The effect of aerobic exercise on physical function and mental health in various adult age groups (young-old, 65-74; old-old, 75-84; oldest-old, ≥ 85 years) is unclear. The aim of this study was to investigate the effects of the Kohzuki Exercise Program (KEP) on physical function and mental health in these age groups. The KEP consisted of 40-min supervised sessions 3 times per week for 6 months as follows: 5 min of warm-up, 30 min of lower limb aerobic exercise, and 5 min of cool-down. A total of 50 participants (22 young-old, 20 old-old, and 8 oldest-old) who participated in the KEP completed at least 88% of the sessions. In statistical analysis, 3 (group: oldest-old, old-old, young-old) × 2 (time: baseline and after 6 months) analyses of variance were used to determine if there were significant main and interaction effects. Significant interactions were probed using the post-hoc paired t test. The Short Physical Performance Battery (SPPB) score showed significant group × time interactions after 6 months (p = 0.031). In the post-hoc test, oldest-old (p < 0.001), old-old (p < 0.001), and young-old (p < 0.01) groups had significantly better physical function after 6 months. However, none of the mental health measures showed group × time interactions at 6-month. Our results suggest that a 6-month KEP led to improved physical function in oldest-old, old-old, and young-old adults. The KEP was effective for oldest-old adults in particular. The KEP exhibits good adherence, making it suitable for a wide age range in society.

Japan was struck by two catastrophic disasters on March 11, 2011 and on April 16, 2016. The former was the Great East Japan Earthquake (M9.0) and the latter was the Kumamoto Earthquake (M7.0). Most inhabitants in the affected areas of both disasters were forced to live in evacuation centers right after the earthquake. Poor oral hygiene, inactivity, malnourishment, appetite loss, eating problems, and swallowing problems due to lack of support for frail, disabled, or elderly evacuees occur during the early phases after a disaster. Disaster-related sequelae, such as pneumonia and disuse syndrome, may also occur as a result of inappropriate nutritional and physical support. Adequate oral intake and physical activity are important to the quality of life for evacuees. We learned lessons from our experiences of evacuee support after the two disasters, focused on feeding support, which consisted of nutritional and physical care. Our experiences revealed that more rapid intervention is necessary, particularly for frail, disabled, or elderly people. In this study, based on our experiences from the two dreadful disasters in Japan, we propose a new concept of medical assistance after a disaster, the Disaster Feeding Support Team (D-FST). The D-FST is composed of multidisciplinary professionals and provides comprehensive nutritional, physical, and health support. The D-FST also performs interventions for swallowing exercises, activity, health condition, and cognition that are related to eating circumstances. We suggest that D-FSTs are organized nationwide and initiate support activities immediately after the onset of a disaster.

Bronchial asthma (BA) is a chronic inflammatory disorder of airways for which the effective therapies include inhaled corticosteroids (ICS) and short-acting β2-adrenoreceptor agonist (SABA). Serum eosinophil cationic protein (ECP) has been reported to reflect the degree of airway inflammation. We, therefore, explored the implication of serum ECP in assessing the efficacy of ICS therapy in BA children. Our prospective randomized control study enrolled 126 BA children and 78 healthy children (the control group). The BA patients were randomly assigned as two groups; 59 children were treated with ICS, twice a day, for three months and 67 patients received SABA inhalation only if necessary. After the 3-month therapy, the serum levels of ECP, endothelin-1, and nitric oxide and the eosinophil percentage (EOS%) in induced sputum were significantly lower in the ICS group, compared with the SABA group, but were still higher than the control group (all P < 0.05). The forced expiratory volume (FEV1%pred) and forced vital capacity (FEV1/FVC) were improved to the levels of the control group after therapy. Pearson correlation analysis presented that higher serum ECP levels were associated with higher EOS% in serum and with lower pulmonary function indices (FEVl%pred and FEV1/FVC). Importantly, the ICS group exhibited higher quality of life scores and lower symptom scores compared with the SABA group (all P < 0.05). ROC results revealed the diagnostic efficiency of serum ECP levels on the efficacy of ICS. In conclusion, measuring serum ECP levels is helpful for assessing the efficacy of ICS therapy in BA children.

Cardiovascular morbidity is the leading cause of death in dialysis patients and many risk factors have been involved in its pathogenesis. Genetic susceptibility may be of importance including polymorphism for matrix metalloproteinase 3 (MMP3), which is an enzyme that catalyzes the degradation of collagen, proteoglycans, fibronectin, laminine and elastin. The MMP3 gene promoter contains an insertion/deletion polymorphism characterised by an array of 5 or 6 adenosine residues (5A/6A) at -1612 position. Literature data show that the 5A or 6A allele of the MMP3 gene shows different risk for cardiovascular and overall outcome in general population. The aim was to analyze the -1612 5A/6A promoter polymorphism in a group of hemodialysis patients and to correlate the findings with cardiovascular morbidity and 7-year all-cause and cardiovascular mortality. This study included 196 patients on hemodialysis for longer than six months at University Medical Center Zvezdara. The leading causes of end stage renal disease were hypertension and diabetes mellitus. Venous blood was collected on midweek dialysis session and genotype analysis was performed by using polymerase chain reaction-restriction fragment length polymorphism method. Among the 198 hemodialysis patients, there were 142 (72%) 5A/6A heterozygotes, 12 (6%) 5A/5A homozygotes, and 44 (22%) 6A/6A homozygotes. These data are consistent with Hardy-Weinberg equilibrium. After 7-year follow-up, the 5A homozygotes showed the lowest all-cause and cardiovascular survival, while the 6A homozygotes showed the highest cardiovascular survival. The 5A allele of the MMP3-gene promoter polymorphism is a potential risk factor in the poor outcome of hemodialysis patients.

Patients with chronic kidney disease (CKD) have markedly increased rates of major adverse cardiovascular and cerebrovascular events (MACCEs) and mortality. Therefore, identifying early biomarkers predicting clinical outcomes in patients with CKD is critical. We aimed to determine whether osteoglycin, a basic component of the vascular extracellular matrix, was associated with MACCEs or all-cause mortality, using data from a prospective randomized controlled study, K-STAR (Kremezin STudy Against Renal disease progression in Korea: NCT 00860431). A total of 383 patients (mean age: 56.4 years, men/women = 252/131) with CKD stage 3 to 4 from the original trial were enrolled in the present study. We measured serum osteoglycin level and examined the impact of osteoglycin on clinical outcomes. The mean value of osteoglycin levels was 13.3 ± 9.4 ng/mL (healthy control: 5.3 ± 2.1 ng/mL). In multivariable analysis, lower levels of proteinuria and hemoglobin and higher levels of C-reactive protein were significantly associated with higher osteoglycin levels. Estimated glomerular filtration rate was not related to osteoglycin level. During a mean follow-up period of 56 months, 25 deaths, 61 MACCEs, and 76 composite outcomes (all-cause mortality or MACCEs) occurred. In the non-diabetic group, each 1-ng/mL increase in serum osteoglycin was associated with all-cause mortality and composite outcome (hazard ratio [HR] = 1.058, P = 0.031; HR = 1.041, P = 0.036). However, osteoglycin levels were not associated with mortality, MACCEs, or composite outcome in the diabetic group. Our results indicate that serum osteoglycin is a potential predictor of adverse outcomes in patients with CKD.

Cholangiocarcinoma represents the second most common primary liver tumor after hepatocellular carcinoma. Mahanine, a carbazole alkaloid derived from Murraya koenigii (Linn.) Spreng, has been used as folk medicine in Thailand, where the liver fluke-associated cholangiocarcinoma is common. The expression of microphthalmia-associated transcription factor (MITF) is maintained at immunohistochemically undetectable levels in hepatocytes and cholangiocytes. To explore the regulation of MITF expression in the liver, we immunohistochemically analyzed the MITF expression using hepatocellular carcinoma and cholangiocarcinoma specimens of the human liver cancer tissue array. MITF immunoreactivity was detected in subsets of hepatocellular carcinoma (6 out of 38 specimens; 16%) and cholangiocarcinoma (2/7 specimens; 29%). Moreover, immunoreactivity for glioma-associated oncogene 1 (GLI1), a transcription factor of the Hedgehog signaling pathway, was detected in 55% of hepatocellular carcinoma (21/38 specimens) and 86% of cholangiocarcinoma (6/7 specimens). Importantly, MITF was detectable only in the GLI1-positive hepatocellular carcinoma and cholangiocarcinoma, and MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. Subsequently, the effect of mahanine was analyzed in HepG2 human hepatocellular carcinoma and HuCCT1 and KKU-100 human cholangiocarcinoma cells. Mahanine (25 µM) showed the potent cytotoxicity in these hepatic cancer cell lines, which was associated with increased expression levels of MITF, as judged by Western blot analysis. MITF is over-expressed in subsets of hepatocellular carcinoma and cholangiocarcinoma, and detectable MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. MITF expression levels may be determined in hepatic cancer cells by the balance between the Hedgehog signaling and the cellular stress.

Thymidylate synthase (TS) is essential in thymidylate biosynthesis and DNA replication. Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme in pyrimidine catabolism and is important in catabolism of 5-fluorouracil (5-FU). The significance of TS and DPD expressed in lung cancer remains controversial. Here we analyzed the relationship between TS and DPD expression and clinicopathological features of lung cancer. Enzyme-linked immunosorbent assays (ELISAs) were used to measure TS and DPD levels in paired tumor and non-tumor lung tissues obtained from 168 patients (107 adenocarcinomas, 39 squamous cell carcinomas, and 22 others), who had operations at the Shinshu University Hospital from 2004 to 2007 and were followed up for a median of 57.0 months. TS and DPD expression levels were higher in tumor tissues, and TS expression levels were significantly lower in adenocarcinomas than those in other subtypes. In addition, patients with low TS levels survived longer compared with patents with high TS levels. By contrast, DPD expression levels were not correlated with overall patient survival. Importantly, patients with low TS and DPD levels exhibited significantly prolonged survival than those with high TS and DPD. Among the 168 patients, 59 patients were treated with tegafur-uracil (UFT), a DPD-inhibitory fluoropyrimidine, and the UFT-treated patients with high TS and high DPD levels showed worst prognosis. Our study demonstrates a significant correlation between low TS expression levels and long-term prognosis of patients with lung cancer. Thus, ELISA is a clinically useful method to measure TS and DPD expression in lung cancer tissues.

In Korea, the prevalence of depression is increasing in adolescents and the most common cause of death of adolescents has been reported as suicide. At a time of increasing predicament of mental health of adolescents, there are few studies on whether secondhand smoking is associated with mental health in adolescents. The objective of this study was to determine whether exposure to secondhand smoke is associated with mental health-related variables, such as depression, stress, and suicide, in Korean adolescents. Data from the eleventh Korea youth risk behavior web-based survey, a nationally representative survey of 62,708 participants (30,964 males and 31,744 females), were analyzed. For students of aged 12 to 18 years, extensive data including secondhand smoking, mental health, sociodemographic variables, and physical health were collected. Chi-square analysis, multiple logistic regression analysis and ordered logistic regression analysis were performed to estimate the association and dose-response relation between secondhand smoking and mental health. Compared with the non-exposed group, the odds ratios (OR) of depression, stress, suicidal ideation, suicidal planning and suicidal attempt in the secondhand smoking exposed group were 1.339, 1.192, 1.303, 1.437 and 1.505, respectively (all P < 0.001). When subjects were classified into two secondhand smoke exposure groups, with increasing secondhand smoking experience, higher was the OR for each mental health related variable, in a dose-response relation. Our findings suggest that secondhand smoking is associated with poor mental health such as depression, stress, and suicide, showing a dose-response relation in Korean adolescents.

Atypical femoral fractures (AFFs) have been reported to occur with minimal or spontaneous subtrochanteric and femoral shaft fractures with a characteristic transverse pattern, compared with typical femoral fractures in young patients with high-energy trauma. AFFs are related to long-term use of bisphosphonates (BPs), glucocorticoids and rheumatic diseases. We have estimated a blind analysis of AFFs in rheumatic patients receiving BPs and glucocorticoids ordinary over a long time in all Yamagata prefectural area through radiographic examination. The 123 AFFs including suspected cases over six years were collected and reviewed by two independent orthopedic surgeons. We found 86 patients with a total of 99 AFFs between 2009 and 2014 (1.43 cases/100,000 person/year). Of these 99 AFFs, 11 were in 8 rheumatic patients including three patients with bilateral AFFs. The incidence of AFFs in rheumatic patients had trend to increase from 2012. The mean age of all 8 patients was 54.9 years. All 8 patients received BPs and 7/8 received prednisolone (PSL). The mean dose of PSL was 14 mg/day. Compared to patients with unilateral AFFs, those with bilateral AFFs in rheumatic patients were on a higher dose of PSL (20 mg/day vs. 7 mg/day) and had less femoral neck-shaft angle (129° vs. 136°, p < 0.05). In conclusion, the incidence of AFFs in rheumatic patients showed a trend to increase from 2012 to 2014 in Yamagata prefecture. Careful management of AFFs is of particular importance in rheumatic patients who have taken high doses of PSL and have small femoral neck-shaft angle.

We reported “Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression” in Tohoku J. Exp. Med., 2017, 241 (1), 55-63; doi: 10.1620/tjem.241.55. After publication of the paper, we have become aware of the ethical violation in collecting the samples from some patients. We therefore wish to retract the paper and apologize for any inconvenience caused by the retraction.