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*

Methods: Among 399 patients who underwent ASD surgery, 62 (≥5 levels fused, >2-year follow-up) underwent fusion from T9–10 to L5 (group L, n=21) or to S2–alar–iliac (group S, n=41). Spinal alignments, Scoliosis Research Society (SRS)-22 scores, performance of activities (clipping toenail, wiping buttock, and wearing socks), proximal and distal junctional failure (PJF+DJF), rod fractures (RFs), and overall revision rates (RRs) were compared between the groups. Results: Group L included younger patients and had longer follow-ups when compared with group S. Although the preoperative pelvic incidence and SRS sagittal modifiers were better in group L, postoperative spinal restorations were nonpathological in both groups. Both groups showed similar deformity progression at the 2-year follow-up; however, group L had lower SRS-22 pain scores. Although “wiping buttocks” did not differ between the groups, the performance of “clipping toenails” and “wearing socks” was poorer in group S at 2 years (possible, group S; 40% vs. group L; 85%–90%). The RRs did not differ between the groups; however, the PJF+DJF rate was higher in group L. DJF was not observed in group S, but occurrence of RFs was noted. Conclusions Although poorer SRS-22 pain scores might be related to lumbosacral mobility, sufficient restoration, equivalent deformity progression, and similar RRs with better activity imply that lumbosacral preservation should be considered in younger patients with moderate deformities.

Introduction : The appropriate size of the regional coverage area for primary care in Japan has been unclear. The aim of this study was to determine the geographical distribution of primary care clinics for elderly ambulatory diabetic patients.
Methods : Using an insurance claims database, we extracted data of patients aged 75 years and older requiring ambulatory diabetic care in May 2010 in Ibaraki prefecture. The geographical distance from each municipal office to the clinics was analyzed.
Results : A total of 17,717 data points were extracted from the database. Data points that could not be mapped due to coding errors were eliminated, resulting in 17,144 (96.8%) data points that were ultimately analyzed. The median [25th-75th percentile] geographical distance was 5.5 [2.3-9.9] km. The distance was not related to municipal population, aging rate, or area size.
Conclusion : The coverage area for diabetic care in this primary care setting was estimated. For most elderly ambulatory diabetic patients, clinics are distributed within a 10-km radius area. Further investigation is needed to clarify primary care coverage areas that result in the most efficient use of medical resources.

PURPOSE: To examine the effects of conservative and surgical treatments for nocturnal leg cramps in patients with lumbar spinal stenosis (LSS). Nocturnal leg cramps is frequently observed in patients with peripheral neuropathy. However, there have been few reports on the relationship between nocturnal leg cramps and LSS, and it remains unknown whether conservative or surgical intervention has an impact on leg cramps in patients with LSS. MATERIALS AND METHODS: The subjects were 130 LSS patients with low back and leg pain. Conservative treatment such as exercise, medication, and epidural block was used in 66 patients and surgical treatment such as decompression or decompression and fusion was performed in 64 patients. Pain scores and frequency of nocturnal leg cramps were evaluated based on self-reported questionnaires completed before and 3 months after treatment. RESULTS: The severity of low back and leg pain was higher and the incidence of nocturnal leg cramps was significantly higher before treatment in the surgically treated group compared with the conservatively treated group. Pain scores improved in both groups after the intervention. The incidence of nocturnal leg cramps was significantly improved by surgical treatment (p=0.027), but not by conservative treatment (p=0.122). CONCLUSION: The findings of this prospective study indicate that the prevalence of nocturnal leg cramps is associated with LSS and severity of symptoms. Pain symptoms were improved by conservative or surgical treatment, but only surgery improved nocturnal leg cramps in patients with LSS. Thus, these results indicate that the prevalence of nocturnal leg cramps is associated with spinal nerve compression by LSS.
Adult ; Aged ; Aged, 80 and over ; Decompression, Surgical ; Female ; Humans ; Leg/*pathology ; Low Back Pain/epidemiology/etiology ; Male ; Middle Aged ; Pain/*epidemiology/*etiology ; Prospective Studies ; Questionnaires ; Spinal Stenosis/*complications/*physiopathology/surgery

PURPOSE: The pathological mechanism of lumbar spinal stenosis is reduced blood flow in nerve roots and degeneration of nerve roots. Exercise and prostaglandin E1 is used for patients with peripheral arterial disease to increase capillary flow around the main artery and improve symptoms; however, the ankle-brachial index (ABI), an estimation of blood flow in the main artery in the leg, does not change after treatment. Lumbar spinal nerve roots contain somatosensory, somatomotor, and unmyelinated autonomic nerves. Improved blood flow by medication with prostaglandin E1 and decompression surgery in these spinal nerve roots may improve the function of nerve fibers innervating muscle, capillary, and main vessels in the lower leg, resulting in an increased ABI. The purpose of the study was to examine whether these treatments can improve ABI. MATERIALS AND METHODS: One hundred and seven patients who received conservative treatment such as exercise and medication (n=56) or surgical treatment (n=51) were included. Low back pain and leg pain scores, walking distance, and ABI were measured before treatment and after 3 months of conservative treatment alone or surgical treatment followed by conservative treatment. RESULTS: Low back pain, leg pain, and walking distance significantly improved after both treatments (p<0.05). ABI significantly increased in each group (p<0.05). CONCLUSION: This is the first investigation of changes in ABI after treatment in patients with lumbar spinal stenosis. Improvement of the spinal nerve roots by medication and decompression surgery may improve the supply of blood flow to the lower leg in patients with lumbar spinal stenosis.
Adult ; Aged ; Aged, 80 and over ; Alprostadil/therapeutic use ; *Ankle Brachial Index ; Decompression, Surgical/methods ; Female ; Humans ; Low Back Pain/drug therapy/physiopathology/surgery/*therapy ; Lumbar Vertebrae/physiopathology/*surgery ; Male ; Middle Aged ; Pain/surgery ; Spinal Nerve Roots/physiopathology ; Spinal Stenosis/physiopathology/*surgery/*therapy ; Treatment Outcome

Aim: To describe the current use of percutaneous endoscopic gastrostomy (PEG) in long-term care national health insurance facilities (special nursing homes for the elderly, health service facilities for the elderly, and long-term health care facilities), and assess whether its prevalence increased or not between 2007 and 2010. Methods: Based on data from the "Survey of Institutions and Establishments for Long-term Care" by the Ministry of Health, Labour and Welfare, we calculated the prevalence of residents with PEG in each type of long-term care facility in 2007 and 2010. Results: The prevalence of residents with PEG in 2007 versus 2010 was 5.8% versus 8.1% in special nursing homes for the elderly, 3.9% versus 5.9% in health service facilities for the elderly, and 18.4% versus 26.1% in long-term health care facilities. Among residents requiring level 3 or higher care, the prevalence of PEG increased in all three types of long-term care facility. Conclusion: From 2007 to 2010, the use of PEG increased among residents of long-term care facilities requiring level 3 or higher care.

Objective: We investigated the relation between fasting insulin (FI) and risk of cerebral infarction in a Japanese general population. Methods: The subjects were 2,610 men and women without past history of stroke or myocardial infarction and under treatment for diabetes, examined between 1992 and 1995 as part of the Jichi Medical School Cohort Study. The FI level was measured once at the baseline. Subjects were divided into quintiles by FI levels, and Cox’s proportional hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cerebral infarction. Results: During an average of 11.1 years of follow-up, 87 participants developed cerebral infarction. Crude incidence rates of FI quintiles 1-5 were 4.69, 2.35, 1.85, 2.77 and 3.30 per 1,000 person-years, respectively. The multivariate-adjusted HRs for cerebral infarction were 2.33 (95% CI, 1.10 – 4.96) in quintile 1 (Q1), 1.25 (95% CI, 0.55 – 2.84) in Q2, 1.68 (95% CI, 0.76 – 3.70) in Q4 and 2.06 (95% CI, 0.94 – 4.47) in Q5, using Q3 as the reference. Conclusions: The lowest FI level was associated with increased risk of cerebral infarction and the association between FI and risk of cerebral infarction appeared to be a U-shaped relationship.

Background: Helicobacter pylori (H. pylori) infection has been reported to be associated with cardiovascular risk factors by inducing chronic low-grade inflammation and by influencing endocrine and metabolic systems, as well as the immunological response evoked by the host. This study investigated the association between H. pylori infection and high density lipoprotein cholesterol (HDL-C) in Japanese subjects.
Methods: The study subjects were 2,632 (1,061 men and 1,571 women) living in rural areas in Japan. We checked H. pylori serum immunoglobulin G (IgG), HDL-C and other cardiovascular risk factors in 1999.
Results: The overall prevalence of H. pylori seropositivity was 53.5% and increased with age. The prevalence was higher among men (58.3%) than women (50.3%). H. pylori seropositive women were more associated with decreased HDL-C than seronegative subjects (58.1±13.6 vs. 60.5±14.7, p<0.01). Multiple linear regression analysis with H. pylori seropositivity, age, body mass index (BMI), fibrinogen, blood glucose, and smoking and alcohol habits demonstrated that H. pylori seropositivity was a significant predictor of decreased HDL-C in women. In addition, there was a linear decrease in HDL-C with increments in the value of H. pylori antibody titer as a continuous variable in women. This association remained in H. pylori seropositive women aged ≥50 years. Moreover, H. pylori seropositive women with BMI <22 were associated with decreased HDL-C, whereas the association was not significant in women with BMI ≥22.
Conclusions: We show that H. pylori seropositivity is associated with decreased HDL-C, especially in women with a lower BMI in rural areas of Japan.

Abstract
Objective : To investigate the causes of fever of inpatients hospitalized in the Department of General Practice at Jichi Medical University Hospital.
Methods : We reviewed all medical records of the patients hospitalized in the Department of General Practice at this hospital between April 2003 and March 2004. Patients were selected as the “febrile group” by following criteria, 1) body temperature exceeded 37.5°C on admission, 2) fever and fever of unknown origin (FUO) were included in the clinical problems, and the causes of fever were described.
Results : A total of 464 patients were hospitalized and 221 patients (47.6%) were categorized as the “febrile group”. The most common cause of fever was infection (67.4%), followed by malignant disease (4.1%), collagen disease (3.2%), miscellaneous diseases (10.4%). 26 patients were classified as fever of unknown origin (FUO). Among FUO patients, collagen disease was the most common cause (34.6%), and undiagnosed cases was 26.9% that was similar to past reports. Although the rates of malignant disease and collagen disease were about sixteen percent in each generation from thirties to fifties as the cause of fever, only one patient met the criteria of classical FUO.
Conclusions : The most common cause of fever was infection. Systematic survey including hospitalization is needed early in case an outpatient doesn't cure fever unexpectedly. Noninfectious inflammatory diseases emerge as an important category of the causative disease of FUO.

Objective : To analyze and reveal the contents of medical questionnaires distributed to nationwide general practice outpatients prior to their initial medical consultations.
Method : An observational study was conducted, based on questionnaire format. Sample questionnaires were collected from 85 hospitals registered with the Japan Primary Care Association.
Results : No standard format was found among the samples. A4 size forms (210 mm×297 mm) averaging 19.7 questions were in the majority, accounting for 68%. The distribution frequency of questionnaires reported by research cooperation centers listed 28 items (31.8%) concerning medical history, 19 items (21.6%) related to lifestyle, and 7 items (8.0%) referring to social and reproductive status.
Conclusion : This research assessed the qualitative value of medical questionnaires used in General Practice Clinics in Japan. The results indicate the nature of the medical information required by physicians prior to medical consultation.