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*

BACKGROUND: The effect of the redox state of human serum albumin (HSA) on the antioxidant properties of the entire body has been a focus of recent research. The usefulness of HSA redox state as a biomarker for reducing oxidative stress has been investigated in clinical settings; however, evidence for its significance as a health index in non-clinical settings is yet to be established. This study aimed to examine the associations between HSA redox state and the atherosclerotic indices of carotid intima-media thickness (IMT) and plaque formation in a rural Japanese population. METHODS: We conducted a cross-sectional study as part of a health check-up program in the rural area of Hokkaido, Japan, at the end of August 2013. A total of 281 residents (124 men and 157 women) were included in the final analysis. Lifestyle-related data were obtained through a self-reported questionnaire, and ultrasound examinations were performed to measure IMT and determine plaque formation. The high-performance liquid chromatography postcolumn bromocresol green method was used to separate HSA into human nonmercaptalbumin and human mercaptalbumin (HMA). RESULTS: We found a significant negative relationship between the fraction of HMA [f(HMA)] and IMT (standardized β = - 0.132, p = 0.03). Moreover, f(HMA) was significantly associated with plaque formation (p < 0.01) with an odds ratio of 0.89 (95% confidence interval, 0.81-0.97) for every 10% increment in f(HMA). CONCLUSIONS We found that the HSA redox state, as determined by f(HMA), was associated with atherosclerotic indices in Japanese subjects. These results suggest that the HSA redox state indicates the risk of developing atherosclerosis.
Adult ; Aged ; Aged, 80 and over ; Atherosclerosis ; epidemiology ; etiology ; Biomarkers ; Carotid Intima-Media Thickness ; statistics & numerical data ; Cross-Sectional Studies ; Female ; Humans ; Japan ; epidemiology ; Male ; Middle Aged ; Oxidation-Reduction ; Risk Factors ; Serum Albumin ; metabolism ; Serum Albumin, Human ; metabolism

Fecal microbiota transplantation (FMT) has been reported as a safe and effective therapy in patients with refractory and recurrent Clostridium difficile infection (CDI). FMT has also been reported as a promising therapy in patients with ulcerative colitis (UC). Both, CDI and UC, are believed to be caused by dysbiosis, such as altered compositions or decreased diversity of the intestinal microbiota. This report describes a patient with UC in remission with a second recurrent episode of CDI, who was treated with FMT. A single FMT performed via colonoscopy completely resolved the patient's diarrhea and eradicated C. difficile bacteriologically without any severe complications. Molecular biological analysis of the patient's fecal microbiota showed that FMT could dramatically change the altered composition of intestinal microbiota and restore its diversity. Despite the restoration of the intestinal microbiota, FMT could not prevent a relapse of UC in this patient. However, it improved the intestinal symptoms of CDI and could prevent further recurrences of CDI.
Clostridium difficile ; Clostridium ; Colitis, Ulcerative ; Colonoscopy ; Diarrhea ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Microbiota ; Recurrence ; Ulcer

BACKGROUND/AIMS: Recent developments in analytical techniques including next-generation sequencing have clarified the correlation between intestinal microbiota and inflammatory bowel disease. Fecal microbiota transplantation (FMT) for patients with ulcerative colitis (UC) is proposed as a potential approach to resolving their dysbiosis; however, its safety and efficacy have not been confirmed. This single-arm, open-label, non-randomized study aimed to evaluate the safety and efficacy of FMT for Japanese patients with UC as the first registered clinical trial in Japan. METHODS: We enrolled 10 patients with active UC despite medical therapy. The donors were the patients' relatives and were carefully screened for infectious diseases. Fecal material was administered via colonoscopy, and the primary endpoint was the presence or absence of serious adverse events related to FMT. The secondary endpoint was a change in partial Mayo score at 12 weeks post-FMT. Scores ≤2 were considered a clinical response. Fecal samples were collected to follow changes in gut microbiota, while extracted complementary DNA were analyzed by a next-generation sequencer. We obtained written informed consent from all patients and donors. This study was approved by our Institutional Review Board and is registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN 000012814). RESULTS: Five patients with moderate disease and five with severe disease were enrolled. No severe adverse effects were observed. One patient achieved clinical response; however, none of the patients' microbiota diversity recovered to the donor levels. CONCLUSIONS: The use of single FMT for UC was safe; however, we failed to show its clinical efficacy and potential to change the intestinal microbiota.
Asian Continental Ancestry Group* ; Colitis, Ulcerative* ; Colonoscopy ; Communicable Diseases ; DNA, Complementary ; Dysbiosis ; Ethics Committees, Research ; Fecal Microbiota Transplantation* ; Gastrointestinal Microbiome* ; Humans ; Inflammatory Bowel Diseases ; Information Services ; Informed Consent ; Japan ; Microbiota ; Tissue Donors ; Treatment Outcome ; Ulcer*

　　In the guidance of technical aspects in the “new nursing staff training guidelines” prepared by the Ministry of Health, Labor and Welfare in December 2009, We were using an e-learning method. We evaluated the achievement of nursing technology item 69 and examined the problems to be solved for the future basic nursing technical guidance. The subjects in the present study were 53 persons who joined the of rookie nursing staff of our hospital in April 2013 (new nurses are all fresh from college). Of the goals indicated in the guidelines, nursing technology item 69 was prepared for the group training course using e-learning. The trainees learned with a focus on simulation. After that each department carried out OJT and evaluation. 　　We aggregated achievement evaluations and carried out questionnaire surveys on the use of e-learning in June, September and March of the following year. We compared and examined the evaluations of achievement in comparison with the previous year evaluations. In March 2014 when the new nursing staff training program ended, it was found that those who attained “a measure of reach 1: can” or “2: as possible under the guidance” accounted for 36.5% of the total number of recruits in 2013, compared to 34.9% in 2012. The ratio of those who highly evaluated “a measure of reach 4: have knowledge” remarkably increased from4.5% to23.4%, and that of inexperienced persons or people who did not evaluate decreased from 29.2% to 4.2%. This showed that the self-learning and utilizing e-learning at their own pace proactively helped them to acquire basic nursing skills. However, a problem remained that too much time was required for evaluation, because it has been actually evaluated over 100 fields due to detailed e-learning items, the limited number of desk-top computers.

We performed combination therapy with modified oxaliplatin/l-LV/5-FU (mFOLFOX) in a patient with recurrent colorectal cancer who had peritonitis carcinomatosis. In this patient, mFOLFOX therapy resulted in disappearance of ascites and a decrease in carbohydrate antigen 19-9 (CA19-9), and improved quality of life (QOL) of the patient. This 62-year-old man was diagnosed with ascending colon cancer and metastatic cancer of the liver. Right hemicolectomy and right hepatic lobectomy were performed. We had started to treat with TS-1 in ambulatory care, however, he had peritonitis carcinomatosis with massive ascite reservoir on CT and peritoneal dissemination after a half year postoperatively. Furthermore, his ECOG Performance Status (PS) was rated as level 3. Therefore, we performed puncture of ascites and palliative mFOLFOX6 therapy. After ten courses, ascites and abdominal induration had disappeared and PS recovered to level 1. At present, CPT-11/l-LV/5-FU (FOLFIRI) are being administered for peripheral neuropathy and metastatic tumor associated with mFOLFOX6. The patient is spending his daily life satisfactory after FOLFIRI without abdominal swelling or ascites, and thus mFOLFOX6 may be an option for palliative therapy against massive ascites in patients with advanced colorectal cancer. The usefulness of palliative mFOLFOX6 therapy for patients with massive ascites should be evaluated in a well-designed clinical trial.Palliat Care Res 2008; 3(2): 316-320