BACKGROUND: Our previous observational cohort study, the Kashima Scan Study (KSS), identified associations between lifestyle, cerebral small vessel disease (SVD) as detected by magnetic resonance imaging of the brain, and disease outcomes including cognitive impairment and vascular diseases. However, established modifiers of the outcomes such as genetic background, drinking and exercise habits, and socioeconomic status were not considered. Regarding genetic factors in particular, the ALDH2 rs671 variant, East Asian-specific diversity, and APOE status are expected to have strong effects. The aim of KSS-2 is to examine the interactions of genetic background, lifestyle factors including drinking habit, socioeconomic status, and/or SVD markers for cognitive impairment, vascular disease, and death. METHOD: The KSS-2 is a prospective regional observational study of a healthy Japanese cohort that will clarify lifestyle habits to better maintain brain health from midlife by genotype. Japanese adults who underwent brain health checkups at their own expense are enrolled and will be followed-up for 10 years. We will extend the protocol of the KSS to include genetic background and potential confounding factors, including lifestyle (including drinking and exercise habit) and socioeconomic status, and perform survival analyses. The study outcomes are cognitive impairment, vascular events, and death. RESULTS: We enrolled 908 healthy adults (mean age 64.2 years; range 35 to 84 years; 41% male) from September 1, 2018 until December 31, 2024. CONCLUSION This study will provide important insights into the development of individualized health intervention strategies.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Cerebral Small Vessel Diseases/diagnostic imaging* ; Japan/epidemiology* ; Life Style ; Magnetic Resonance Imaging ; Prospective Studies ; Observational Studies as Topic

Clot waveform analysis (CWA) observes changes in transparency in a plasma sample based on clotting tests such as activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Evidence indicates that not only an abnormal waveform but also peak times and heights in derivative curves of CWA are useful for the evaluation of hemostatic abnormalities. Modified CWA, including the PT with APTT reagent, dilute PT (small amount of tissue factor [TF]-induced clotting factor IX [FIX] activation; sTF/FIXa), and dilute TT, has been proposed to evaluate physiological or pathological hemostasis. We review routine and modified CWA and their clinical applications. In CWA-sTF/FIXa, elevated peak heights indicate hypercoagulability in patients with cancer or thrombosis, whereas prolonged peak times indicate hypocoagulability in several conditions, including clotting factor deficiency and thrombocytopenia. CWA-dilute TT reflects the thrombin burst, whereas clot-fibrinolysis waveform analysis reflects both hemostasis and fibrinolysis. The relevance and usefulness of CWA-APTT and modified CWA should be further investigated in various diseases.

Purpose: Most studies have investigated the differences in postgastrectomy quality of life (QOL) based on the surgical procedure or reconstruction method adopted; only a few studies have compared QOL based on tumor location. This large-scale study aims to investigate the differences in QOL between patients with esophagogastric junction cancer (EGJC) and those with upper third gastric cancer (UGC) undergoing the same gastrectomy procedure to evaluate the impact of tumor location on postoperative QOL. Methods: The Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45) questionnaire was distributed in 70 institutions to 2,364 patients who underwent gastrectomy for EGJC or UGC.A total of 1,909 patients were eligible for the study, and 1,744 patients who underwent total gastrectomy (TG) or proximal gastrectomy (PG) were selected for the final analysis. These patients were divided into EGJC and UGC groups; thereafter, the PGSAS-45 main outcome measures (MOMs) were compared between the two groups for each type of gastrectomy. Results: Among the post-TG patients, only one MOM was significantly better in the UGC group than in the EGJC group. Conversely, among the post-PG patients, postoperative QOL was significantly better in 6 out of 19 MOMs in the UGC group than in the EGJC group. Conclusions Tumor location had a minimal effect on the postoperative QOL of post-TG patients, whereas among post-PG patients, there were definite differences in postoperative QOL between the two groups. It seems reasonable to conservatively estimate the benefits of PG in patients with EGJC compared to those in patients with UGC.

A 64-year-old man was found to have a nodule in his right lung. He also complained of nausea and abdominal pain during the clinical course. Esophagogastroduodenoscopy revealed a duodenal ulcer associated with severe stenosis and a suspicion of malignancy. However, three subsequent biopsies revealed no evidence of malignancy. The fourth biopsy showed scattered large eosinophilic cells with an eccentric nucleus, leading to a diagnosis of Russell body duodenitis (RBD). RBD is an extremely rare disease, and little is known about its etiology and clinical course. The pathogenesis of RBD is discussed based on our experience with this case.
Abdominal Pain ; Biopsy ; Constriction, Pathologic ; Diagnosis ; Duodenal Ulcer ; Duodenitis* ; Endoscopy, Digestive System ; Eosinophils ; Humans ; Lung ; Middle Aged ; Nausea ; Rare Diseases

To evaluate the association of serum BDNF concentration with high-intensity interval training, 12 healthy male volunteers, aged 28-48 years, completed 16-week high-intensity interval training (HIIT) using ergometer. Training program consisted of >90% VO₂ peak for 60 sec separated by 60 sec active rest period for 8-12 sets twice weekly for 16-week. Maximal exercise tolerance tests were performed before (0-week), 4-week, and 16-week after the intervention program. VO₂ peak as well as peak watt was linearly increased after 4-week (9% for both VO₂ peak and peak watt) and 16-week HIIT training (15% for VO₂ peak and 18% for peak watt, p<0.01). However, there was no change in serum BDNF concentration by HIIT. On the other hand, there was a positive association of serum BDNF concentration at baseline with % increase in peak watt after the intervention (ρ=0.60, p<0.05). The association between BDNF and exercise training is still unclear, and more studies are needed to clarify the above positive association.

The purpose of the present study was to discuss the effects of risedronate on osteoarthritis (OA) of the knee by reviewing the existing literature. The literature was searched with PubMed, with respect to prospective, double-blind, randomized placebo-controlled trials (RCTs), using the following search terms: risedronate, knee, and osteoarthritis. Two RCTs met the criteria. A RCT (n = 231) showed that risedronate treatment (15 mg/day) for 1 year improved symptoms. A larger RCT (n = 1,896) showed that risedronate treatment (5 mg/day, 15 mg/day, 35 mg/week, and 50 mg/week) for 2 years did not improve signs or symptoms, nor did it alter radiological progression. However, a subanalysis study (n = 477) revealed that patients with marked cartilage loss preserved the structural integrity of subchondral bone by risedronate treatment (15 mg/day and 50 mg/week). Another subanalysis study (n = 1,885) revealed that C-terminal crosslinking telopeptide of type II collagen (CTX-II) decreased with risedronate treatment in a dose-dependent manner, and levels reached after 6 months were associated with radiological progression at 2 years. The results of these RCTs show that risedronate reduces the marker of cartilage degradation (CTX-II), which could contribute to attenuation of radiological progression of OA by preserving the structural integrity of subchondral bone. The review of the literature suggests that higher doses of risedronate (15 mg/day) strongly reduces the marker of cartilage degradation (CTX-II), which could contribute to attenuation of radiological progression of OA by preserving the structural integrity of subchondral bone.
Animals ; Calcium Channel Blockers/pharmacology/*therapeutic use ; Cartilage/drug effects ; Diphosphonates/therapeutic use ; Etidronic Acid/*analogs & derivatives/pharmacology/therapeutic use ; Humans ; Osteoarthritis, Knee/*drug therapy

PURPOSE: To compare the effect of vitamin K2 and risedronate on trabecular bone in glucocorticoid (GC)-treated rats. MATERIALS AND METHODS: Forty-eight Sprague-Dawley female rats, 3 months of age, were randomized by the stratified weight method into 5 groups according to the following treatment schedule: age-matched control, GC administration, and GC administration with concomitant administration of vitamin K2, risedronate, or vitamin K2 + risedronate. GC (methylprednisolone sodium succinate, 5.0 mg/kg) and risedronate (10 microgram/kg) were administered subcutaneously three and five times a week, respectively. Vitamin K2 (menatetrenone, 30 mg/kg) was administered orally three times a week. At the end of the 8-week experiment, bone histomorphometric analysis was performed on trabecular bone of the tibial proximal metaphysis. RESULTS: GC administration decreased trabecular bone mass compared with age-matched controls because of decreased bone formation (mineralizing surface, mineral apposition rate, and bone formation rate) and increased bone erosion. Vitamin K2 attenuated GC-induced trabecular bone loss by preventing GC-induced decrease in bone formation (mineralizing surface) and subsequently reducing GC-induced increase in bone erosion. Risedronate prevented GC-induced trabecular bone loss by preventing GC-induced increase in bone erosion although it also suppressed bone formation (mineralizing surface, mineral apposition rate, and bone formation rate). Vitamin K2 mildly attenuated suppression of bone formation (mineralizing surface) and bone erosion caused by risedronate without affecting trabecular bone mass when administered in combination. CONCLUSION: The present study showed differential effect of vitamin K2 and risedronate on trabecular bone in GC-treated rats.
Animals ; Bone Density/drug effects ; Bone and Bones/anatomy & histology/*drug effects/metabolism ; Etidronic Acid/*analogs & derivatives/pharmacology ; Female ; Glucocorticoids/*pharmacology ; Random Allocation ; Rats ; Vitamin K/*pharmacology ; Vitamins/*pharmacology

PURPOSE: The comparative effects of alendronate and alfacalcidol on bone mineral density (BMD) and bone turnover have already been established in postmenopausal women with osteoporosis. An open-labeled prospective study was conducted to compare the treatment effects of alendronate and alfacalcidol on hip BMD and bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures. MATERIALS AND METHODS: One hundred twelve men with osteoporosis or osteopenia with clinical risk factors for fractures (mean age: 71.4 years) were randomly divided into two groups of 56 patients each: the alendronate (5 mg daily) and alfacalcidol (1 microgram daily) groups. The BMD of the total hip, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of bone-specific alkaline phosphatase (BSAP) were measured during the 12-month-treatment period. RESULTS: Forty-five patients in the alendronate group and 42 patients in the alfacalcidol group completed the trial. Alendronate increased BMD (+2.3% at 12 months) following reductions in the urinary level of NTX (-46.4% at 3 months) and serum level of BSAP (-34.1% at 12 months), while alfacalcidol sustained BMD (-1.9% at 12 months) as well as the urinary level of NTX (+13.2% at 3 months) and serum level of BSAP (+1.8% at 12 months). CONCLUSION: The present study confirmed that alendronate has better efficacy than alfacalcidol (active control) in increasing hip BMD and reducing bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.
Aged ; Aged, 80 and over ; Alendronate/pharmacology/therapeutic use ; Asian Continental Ancestry Group ; Bone Density/*drug effects ; *Bone Density Conservation Agents/pharmacology/therapeutic use ; Bone Diseases, Metabolic/*drug therapy ; Fractures, Bone/*prevention & control ; Hip Joint/*drug effects/pathology ; Humans ; *Hydroxycholecalciferols/pharmacology/therapeutic use ; Male ; Middle Aged ; Osteoporosis/*drug therapy ; Treatment Outcome

PURPOSE: The comparative effects of alendronate and alfacalcidol on bone mineral density (BMD) and bone turnover have already been established in postmenopausal women with osteoporosis. An open-labeled prospective study was conducted to compare the treatment effects of alendronate and alfacalcidol on hip BMD and bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures. MATERIALS AND METHODS: One hundred twelve men with osteoporosis or osteopenia with clinical risk factors for fractures (mean age: 71.4 years) were randomly divided into two groups of 56 patients each: the alendronate (5 mg daily) and alfacalcidol (1 microgram daily) groups. The BMD of the total hip, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of bone-specific alkaline phosphatase (BSAP) were measured during the 12-month-treatment period. RESULTS: Forty-five patients in the alendronate group and 42 patients in the alfacalcidol group completed the trial. Alendronate increased BMD (+2.3% at 12 months) following reductions in the urinary level of NTX (-46.4% at 3 months) and serum level of BSAP (-34.1% at 12 months), while alfacalcidol sustained BMD (-1.9% at 12 months) as well as the urinary level of NTX (+13.2% at 3 months) and serum level of BSAP (+1.8% at 12 months). CONCLUSION: The present study confirmed that alendronate has better efficacy than alfacalcidol (active control) in increasing hip BMD and reducing bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.
Aged ; Aged, 80 and over ; Alendronate/pharmacology/therapeutic use ; Asian Continental Ancestry Group ; Bone Density/*drug effects ; *Bone Density Conservation Agents/pharmacology/therapeutic use ; Bone Diseases, Metabolic/*drug therapy ; Fractures, Bone/*prevention & control ; Hip Joint/*drug effects/pathology ; Humans ; *Hydroxycholecalciferols/pharmacology/therapeutic use ; Male ; Middle Aged ; Osteoporosis/*drug therapy ; Treatment Outcome

PURPOSE: To examine the influence of ovariectomy (OVX) on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites in mature cynomolgus monkeys. MATERIALS AND METHODS: Six female cynomolgus monkeys, aged 17-21 years, were randomized into 2 groups by the stratified weight: the OVX and sham-operation groups (n = 3 in each group). The experimental period was 16 months. Lumbar bone mineral density (BMD) in vivo and serum and urinary bone turnover markers were longitudinally measured, and peripheral quantitative computed tomographic and bone histomorphometric analyses were performed on trabecular bone of the lumbar vertebra, femoral neck, and distal radius at the end of the experiment. RESULTS: OVX induced in a reduction in lumbar BMD compared with the sham controls and the baseline, as a result of increased serum levels of bone-specific alkaline phosphatase and urinary levels of cross-lined N- and C-terminal telopeptides of type I collagen. Furthermore, OVX induced reductions in trabecular volumetric BMD and trabecular bone mass compared with the sham controls, with increased bone formation rate at the lumbar vertebra, femoral neck, and distal radius. CONCLUSION: The results indicated that OVX in mature cynomolgus monkeys (17-21 years of age) increased bone turnover and induced trabecular bone loss at the three skeletal sites compared with the sham controls. Thus, mature cynomolgus monkeys could be utilized for preclinical studies to examine the effects of interventions on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites.
Alkaline Phosphatase/blood ; Animals ; *Bone Density ; Collagen Type I/urine ; Female ; Femur Neck/metabolism ; Lumbar Vertebrae/metabolism ; Macaca fascicularis/*physiology ; Ovariectomy/*adverse effects ; Radius/metabolism ; Random Allocation