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*

Objective: The addition of maintenance olaparib to bevacizumab demonstrated a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the PAOLA-1/ENGOT-ov25 trial (NCT02477644). We evaluated maintenance olaparib plus bevacizumab in the Japan subset of PAOLA-1. Methods: PAOLA-1 was a randomized, double-blind, phase III trial. Patients received maintenance olaparib tablets 300 mg twice daily or placebo twice daily for up to 24 months, plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total. This prespecified subgroup analysis evaluated investigator-assessed PFS (primary endpoint). Results: Of 24 randomized Japanese patients, 15 were assigned to olaparib and 9 to placebo. After a median follow-up for PFS of 27.7 months for olaparib plus bevacizumab and 24.0 months for placebo plus bevacizumab, median PFS was 27.4 versus 19.4 months, respectively (hazard ratio [HR]=0.34; 95% confidence interval [CI]=0.11–1.00). In patients with tumors positive for homologous recombination deficiency, the HR for PFS was 0.57 (95% CI=0.16–2.09). Adverse events in the Japan subset were generally consistent with those of the PAOLA-1 overall population and with the established safety and tolerability profiles of olaparib and bevacizumab. Conclusion: Results in the Japan subset of PAOLA-1 support the overall conclusion of the PAOLA-1 trial demonstrating that the addition of maintenance olaparib to bevacizumab provides a PFS benefit in patients with newly diagnosed, advanced ovarian cancer.

We encountered a case where opioids were effective for excessive sweating caused by secondary generalized hyperhidrosis associated with cancer. ​​A 64-year-old woman diagnosed with metastatic renal cell carcinoma was admitted to the palliative care unit with right hip pain caused by bone metastasis and sudden excessive sweating. An increased dose of fentanyl transdermal patch provided pain relief. Excessive sweating seemed to have occurred due to neoplastic fever initially, but antipyretic analgesics and steroids were ineffective. Prophylactic use of immediate-release oxycodone provided excessive sweating relief. Finally, we consider that hypothalamus and fentanyl transdermal patch were involved in excessive sweating. Opioids may suppress sweating by acting on the hypothalamus.

  In 2013, the Government of Japan issued “Japan Revitalization Strategy”, in which facilitation of overseas expansion of Japanese drugs, medical equipment, health services, and health system through Public Private Partnership (PPP) is included. In alignment with this strategy, ministries and agencies have initiated on various health project, one of which is “Project for global growth of medical technologies, systems and services through human resource development”funded by the Japan Ministry of Health, Labour, and Welfare from 2015. As an administrative organization of this project, National Center for Global Health and Medicine (NCGM) has organized 119 project for 4 years from 2015 to 2018. This report summarizes the experiences and the results of evaluation in terms of program management, expansion of introduced health technologies and the health impact. As the results, the overall project management was satisfactory from the viewpoints of varieties of project, the execution rates. Then, health technologies were adopted in the national guidelines or policies and 17 introduced medical products were purchased by local governments. When it comes to health impacts, 19646 health staffs were trained through this program for 4 years and 912334 persons were estimated as beneficiaries by 29 project in 2017. Based on data shown as above, the overall achievement of this program should be considered satisfactory. Since this program is unique among other PPP program in Japan as well as other countries as the program scheme to promote expansion of medical products through human resource development, the experiences should provide some insights about the ways to facilitate PPP in health sector. In order to extract the Tips of good practices for future activities, further analysis on each project is necessary.

OBJECTIVES: To clarify the prevalence and characteristics of pain associated with sarcopenia and to verify the usefulness of evaluation of pain for sarcopenia. METHODS: In total, 759 community-dwelling people (aged 65–79 years) with or without sarcopenia and lower limb pain were classified into 4 groups (NSp, nonsarcopenia; NSpP, nonsarcopenia with pain; Sp, sarcopenia; and SpP, sarcopenia with pain). Body composition, motor function, history of fractures since age 50 years, and number of falls in the past 1 year were compared between the groups. RESULTS: Participant proportions by group were: NSp, 53.9%; NSpP, 42.8%; Sp, 1.3%; and SpP, 2.0%. Participants with lower limb pain showed low single leg standing, walking speed, and 2-step value scores and high 25-question Geriatric Locomotive Functional Scale (GLFS-25) score after adjusting for age, sex, body mass index, and presence of sarcopenia. The SpP group showed lower functional reach test and higher GLFS-25 scores than the Sp group. Regarding the history of fractures since 50 years of age and falls in past 1 year, a high retention rate of fracture was noted in the NSpP group. They also experienced significantly more falls in the past 1 year than those in the NSp group. The SpP group noted more falls and fractures although it was insignificant. CONCLUSIONS: The results indicate that participants with lower limb pain showed declining motor function and a high risk for falls and fractures. Sarcopenia could escalate this risk. Therefore, evaluating patients for both pain and sarcopenia may be useful for risk assessment and treatment.
Accidental Falls ; Aged ; Body Composition ; Body Mass Index ; Humans ; Leg ; Lower Extremity ; Prevalence ; Risk Assessment ; Sarcopenia ; Walking

A community-based medicine program in the postgraduate clinical training system has been offered as a mandatory program since 2004. Training sites range from clinical attachments in rural/remote areas to public health centers in the city. The role of the program director is important for enhancing the community-based medical program and raising resident doctors. Unique training programs have been carried out, such as medical training in the afflicted area of the earthquake/Tsunami disaster area as well as an exchange program between Hokkaido and Kagoshima residents. The Japanese healthcare system is drawing global attention and local demand. Enrichment of the community-based medicine program is vital for the human resource development that makes the Japanese healthcare system innovative and sustainable.

"Quality of education" has various definitions, and the definitions are classified mainly into five categories. Introducing the definition categories of "quality of education" , we analyze what aspects of the postgraduate clinical training system for physicians as an educational program have been reconsidered and redesigned. According to the analysis, we propose to introduce a programmatic assessment, which compose of several assessment methods, for evaluation at each stage of medical education from undergraduate to continuous professional development. Realizing such evaluation, we also propose to introduce a student/trainee assessment from a patient's perspective.

"The Ordinance of Ministry of Health, Labor and Welfare on Japanese Postgraduate Medical Training System" from 2020 was announced to each prefectural governor on July 3rd, 2018. This Medical Training system has been reviewed once every five years, and has been strongly aware of the consistency between the model core curriculum of the undergraduate medical education and the continuing professional development of Japan Medical Association. In this journal, Postgraduate Education Committee in Japan Society for Medical Education has published six installments of a series entitled "Japanese Medical Training System and Medical Education" . We reviewed the series and discussed medical education trends surrounding the postgraduate medical training system and issues in the committee. We will be reporting the information as part of the seventh installment of the series.

Medical education towards a specialty is a core stage of training for medical doctors. The specialty training system in Japan was initially organized by various academic societies and was recently integrated under Japan Medical Specialty Board, which was established in 2014. From April 2018, a revised specialty training system will begin and be based on new program guidelines. Its main concepts are professional autonomy, quality assurance of the medical specialty board and trustworthy medical consultation. As with undergraduate education, global standards are recently required in postgraduate education. Consistent outcome policy throughout undergraduate and postgraduate education and workplace-based assessment can hopefully be established.

Under the current postgraduate clinical training system for physicians, three principles have been emphasized in its basic tenets; cultivation of character appropriate for physicians, generation of awareness to the societal role of medical science and healthcare, and mastery of basic clinical skills needed to respond appropriately to injuries and illnesses frequently encountered in general practice. In accordance with its quinquennial review rule, the Clinical Training Committee under the Medical Caucus of the Healthcare Professions Council released draft revisions of a notification published by the Director general of the Health Policy Bureau of the Ministry of Health, Labor and Welfare in March, 2018. The document is entitled "On the operation of the ordinance concerning the postgraduate clinical training prescribed in the paragraph (1) of Article 16-2, Medical Practitioners Act" .　A Key distinction of the revised draft is new learning outcomes featuring core values shared by physicians: commitment to physicians' societal mission of public health, altruistic behavior, respect for humanity, and maintaining one's own integrity. Another key distinction is securement of longitudinal consistency in the set of required faculties, from medical school curriculum to continuing professional development programs. Further improvements in systems and environments to enhance devotion to life-long learning are needed.