Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE. The results showed that the genes related to the MAP kinase and calcium-signaling pathways were significantly downregulated in CTE. The altered expression of protein phosphatases (PPs) in these networks further suggested that the tauopathy observed in CTE involves common pathological mechanisms similar to Alzheimer's disease (AD). Using cell lines and animal models, we also showed that reduced PPP3CA/PP2B phosphatase activity is directly associated with increases in phosphorylated (p)-tau proteins. These findings provide important insights into PP-dependent neurodegeneration and may lead to novel therapeutic approaches to reduce the tauopathy associated with CTE.
Alzheimer Disease ; Brain ; Brain Injury, Chronic* ; Cell Line ; Craniocerebral Trauma ; Gene Expression Profiling* ; Humans ; Models, Animal ; Neurodegenerative Diseases ; Phosphoprotein Phosphatases ; Phosphotransferases ; Sequence Analysis, RNA ; Tauopathies* ; Transcriptome*

BACKGROUND AND PURPOSE: To compare the efficacy and safety of antiplatelet agents for the secondary prevention of ischemic stroke based on cytochrome P450 2C19 (CYP2C19) polymorphisms. METHODS: This study was a prospective, multicenter, randomized, parallel-group, open-label, blind genotype trial. First time non-cardiogenic ischemic stroke patients were enrolled and screened within 30 days. Participants were randomized to receive either triflusal or clopidogrel for secondary stroke prevention. The primary outcome was the time from randomization to first recurrent ischemic stroke or hemorrhagic stroke. RESULTS: The required sample size was 1,080 but only 784 (73%) participants were recruited. In patients with a poor CYP2C19 genotype for clopidogrel metabolism (n=484), the risk of recurrent stroke among those who received triflusal treatment was 2.9% per year, which was not significantly different from those who received clopidogrel treatment (2.2% per year; hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.60–2.53). In the clopidogrel treatment group (n=393), 38% had good genotypes and 62% poor genotypes for clopidogrel metabolism. The risk of recurrent stroke in patients with a good CYP2C19 genotype was 1.6% per year, which was not significantly different from those with a poor genotype (2.2% per year; HR, 0.69; 95% CI, 0.26–1.79). CONCLUSIONS: Whilst there were no significant differences between the treatment groups in the rates of stroke recurrence, major vascular events, or coronary revascularization, the efficacy of antiplatelet agents for the secondary prevention of stroke according to CYP2C19 genotype status remains unclear.
Cytochrome P-450 CYP2C19 ; Cytochrome P-450 Enzyme System* ; Cytochromes* ; Genotype ; Humans ; Metabolism ; Platelet Aggregation Inhibitors ; Prospective Studies ; Random Allocation ; Recurrence ; Sample Size ; Secondary Prevention* ; Stroke*

OBJECTIVE: Sacral insufficiency fracture (SIF) contributes to severe low back pain. Prolonged immobilization resulting from SIF can cause significant complications in the elderly. Sacroplasty, a treatment similar to vertebroplasty, has recently been introduced for providing pain relief in SIF. The purpose of this study is to investigate the clinical short-term effects of percutaneous sacroplasty on pain and mobility in SIF. METHODS: This study is conducted prospectively with data collection. Sixteen patients (3 men and 13 women) with a mean age of 77.5 years (58 to 91) underwent sacroplasty. Patients reported visual analogue scale (VAS; 0–10) and Oswestry disability index (ODI; 0–100%) scores. VAS and ODI scores were collected preoperatively and again at one day, one month, and three months postoperatively. Questionnaires measuring six activities of daily living (ADLs) including ambulating, performing housework, dressing, bathing, transferring from chair, and transferring from bed were collected. Ability to perform ADLs were reported preoperatively and again at three months postoperatively. RESULTS: The mean preoperative VAS score (mean±SD) of 7.5±0.8 was significantly reduced to 4.1±1.6, 3.3±1.0, and 3.2±1.2 postoperatively at one day, one month, and three months, respectively (p<0.01). The mean ODI score (%) also significantly improved from 59±14 preoperatively to 15.5±8.2 postoperatively at one month and 14.8±8.8 at three months (p<0.01). All ADL scores significantly improved at three months postoperatively (p<0.01). CONCLUSION: Percutaneous sacroplasty alleviates pain quickly and improves mobility and quality of life in patients treated for SIF.
Activities of Daily Living ; Aged ; Bandages ; Baths ; Data Collection ; Fractures, Stress* ; Housekeeping ; Humans ; Immobilization ; Low Back Pain ; Male ; Prospective Studies ; Quality of Life ; Vertebroplasty

Ultraviolet (UV) irradiation is a relevant environment factor to induce cellular senescence and photoaging. Both autophagy- and silent information regulator T1 (SIRT1)-dependent pathways are critical cellular processes of not only maintaining normal cellular functions, but also protecting cellular senescence in skin exposed to UV irradiation. In the present studies, we investigated whether modulation of autophagy induction using a novel synthetic SIRT1 activator, heptasodium hexacarboxymethyl dipeptide-12 (named as Aquatide), suppresses the UVB irradiation-induced skin aging. Treatment with Aquatide directly activates SIRT1 and stimulates autophagy induction in cultured human dermal fibroblasts. Next, we found that Aquatide-mediated activation of SIRT1 increases autophagy induction via deacetylation of forkhead box class O (FOXO) 1. Finally, UVB irradiation-induced cellular senescence measured by SA-β-gal staining was significantly decreased in cells treated with Aquatide in parallel to occurring SIRT1 activation-dependent autophagy. Together, Aquatide modulates autophagy through SIRT1 activation, contributing to suppression of skin aging caused by UV irradiation.
Autophagy ; Cell Aging* ; Fibroblasts ; Humans ; Skin ; Skin Aging

Reversible lesion in the splenium of the corpus callosum in patients with epilepsy is often associated with some antiepileptic drugs. However, topiramate has never been reported as a possible inducer of the focal lesion. We report a case of reversible splenial lesion of the corpus callosum presumed to be induced by low dose topiramate in a patient with chronic migraine.
Anticonvulsants ; Corpus Callosum* ; Epilepsy ; Humans ; Migraine Disorders*

OBJECTIVES: The aim of this study was to identify the association between scoliosis and psychopathological effects using the Military Personality Inventory (MPI). METHODS: A retrospective cross-sectional study was conducted of 19-yr-old examinees admitted to the Military Manpower Administration in Korea from February 2007-January 2010. The authors compared the profiles of MPI of 3004 scoliosis cases with the profiles of MPI of 11920 normal controls. The scoliosis cases were classified into two groups according to severity, including mild to moderate, and severe. RESULTS: There was a significant difference between the two groups based on the validity scales. The neurosis scales, including anxiety, depression, somatization and personality disorder, were significantly different between the groups. Concerning the anxiety, depression and somatization subscales, the scores of the mild to moderate group and the severe group were higher than those of the control group. Regarding the personality disorder subscale, the mild to moderate group was higher than the control group. For the paranoid subscale, there was a significant difference between the groups and the mild to moderate group had a higher score than the control group. Furthermore, the partial eta square was 0.018, 0.019, and 0.018 for anxiety, depression, and somatization respectively, which suggests that scoliosis was significantly associated with symptoms of anxiety, depression, and somatization. CONCLUSION: Young men with scoliosis tended to have higher scores concerning the MPI than young men without scoliosis. In particular, the scores were higher for anxiety, depression, and somatization symptoms. This result shows that scoliosis may have psychopathological effects on young men.
Anxiety ; Cross-Sectional Studies* ; Depression ; Humans ; Korea* ; Male ; Military Personnel* ; Personality Disorders ; Personality Inventory* ; Retrospective Studies* ; Scoliosis* ; Weights and Measures

PURPOSE: This study was conducted to evaluate the impact of supraclavicular lymph node radiotherapy (SCNRT) on N1 breast cancer patients receiving post-lumpectomy whole-breast irradiation (WBI) and anthracycline plus taxane-based (AT) chemotherapy. MATERIALS AND METHODS: We performed a case-control analysis to compare the outcomes of WBI and WBI plus SCNRT (WBI+SCNRT). Among 1,147 patients with N1 breast cancer who received post-lumpectomy radiotherapy and AT-based chemotherapy in 12 hospitals, 542 were selected after propensity score matching. Patterns of failure, disease-free survival (DFS), distant metastasis-free survival (DMFS), and treatment-related toxicity were compared between groups. RESULTS: A total of 41 patients (7.6%) were found to have recurrence. Supraclavicular lymph node (SCN) failure was detected in three patients, two in WBI and one in WBI+SCNRT. All SCN failures were found simultaneously with distant metastasis. There was no significant difference in patterns of failure or survival between groups. The 5-year DFS and DMFS for patients with WBI and WBI+SCNRT were 94.4% versus 92.6% (p=0.50) and 95.1% versus 94.5% (p=0.99), respectively. The rates of lymphedema and radiation pneumonitis were significantly higher in the WBI+SCNRT than in the WBI. CONCLUSION: We did not find a benefit of SCNRT for N1 breast cancer patients receiving AT-based chemotherapy.
Breast Neoplasms* ; Breast* ; Case-Control Studies* ; Disease-Free Survival ; Drug Therapy* ; Humans ; Lymph Nodes ; Lymphatic Irradiation ; Lymphedema ; Mastectomy, Segmental* ; Neoplasm Metastasis ; Propensity Score ; Radiation Pneumonitis ; Radiotherapy ; Radiotherapy, Adjuvant ; Recurrence

PURPOSE: The purpose of this study was to evaluate the impact of postmastectomy radiotherapy (PMRT) on loco-regional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival (OS) in pT1-2N1 patients treated with taxane-based chemotherapy. MATERIALS AND METHODS: We retrospectively reviewed the medical data of pathological N1 patients who were treated with modified radical mastectomy and adjuvant taxane-based chemotherapy in 12 hospitals between January 2006 and December 2010. RESULTS: We identified 714 consecutive patients. The median follow-up duration was 69 months (range, 1 to 114 months) and the 5-year LRRFS, DFS, and OS rates were 97%, 94%, and 98%, respectively, in patients who received PMRT (PMRT [+]). The corresponding figures were 96%, 90%, and 96%, respectively, in patients who did not receive PMRT (PMRT [–]). PMRT had no significant impact on survival. Upon multivariable analysis, only the histological grade (HG) was statistically significant as a prognostic factor for LRRFS and DFS. In a subgroup analysis of HG 3 patients, PMRT (+) showed better DFS (p=0.081). CONCLUSION: PMRT had no significant impact on LRRFS, DFS, or OS in pT1-2N1 patients treated with taxane-based chemotherapy. PMRT showed a marginal benefit for DFS in HG 3 patients. Randomized studies are needed to confirm the benefit of PMRT in high risk patients, such as those with HG 3.
Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Drug Therapy* ; Follow-Up Studies ; Humans ; Mastectomy, Modified Radical ; Radiotherapy* ; Recurrence ; Retrospective Studies*

Methanol poisoning results in neurological complications including visual disturbances, bilateral putaminal hemorrhagic necrosis, parkinsonism, cerebral edema, coma, or seizures. Almost all reported cases of methanol poisoning are caused by oral ingestion of methanol. However, recently there was an outbreak of methanol poisoning via non-oral exposure that resulted in severe neurological complications to a few workers at industrial sites in Korea. We present 3 patients who had severe neurological complications resulting from non-oral occupational methanol poisoning. Even though initial metabolic acidosis and mental changes were improved with hemodialysis, all of the 3 patients presented optic atrophy and ataxia or parkinsonism as neurological complications resulting from methanol poisoning. In order to manage it adequately, as well as to prevent it, physicians should recognize that methanol poisoning by non-oral exposure can cause neurologic complications.
Acidosis ; Ataxia ; Brain Diseases, Metabolic ; Brain Edema ; Coma ; Eating ; Humans ; Korea ; Methanol* ; Necrosis ; Neurologic Manifestations ; Optic Atrophy ; Parkinsonian Disorders ; Poisoning* ; Renal Dialysis ; Seizures

PURPOSE: The aim of this study was to determine the effectiveness of a community-based muscle and joint self-management program with muscle stretching and muscle strengthening exercises for community-dwelling older adults. METHODS: The study was a pre-and-post design in a single group, which examined the effects after the intervention of muscle and joint self-management program for 6 weeks, on the 42 subjects of the elderly who registered in a Community Senior Center in J city. Data analyses were conducted with paired t-test by using a SAS (version 9.2 for Windows) program. RESULTS: The effectiveness of muscle and joint self-management program on shoulder flexibility and right knee extension (flexibility) were significantly improved (t=2.72, p=.010; t=−2.26, p=.029). Joint symptoms (pain, stiffness), physical functioning, depression, fatigue, and left knee extension were not significantly improved after the muscle and joint self-management program. CONCLUSION: The results showed the possibility of this 6-week exercise program in improving shoulder and knee flexibility for community-dwelling older adults.
Adult* ; Aged ; Depression ; Exercise ; Fatigue ; Humans ; Joints* ; Knee ; Muscle Strength ; Pliability ; Self Care* ; Senior Centers ; Shoulder ; Statistics as Topic