing across the lesions. From the 181 FLLs, 30 hepatocellular carcinomas (HCCs), 30 non-HCC malignancies, and 30 benign lesions were randomly selected for an observer study. Both techniques (cCEUS and WOPI) were evaluated by four off-site readers. They classified each lesion as benign or malignant using a continuous rating scale, with the endpoints representing "definitely benign" and "definitely malignant." The diagnostic performance of cCEUS and WOPI was compared using the area under the receiver operating characteristic curve (AUC) with the DeLong test. Interobserver agreement was assessed using the intraclass correlation coefficient (ICC). Results: The difference in average AUC values between WOPI and cCEUS was 0.0062 (95% confidence interval, -0.0161 to 0.0285), indicating no significant difference between techniques. The interobserver agreement was higher for WOPI (ICC, 0.77) than cCEUS (ICC, 0.67). Conclusion The diagnostic performance of WOPI is comparable to that of cCEUS in differentiating FLLs, with superior interobserver agreement.