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*

The purpose of this study was to research the physical fitness of elderly weekly hill walkers by comparison with general average values for Japanese. The participants total 77 members (28 males and 49 females) of a mountaineering party who did a hill walking once a week for at least 1 year. The test of physical fitness consisted of muscle strength (knee extension strength, back strength, grip strength and sit ups), agility (reaction time), body flexion (long sitting forward reach), balance (one-leg balancing with eyes open) and ability of daily physical actions (10-times-reapeated sit-to-stand test and 5m maximal walking test). The general average values were taken from several previous studies considered to be highly appropriate as the general average. For statistical analysis, unpaired t-test using the number of subjects, means and standard deviations of previous studies was performed. As a result, the 4 muscle strength tests were significantly higher than the general average value (P<0.001). In addition, the agility test and 2 abilities of daily physical action’s tests were significantly faster than the general average value (P<0.001). Moreover, there was no relationship between the value of knee extension and ages, but it existed in between annual climbing number of days (male: r=0.40, P<0.05, female: r=0.35, P<0.05). In conclusion, it appears that elderly people who climb the low mountain weekly have the higher physical fitness than general average values, and it can be inferred that weekly hill walking in low mountains can potentially keep higher knee extension regardless of age.

In this report, we describe a case involving a 34-year-old woman who showed good treatment outcomes with long-term stability after multidisciplinary treatment for unilateral cleft lip and palate (CLP), maxillary hypoplasia, severe maxillary arch constriction, severe occlusal collapse, and gingival recession. A comprehensive treatment approach was developed with maximum consideration of strong scar constriction and gingival recession; it included minimum maxillary arch expansion, maxillary advancement by distraction osteogenesis using an internal distraction device, and mandibular setback using sagittal split ramus osteotomy. Her post-treatment records demonstrated a balanced facial profile and occlusion with improved facial symmetry. The patient's profile was dramatically improved, with reduced upper lip retrusion and lower lip protrusion as a result of the maxillary advancement and mandibular setback, respectively. Although gingival recession showed a slight increase, tooth mobility was within the normal physiological range. No tooth hyperesthesia was observed after treatment. There was negligible osseous relapse, and the occlusion remained stable after 5 years of post-treatment retention. Our findings suggest that such multidisciplinary approaches for the treatment of CLP with gingival recession and occlusal collapse help in improving occlusion and facial esthetics without the need for prostheses such as dental implants or bridges; in addition, the results show long-term post-treatment stability.
Adult ; Cicatrix ; Cleft Lip* ; Constriction ; Dental Implants ; Esthetics ; Female ; Gingival Recession* ; Humans ; Hyperesthesia ; Lip ; Osteogenesis, Distraction* ; Osteotomy, Sagittal Split Ramus* ; Palatal Expansion Technique ; Palate* ; Prostheses and Implants ; Recurrence ; Tooth ; Tooth Mobility

Japan has faced problems of declining birth rate and aging. Acupuncture has gained popularity among the various complementary medicines available and many go privately to have acupuncture while undergoing in vitro　fertilization(IVF). Although acupuncture has gained increasing popularity in the management of infertility, its effectiveness has remained controversial.Whether it is benetifical in terms of improvimg the live birth rate in IVF still remains subject to further well constructed randomized controlled studies.　Obesity, defined as an excess of body fat, is a growing public health crisis that is associated with the development of many disorders, including type 2 diabetes and cardiovascular disease . Menopause causes a deterioration of lipid metabolism and increases the tendency to obesity. Ovariectomized mice have been used to study changes in postmenopause metabolism and reported to gain weight due to changes in lipid metabolism, as do menopausal women. Alzheimer's disease is associated with the unprecedented aging tendency in　our world population and has become a significant health issue. In addition to a rapid acceleration of the aging progress, Alzheimer's disease is a severe affliction in patients and a heavy burden on their families and society.　Prevention of obesity and Alzheimer's disease becomes a largest matter of concern not only for medicine but also for health economics.We conclude that the partnership between acupuncture and conventional medicine is an effective treatment for obesity and Alzheimer's disease.

In Japan, Nordic walking (NW) has two style walking method. For one thing, the poles are used to push against the ground towards the back of the body (diagonal style: DIA). The other one, the poles put on forward and using like a cane (defensive style: DEF). This study aims to clarify differences between the two Nordic walking (NW) styles. The subjects were 12 community-dwelling middle-aged and older adults (mean age: 62.4 ± 7.8 years). All of subjects were tested to perform NW in both style for 12 minutes walking around the park. Walking distance, speed, heart rate (HR), energy expenditure (EE) and electromyogram (EMG) amplitude of the upper and lower limbs using surface EMG were assessed. A pole with a built-in load cell measured force used to push the pole into the ground (pole force), pole contact time, and pole impulse. Distances and speed in DIA was significantly higher than DEF. Significant difference in muscle activity was observed between DIA and DEF in the triceps brachii only. EE of DEF was significantly higher than DIA. Poling force and pole impulse in DIA was significantly higher than DEF. These results indicate that when prescribing NW for health promotion, it should be done according to each characteristic in DIA or DEF.

We report a case of acute ischemic stroke involving both the anterior and posterior circulation associated with a persistent primitive trigeminal artery (PPTA), treated by endovascular revascularization for acute basilar artery (BA) occlusion via the PPTA. An otherwise healthy 67-year-old man experienced sudden loss of consciousness and quadriplegia. Magnetic resonance imaging showed an extensive acute infarction in the right cerebral hemisphere, and magnetic resonance angiography showed occlusion of the right middle cerebral artery (MCA) and BA. Because the volume of infarction in the territory of the right MCA was extensive, we judged the use of intravenous tissue plasminogen activator to be contraindicated. Cerebral angiography revealed hypoplasia of both vertebral arteries and the presence of a PPTA from the right internal carotid artery. A microcatheter was introduced into the BA via the PPTA and revascularization was successfully performed using a Merci Retriever with adjuvant low-dose intraarterial urokinase. After treatment, his consciousness level and right motor weakness improved. Although persistent carotid-vertebrobasilar anastomoses such as a PPTA are relatively rare vascular anomalies, if the persistent primitive artery is present, it can be an access route for mechanical thrombectomy for acute ischemic stroke.
Aged ; Arteries* ; Basilar Artery* ; Carotid Artery, Internal ; Cerebral Angiography ; Cerebrum ; Consciousness ; Humans ; Infarction ; Magnetic Resonance Angiography ; Magnetic Resonance Imaging ; Middle Cerebral Artery ; Quadriplegia ; Stroke* ; Thrombectomy ; Tissue Plasminogen Activator ; Unconsciousness ; Urokinase-Type Plasminogen Activator ; Vertebral Artery

This study aimed to elucidate how body composition, force-generating capacity and jump performances are associated with 50-m sprint velocity in circumpubertal boys, in relation to sprint phases and maturation. One hundred thirty four circumpubertal boys were allocated to preadolescent or adolescent group on basis of the height at the peak height velocity of Japanese boys (154 cm) reported in literature: those with body heights over 154 cm as adolescent group and others as preadolescent group. Body composition was determined by bioelectrical impedance analysis. In addition to maximal voluntary isometric knee extension torque, the performances of counter movement jump (CMJ), rebound jump (RJ), standing long jump (SLJ) and standing 5-step jump (SFJ) were also measured. RJ-index was calculated by dividing height by contact time. The time of 50-m sprint was determined at 10-m intervals. Multiple regression analysis showed that in preadolescent boys, SFJ become a predictor for the sprint speed during acceleration phases, and SFJ, RJ-index and CMJ as predictors for the sprint speeds during maximal speed and deceleration phases. In the adolescent boys, age, CMJ, SLJ, and SFJ become a predictor for the sprint speed during acceleration phases, and torque relative to body mass, CMJ and SFJ were selected as predictors for the sprint speeds during maximal speed and deceleration phases. Thus, the current results indicate that force-generating capacity and jumping ability are determinants for sprint performance in circumpubertal boys, but the relative contribution of each of the two factors differs between preadolescent and adolescent stages and among the sprint phases.

We report an extremely rare case of primary squamous cell carcinoma of the stomach. A 69-year-old man was admitted to our hospital with a 2-month history of dysphagia and tarry stools. Endoscopic examination revealed a cauliflower-shaped protruding mass along the lesser curvature of the gastric cardia. Biopsy of the lesion revealed squamous cell carcinoma of the stomach. Computed tomography revealed a thickened stomach wall and a mass protruding into the gastric lumen. Total gastrectomy with splenectomy, distal pancreatectomy, and Roux-en-Y reconstruction was performed, together with a lower thoracic esophagectomy via a left thoracotomy. Histopathological examination of the specimen revealed well-differentiated squamous cell carcinoma of the stomach. Postoperative follow-up was uneventful for the first 18 months. However, multiple liver metastases and para-aortic lymph node metastasis developed subsequently. Despite systemic combination chemotherapy, the patient died because of progression of the recurrent tumors. Here, we review the characteristics of 56 cases of gastric squamous cell carcinoma reported in Japan.
Aged ; Biopsy ; Carcinoma, Squamous Cell* ; Cardia ; Deglutition Disorders ; Drug Therapy, Combination ; Esophagectomy ; Follow-Up Studies ; Gastrectomy ; Humans ; Japan* ; Liver ; Lymph Nodes ; Neoplasm Metastasis ; Pancreatectomy ; Splenectomy ; Stomach Neoplasms ; Stomach* ; Thoracotomy

BACKGROUND/AIMS: The gastrointestinal motility effects of endogenous incretin hormones enhanced by dipeptidyl peptidase-IV (DPP-IV) inhibitors have not yet been sufficiently investigated. The aim of this study was to determine whether single pre-prandial sitagliptin, the DPP-IV inhibitor, administration might have an effect on the rate of liquid gastric emptying using the 13C-acetic acid breath test. METHODS: Ten healthy male volunteers participated in this randomized, two-way crossover study. The subjects fasted for overnight and were randomly assigned to receive 50 mg sitagliptin 2 hours before ingestion of the liquid test meal (200 kcal per 200 mL, containing 100 mg 13C-acetate) or the test meal alone. Under both conditions, breath samples were collected for 150 minutes following the meal. Liquid gastric emptying was estimated by the values of the following parameters: the time required for 50% emptying of the labeled meal (T1/2), the analog to the scintigraphy lag time for 10% emptying of the labeled meal (Tlag), the gastric emptying coefficient and the regression-estimated constants (beta and kappa), calculated by using the 13CO2 breath excretion curve using the conventional formulae. The parameters between the 2 test conditions were compared statistically. RESULTS: No significant differences in the calculated parameters, including T1/2, Tlag, gastric emptying coefficient or beta and kappa, were observed between the 2 test conditions. CONCLUSIONS: The present study revealed that single-dose sitagliptin intake had no significant influence on the rate of liquid gastric emptying in asymptomatic volunteers.
Breath Tests ; Cross-Over Studies ; Eating ; Gastric Emptying ; Gastrointestinal Motility ; Humans ; Incretins ; Male ; Meals ; Pyrazines ; Triazoles ; Sitagliptin Phosphate

This study aimed to determine the relationships between the torque generating capacity of the lower extremity muscles and either running or jump performance in primary and junior high school boys. A total of 102 primary and junior high school boys participated in this study. Muscle thicknesses (MTs) of the knee extensors and plantar flexors were determined using ultrasonography. Muscle volumes (MVs) of the knee extensors and plantar flexors were estimated using MTs and limb lengths. The isometric joint torques (TQs) for knee extensors and ankle plantar flexors were measured using myometer. MV and TQ were divided by body mass (MV/BM and TQ/BM, respectively). Running velocity was measured using a non-motorized treadmill. The counter movement jump (CMJ) and squat jump (SJ) were performed on a matswitch system. The flight time was measured and used to calculate the heights of CMJ and SJ using the following equation; height (cm) = g × (flight time)² /8/10. As the result of multiple regression analysis, age, MV/BM and TQ/BM were selected as predictors of running velocity in the primary school boys, whereas TQ and lean body mass in junior high school boys. In the primary school boys, TQ/BM and body fat mass was selected as significant contributors for SJ and CMJ performances, whereas, in the junior high school boys, TQ and the percent of body fat for SJ performance and MV/BM and TQ for CMJ performance. Thus, the present results indicate that the relationships between torque generating capacity of the lower extremity muscles and either running or jump performance differ between primary and junior high school boys. It may be assumed that, for running and jump performances, muscle mass and strength become determinant factors in junior high school boys, whereas their values relative to body mass in primary school boys.