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*

Objectives: We compared cancer patients who were discharged home from inpatients hospices (Home), and who died at hospices (PCU) as a comparison group regarding patients’ quality of life, to clarify the patients’ experience after discharge home. Methods: We send self-reported questionnaires to bereaved families of cancer patients who were discharged home from 12 Japanese nation-wide hospices and died without readmission to the hospicies during Janually 2010 and August 2014. We used bereaved families’ data of patients who died at the same hospices during the same period of J-HOPE3 study. Results: We sent 495 questionnaires (returned 47.3%) and analyzed data of 188 as Home. The data of 759 bereaved families of J-HOPE3 study were also analyzed as PCU. In Good Death Inventory, Home was associated with higher score on some items (staying at favorite place, having pleasure, staying with families and friends, being valued as a person), and PCU was associated with higher score on being free from pain or other physical distress. Conclusions: Patients who were discharged home from inpatient hospices had good environmental QOL, but hospices may be better in palliation of symptoms.

Objective: This study aimed to determine if the discrepancy between depression severity rated by clinicians and that reported by patients depends on key behavioral/psychological features in patients with mood disorders. Methods: Participants included 100 patients with mood disorders. First, we examined correlations and regressions between scores on the Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI). Second, we divided the participants into those who provided 1) greater ratings for the BDI compared with the HAMD (BDI relative-overrating, BO) group, 2) comparable ratings for the BDI and HAMD (BDI relatively concordant, BC) group, or 3) less ratings for the BDI (BDI relative-underrating, BU) group. Adverse childhood experiences, autistic-like traits, and coping styles were evaluated with a six-item short version of the Childhood Trauma Questionnaire (CTQ-6), the Social Responsiveness Scale for Adults (SRS-A), and the Ways of Coping Checklist (WCCL), respectively. Results: A significant correlation was found between HAMD and BDI scores. Total and emotional abuse subscale scores from the CTQ-6, and the self-blame subscale scores from the WCCL were significantly higher for the BO group compared with the BU group. The BO group also elicited significantly higher SRS-A total scores than did the other groups. Conclusion These findings suggest that patients with adverse emotional experiences, autistic-like traits, and self-blame coping styles perceive greater distress than that evaluated objectively by clinicians. The results indicate the need for inclusion of subjective assessments to effectively evaluate depressive symptoms in patients deemed to have these psycho-behavioral concerns.

Methods: We investigated 154 foramina at L5–S1 in 77 patients. All the patients had degenerative lumbar disorders and had undergone both conventional MRI and 3D-MRI during the same visit. Differences between the FSRs calculated from conventional and 3D-MRI reconstructions and any correlations with the plain radiography findings were assessed. Results: In foramina that had a FSR of <50% on conventional MRI, the difference between the FSR obtained using conventional MRI and 3D-MRI was 5.1%, with a correlation coefficient of 0.777. For foramina with a FSR ≥50% on conventional MRI, the difference was 20.2%, with a correlation coefficient of 0.54. FSR obtained using 3D-MRI was significantly greater in patients who required surgery than in those who were successfully treated with conservative methods (88% and 42%, respectively). Segments with spondylolisthesis or lateral wedging showed higher FSRs than those without these conditions on both types of MRI. Conclusions FSRs <50% obtained using conventional MRI were sufficiently reliable; however, the results were inaccurate for FSRs ≥50%. Patients with high FSRs on 3D-MRI were more likely to require surgical treatment. Therefore, 3D-MRI is recommended in patients with suspected stenosis detected using conventional MRI or plain radiographs.

Methods: We investigated 154 foramina at L5–S1 in 77 patients. All the patients had degenerative lumbar disorders and had undergone both conventional MRI and 3D-MRI during the same visit. Differences between the FSRs calculated from conventional and 3D-MRI reconstructions and any correlations with the plain radiography findings were assessed. Results: In foramina that had a FSR of <50% on conventional MRI, the difference between the FSR obtained using conventional MRI and 3D-MRI was 5.1%, with a correlation coefficient of 0.777. For foramina with a FSR ≥50% on conventional MRI, the difference was 20.2%, with a correlation coefficient of 0.54. FSR obtained using 3D-MRI was significantly greater in patients who required surgery than in those who were successfully treated with conservative methods (88% and 42%, respectively). Segments with spondylolisthesis or lateral wedging showed higher FSRs than those without these conditions on both types of MRI. Conclusions FSRs <50% obtained using conventional MRI were sufficiently reliable; however, the results were inaccurate for FSRs ≥50%. Patients with high FSRs on 3D-MRI were more likely to require surgical treatment. Therefore, 3D-MRI is recommended in patients with suspected stenosis detected using conventional MRI or plain radiographs.

This study aimed to examine characteristics of physical functions, physical activity, and cognitive functions among community-dwelling older people who stopped driving automobiles. Participants were 589 community-dwelling older people (age: 65–89, 71.4 ± 5.1 years; 403 men, 186 women). The participants underwent nine physical assessments—hand grip strength, knee extension strength, timed up-and-go test, chair stand, one leg standing with open eyes, functional reach, vertical jump, preferred gait speed, maximal gait speed—and were evaluated for physical activity; and five cognitive assessments—the Mini-Mental State Examination (MMSE), Logical Memory I and II (WMS-R LM-I, LM-II) subtests of the Wechsler Memory Scale-Revised; and Trail Making Test A and B (TMT-A, TMT-B). They were divided into current driver (379 men, 169 women) and driving cessation (24 men, 17 women) groups. Among men, the driving cessation group had poorer vertical jump, TMT-A, and TMT-B results, while women had poorer hand grip strength, one leg standing with open eyes, WMS-R LM-II, and LM-II results, and longer inactivity time, compared with the current driver group and adjusted for covariates (P < 0.05 for all). The findings suggest driving cessation among community-dwelling older people is significantly associated with poorer physical functions, physical activity, and cognitive functions compared with those in current drivers.

Carcinosarcoma ; Choriocarcinoma ; Conflict of Interest ; Endometrial Neoplasms ; Female ; Gestational Trophoblastic Disease ; Humans ; Japan ; Pharmacists ; Pregnancy ; Sarcoma ; Trophoblasts

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT).METHODS: The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes.RESULTS: The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS.CONCLUSION: CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.
Antigens, CD274 ; Biopsy ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Flow Cytometry ; Heavy Ion Radiotherapy ; Humans ; Radiotherapy ; Treatment Outcome ; Uterine Cervical Neoplasms

We report a 48-year-old man who underwent hybrid aortic repair for visceral aortic patch (VAP) aneurysm. He had undergone descending thoracic aortic repair for post-dissection aneurysm at the age of 25, ascending aorta and proximal aortic arch aneurysm repair at the age of 27, and residual thoracoabdominal dissecting aortic aneurysm repair with VAP reconstruction at the age of 28. During 20 years of follow-up, the VAP gradually enlarged and eventually reached 70×61 mm in diameter. Considering a possible severe adhesion after 2 previous left thoracotomies, we planned a 2-staged hybrid aortic repair. First, we performed reno-visceral debranching and as a second stage operation, endovascular aortic repair was performed successfully 39 days after the first-stage operation.