Gender differences in risk factors for the 2 year development of sarcopenia in community-dwelling older adults.

BACKGROUND: Sarcopenia is an age-related chronic condition that can lead to mobility disabilities. This study aimed to evaluate the risk factors for incident sarcopenia in older Korean adults. METHODS: The Korean Frailty and Aging Cohort Study (KFACS) is a multicentre prospective study with a baseline examination in 2016-2017. A prospective follow-up study was conducted in 2018-2019. Changes in muscle-related variables were evaluated for subjects aged 70-84 years lacking sarcopenia at baseline. Sarcopenia was diagnosed according to the 2019 updated Asian Working Group for Sarcopenia consensus. RESULTS: Among the 1636 participants (54.4% women, age 75.9 ± 3.7) who did not have sarcopenia at baseline, 101 men (13.5%) and 104 women (11.7%) developed sarcopenia by the follow-up. Those who developed sarcopenia were older (men, 77.9 ± 3.9 vs. 75.7 ± 3.5, P < 0.001; women, 77.5 ± 4.0 vs. 75.5 ± 3.6, P < 0.001) with a lower body mass index at baseline (men, 23.9 ± 2.4 vs. 24.5 ± 2.9 kg/m2 , P = 0.025; women, 23.7 ± 2.8 vs. 25.2 ± 2.9 kg/m2 , P < 0.001) compared with older adults who remained nonsarcopenic; levels of glycated haemoglobin (men, 6.2 ± 1.0% vs. 5.9 ± 0.8%, P = 0.029) and the homeostasis model assessment of insulin resistance (men, 2.0 ± 1.3 vs. 1.7 ± 1.2, P = 0.022) were higher in men who progressed to sarcopenia but not in women. Development of sarcopenia was associated with older age and the frequency of resistance training (≥2 per week) after adjusting for potential risk factors in men [age, odds ratio (OR) 1.17, 95% confidence interval (CI) 1.10-1.25; frequent resistance training, OR 0.50, 95% CI 0.30-0.82]. In women, advanced age, poor nutritional status, and physical inactivity contributed to the development of sarcopenia (age, OR 1.14, 95% CI 1.08-1.21; mini nutritional assessment short form, OR 0.79, 95% CI 0.70-0.90; moderate to high physical activity, OR 0.57, 95% CI 0.34-0.95). CONCLUSIONS: In this 2 year KFACS follow-up, modifiable risk factors for incident sarcopenia differed between genders. Resistance training (≥2 per week) helped to prevent sarcopenia in these community-dwelling older men. In older women, adequate nutritional support and being physically active might play a role in preventing progression to sarcopenia.

Post-stroke Hyperglycemia in Non-diabetic Ischemic Stroke is Related With Worse Functional Outcome: A Cohort Study.

OBJECTIVE: To investigate long-term and serial functional outcomes in ischemic stroke patients without diabetes with post-stroke hyperglycemia. METHODS: The Korean Stroke Cohort for Functioning and Rehabilitation (KOSCO) is a large, multi-center, prospective cohort study of stroke patients admitted to participating hospitals in nine areas of Korea. From KOSCO, ischemic stroke patients without diabetes were recruited and divided into two groups: patients without diabetes without (n=779) and with post-stroke hyperglycemia (n=223). Post-stroke hyperglycemia was defined as a glucose level >8 mmol/L. Functional assessments were performed 7 days and 3, 6, and 12 months after stroke onset. RESULTS: There were no significant differences in baseline characteristics between the groups, except in the age of onset and smoking. Analysis of the linear correlation between the initial National Institutes of Health Stroke Scale (NIHSS) score and glucose level showed no significant difference. Among our functional assessments, NIHSS, Fugl-Meyer Assessment (affected side), Functional Ambulatory Category, modified Rankin Scale, and Korean Mini-Mental State Examination (K-MMSE) showed statistically significant improvements in each group. All functional improvements except K-MMSE were significantly higher in patients without post-stroke hyperglycemia at 7 days and 3, 6, and 12 months. CONCLUSION: The glucose level of ischemic stroke patients without diabetes had no significant correlation with the initial NIHSS score. The long-term effects of stress hyperglycemia showed worse functional outcomes in ischemic stroke patients without diabetes with post-stroke hyperglycemia.

Effect of regular swimming exercise to duration-intensity on neurocognitive function in cerebral infarction rat model.

Objective: This study investigated the effect of regular swimming exercise according to the duration-intensity on neurocognitive function in a cerebral infarction rat model. Methods: Forty male Sprague-Dawley 10-week-old rats, weighing 300 ± 50 g, were subjected to photothrombotic cerebral infarction. The remaining 36 rats were randomly divided into four groups (n = 9 per group: non-exercise (group A); swimming exercise of short duration-intensity (5 min/day, group B); swimming exercise of moderate duration-intensity (10 min/day, group C); and swimming exercise of long duration-intensity (20 min/day, group D). Exercise was performed five times a week for 4 weeks, beginning the day after cerebral infarction. Neurocognitive function was evaluated with the Morris water maze test. Immunohistochemistry and western blot analysis examined brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) at 4 weeks postinfarction. Results: At 4 weeks postinfarction, escape latency was found to be shorter in group C than in any of groups A, B, or D. Immunohistochemistry revealed the most significant immunoreactivity for BDNF and VEGF in group C. Western blot analysis demonstrated that BDNF and VEGF proteins were markedly expressed in group C. Conclusions: Regular swimming exercise of moderate duration-intensity may be the most effective exercise protocol for the recovery of neurocognitive function in cerebral infarction rat model.

Prostaglandin E2 stimulates urokinase-type plasminogen activator receptor via EP2 receptor-dependent signaling pathways in human AGS gastric cancer cells.

Aberrant expression of urokinase-type plasminogen activator receptor (uPAR) has been observed in human gastric cancers. Prostaglandin E2 (PGE2 ), whose biosynthesis is catalyzed by cyclooxygenase-2 (COX-2), is implicated in cancer metastasis; however, the cellular and molecular mechanisms of PGE2 -driven uPAR expression are yet to be elucidated in human gastric cancer AGS cells. In this study, we showed that PGE2 induces uPAR expression in concentration- and time-dependent manners. Furthermore, using antagonists and siRNA, we found that among the four subtypes of PGE2 receptors, EP2 receptors are involved in PGE2 -induced uPAR expression. PGE2 induced the activation of Src, epidermal growth factor receptor (EGFR), c-Jun NH2 -terminal kinase (JNK), extracellular signal-regulated kinase (Erk), and p38 mitogen activated protein kinase (p38 MAPK). Specific inhibitor and mutagenesis studies showed that Src, EGFR, JNK1/2, and Erk1/2 are involved in PGE2 -induced uPAR expression. PGE2 induces EP2-dependent phosphorylation of Src, while the activation of Src-dependent EGFR leads to the phosphorylation of JNK1/2 and Erk1/2. Deletion and site-directed mutagenesis studies demonstrated the involvement of transcription factor activator protein (AP)-1 and nuclear factor-kappa B (NF-κB) in PGE2 -induced uPAR expression. EGFR-dependent MAPKs (JNK1/2 and Erk1/2) function as the upstream signaling molecules in the activation of AP-1 and NF-κB, respectively. AGS cells pre-treated with PGE2 showed remarkably enhanced invasiveness, which was partially abrogated by uPAR-neutralizing antibodies. To the best of our knowledge, this is the first report that PGE2 -induced uPAR expression, which stimulates invasiveness of human gastric cancer AGS cells, is mediated by the EP2 receptor-dependent Src/EGFR/JNK1/2, Erk1/2/AP-1, and Src/EGFR/JNK1/2, Erk1/2/NF-κB cascades. © 2016 Wiley Periodicals, Inc.

Neurorestorative effects of epigallocatechin-3-Gallate on cognitive function in a chronic cerebral hypoperfusion rat model.

PURPOSE: This study investigated whether (-)-epigallocatechin-3-gallate (EGCG) can enhance cognition by a neurorestorative effect in a rat model of bilateral common carotid artery occlusion (BCCAO). METHODS: Forty-eight male, 8-week-old Sprague-Dawley rats were randomly allocated to four groups 6 weeks after BCCAO or sham operation: EGCG-single intravenous injection (25 mg/kg/day; SIV group), EGCG-multiple intraperitoneal injection (50 mg/kg/day for 5 days; MIP group), untreated BCCAO group (untreated group), and sham-operated group (sham group). RESULTS: Escape latency was significantly shorter in the SIV and MIP groups than in the untreated group. SIV and MIP groups were significantly different from the untreated group in the activity of superoxide dismutase and the content of malondialdehyde (p < 0.05). Protein expression level of brain-derived neurotrophic factor was not significantly different between groups (p > 0.05), while protein expression of vascular endothelial growth factor was significantly lower in the SIV group than in the untreated group (p < 0.05). Protein expression of N-methyl-D-aspartate receptor subunits NR1 and NR2B was significantly higher in the MIP group than in the untreated group (p < 0.05). CONCLUSIONS: EGCG administration at 6 weeks after BCCAO is neurorestorative via an anti-oxidant effect and synaptogenesis, except for angiogenesis.

Chronic Kidney Disease and Functional Outcomes 6 Months after Ischemic Stroke: A Prospective Multicenter Study.

BACKGROUND: The aim of this study was to investigate whether chronic kidney disease (CKD) predicts the outcome of the Functional Independence Measure (FIM) and the Korean version of the modified Barthel Index (K-MBI) 6 months after stroke with adjustment for age, gender, education, smoking, drinking, obesity, hypertension, diabetes mellitus, dyslipidemia, the FIM or K-MBI at discharge and the National Institutes of Health Stroke Scale (NIHSS) score 7 days post stroke. METHODS: This study is an interim report of the Korean Stroke Cohort for Functioning and Rehabilitation. The sample included 2,037 ischemic stroke patients aged 18 years or older. The FIM and K-MBI scores were assessed at discharge and at 6 months after the onset of stroke. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. CKD was defined as an eGFR <60 ml/min/1.73 m2. RESULTS: Overall, the mean age was 65.5 (±12.4) years. The proportion of men was 62.6%. The proportion of CKD cases was 12.7%. The means of the 6-month FIM and K-MBI were 109.8 (±27.9) and 87.0 (±26.4), respectively. In multiple linear regressions, the 6-month FIM after stroke was significantly associated with CKD (-2.85, p < 0.05), age (-0.29, p < 0.01), the FIM at discharge (0.46, p < 0.01) and the 7-day NIHSS score (-1.71, p < 0.01). Additionally, the post-stroke 6-month K-MBI was significantly associated with CKD (-2.88, p < 0.01), age (-0.27, p < 0.01), the K-MBI at discharge (0.46, p < 0.01) and the 7-day NIHSS score (-1.55, p < 0.01). CONCLUSIONS: This nationwide hospital-based cohort study showed that CKD might predict poor 6-month FIM and K-MBI scores in ischemic stroke patients.

Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery.

BACKGROUND: Since cancer cells are normally over-expressed cathepsin B, we synthesized dendrimer-methoxy poly(ethylene glycol) (MPEG)-doxorubicin (DOX) conjugates using a cathepsin B-cleavable peptide for anticancer drug targeting. METHODS: Gly-Phe-Leu-Gly peptide was conjugated with the carboxylic acid end groups of a dendrimer, which was then conjugated with MPEG amine and doxorubicin by aid of carbodiimide chemistry (abbreviated as DendGDP). Dendrimer-MPEG-DOX conjugates without Gly-Phe-Leu-Gly peptide linkage was also synthesized for comparison (DendDP). Nanoparticles were then prepared using a dialysis procedure. RESULTS: The synthesized DendGDP was confirmed with (1)H nuclear magnetic resonance spectroscopy. The DendDP and DendGDP nanoparticles had a small particle size of less than 200 nm and had a spherical morphology. DendGDP had cathepsin B-sensitive drug release properties while DendDP did not show cathepsin B sensitivity. Further, DendGDP had improved anticancer activity when compared with doxorubicin or DendDP in an in vivo CT26 tumor xenograft model, ie, the volume of the CT26 tumor xenograft was significantly inhibited when compared with xenografts treated with doxorubicin or DendDP nanoparticles. The DendGDP nanoparticles were found to be relatively concentrated in the tumor tissue and revealed stronger fluorescence intensity than at other body sites while doxorubicin and DendDP nanoparticles showed strong fluorescence intensity in the various organs, indicating that DendGDP has cathepsin B sensitivity. CONCLUSION: DendGDP is sensitive to cathepsin B in tumor cells and can be used as a cathepsin B-responsive drug targeting strategy. We suggest that DendGDP is a promising vehicle for cancer cell targeting.

Smart Nanoparticles Based on Hyaluronic Acid for Redox-Responsive and CD44 Receptor-Mediated Targeting of Tumor.

BACKGROUND: Since aggressive cancer cells highly express the CD44 receptor compared to normal cells, hyaluronic acid (HA) can be used for CD44 targeting molecule. Since glutathione (GSH) level is normally elevated in the intracellular compartment and in the tumor cell, the fact that disulfide bond can be cleaved by GSH is widely used for intracellular drug delivery. METHODS: HA was connected with poly(DL-lactide-co-glycolide) (PLGA) using disulfide linkage, and then a diblock copolymer (HAssLG) was prepared. Doxorubicin (DOX)-loaded HAssLG nanoparticles were prepared by dialysis procedures. RESULTS AND DISCUSSION: DOX-loaded HAssLG nanoparticles have spherical shapes with small particle size of less than 300 nm. In fluorescence measurement, DOX was dose-dependently liberated from nanoparticles by the addition of GSH. DOX release rate from HAssLG nanoparticles was increased by the addition of GSH. To confirm CD44 receptor-mediated endocytosis of nanoparticles, CD44-positive MDA-MB231 cells were employed and fluorescence intensity was strong when nanoparticles were treated to tumor cells. However, fluorescence intensity was significantly decreased through blocking of the CD44 receptor by pretreatment of cells with free HA. Fluorescence intensity of cells was increased again when GSH was added, indicating that HAssLG nanoparticles have CD44 receptor targetability and potential of redox-responsive drug delivery. For animal imaging study, CD44-positive MDA-MB231 cells and CD44-negative NIH3T3 cells were simultaneously implanted into the right flank and left flank of mice, respectively. Fluorescence intensity was significantly stronger at tumor mass of MDA-MB231 cells than solid mass of NIH3T3 cells, indicating that HAssLG nanoparticles were specifically delivered to tumor cells. CONCLUSIONS: The results indicated that HAssLG nanoparticles have specificity against the CD44 receptor and can be used for anticancer drug targeting. We recommend HAssLG nanoparticles as a promising vehicle for cancer drug targeting.

Korean Brain Rehabilitation Registry for rehabilitation of persons with brain disorders: annual report in 2009.

This first annual report provides a description of patients discharged from rehabilitation facilities in Korea based on secondary data analysis of Korean Brain Rehabilitation Registry V1.0 subscribed in 2009. The analysis included 1,697 records of patients with brain disorders including stroke, traumatic brain injury, brain tumor and other disorders from 24 rehabilitation facilities across Korea. The data comprised 1,380 cases of stroke, 104 cases of brain injury, 55 cases of brain tumor, and 58 cases of other brain diseases. The functional status of each patient was measured using the Korean version of the Modified Barthel Index (KMBI). The average change in the KMBI score was 15.9 for all patients in the inpatient rehabilitation facility. The average length of stay for inpatient rehabilitation was 36.9 days. The transfer rates to other hospitals were high, being 62.4% when all patients were considered. Patients with brain disorders of Korea in 2009 and measurable functional improvement was observed in patients. However, relatively high percentages of patients were not discharged to the community after inpatient rehabilitation. Based on the results of this study, consecutive reports of the status of rehabilitation need to be conducted in order to provide useful information to many practitioners.

Therapeutic experience on multiple contractures in sclerodermoid chronic graft versus host disease.

INTRODUCTION: A 25-year-old male underwent allogenic peripheral blood stem cell transplantation and developed sclerodermoid chronic graft versus host disease. He complained of limitation of motion of major joints and some difficulties with activities of daily living (ADL) performances. DISCUSSION: He had been treated with physical and occupational therapies. After the rehabilitative managements, range of motion and ADL performances improved slightly. CONCLUSION: Active and continuous multimodal rehabilitative treatment would be helpful in managing contracture and functional impairment and preventing the progression of the disease.