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A single-blind study to investigate the effects of noisy galvanic vestibular stimulation (nGVS) in straight walking and 2 Hz head yaw walking for healthy and bilateral vestibular hypofunction (BVH) participants in light and dark conditions. The optimal stimulation intensity for each participant was determined by calculating standing stability on a force plate while randomly applying six graded nGVS intensities (0–1000 µA). The chest–pelvic (C/P) ratio and lateral deviation of the center of mass (COM) were measured by motion capture during straight and 2 Hz head yaw walking in light and dark conditions. Participants were blinded to nGVS served randomly and imperceivably. Ten BVH patients and 16 healthy participants completed all trials. In the light condition, the COM lateral deviation significantly decreased only in straight walking (p = 0.037) with nGVS for the BVH. In the dark condition, both healthy (p = 0.026) and BVH (p = 0.017) exhibited decreased lateral deviation during nGVS. The C/P ratio decreased significantly in BVH for 2 Hz head yaw walking with nGVS (p = 0.005) in light conditions. This study demonstrated that nGVS effectively reduced walking deviations, especially in visual deprived condition for the BVH. Applying nGVS with different head rotation frequencies and light exposure levels may accelerate the rehabilitation process for patients with BVH.Clinical Trial Registration This clinical trial was prospectively registered at www.clinicaltrials.gov with the Unique identifier: NCT03554941. Date of registration: (13/06/2018).

Objective To determine whether ultrasound (US)-detected synovitis affects the therapeutic efficacy of hyaluronic acid (HA) injection for treating knee OA. Methods Patients with symptomatic knee OA were recruited. All the patients received HA injection two times at 2-week intervals. Clinical assessments were performed using a visual analogue scale (VAS) and the Western Ontario and McMaster Universities OA Index (WOMAC) at baseline and 1 and 6 months after treatment. Imaging evaluation was based on complete knee US examination and the Kellgren–Lawrence grading. Suprapatellar synovial fluid (SF) depth, synovial hypertrophy (SH) and vascularity were measured through US. Results In total, 137 patients who fulfilled the inclusion criteria were included in the analysis. All patients demonstrated improvement in VAS and WOMAC scores at 1 and 6 months after treatment (P Conclusion Ultrasound detected suprapatellar effusion predicts reduced efficacy of HA injection in knee OA

Hyaluronic acid (HA) injection into the osteoarthritis (OA) knee is one of the most popular treatment methods. The study aimed to determine whether HA exhibits antioxidant and antiapoptotic functions in the treatment of OA. Sixty-two outpatient patients with a diagnosis of knee OA were recruited. All patients received (HA) injections twice at a 2-week interval. Synovial fluid through sono-guided aspiration was collected for neutrophils isolation. Oxidative stress, apoptotic markers and related pathways in neutrophils were investigated. Among the oxidative stress markers, 4-hydroxynonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) significantly decreased after HA injection, while superoxide dismutase (SOD) and catalase did not change, which indicated that HA injection had an antioxidant effect that was not through activation of antioxidant enzymes. In addition, we found that HA injection decreased p-AKT levels and decreased p-p53 and p-p38 but not p-GSK-3β. Moreover, we confirmed that HA injection reduced proapoptotic markers through a mitochondria-dependent pathway and proinflammatory events. In vitro investigations also confirmed that HA reduced TNF-α-caused apoptosis in chondrocytes, however, this phenomenon was vanished by AKT inhibitor. Taken together, HA injection into human OA knees resulted antioxidant and antiapoptotic functions, as well as reduced inflammation, through modulation of the AKT pathway.

Background Frailty syndrome in older population generates formidable social cost. The early detection of "prefrail" stage is essential so that interventions could be performed to prevent deterioration. The purpose of this study was to organize appropriate physical performance tests into a computerized early frailty screening platform, called frailty assessment tools (FAT) system, to detect individuals who are in the prefrail stage. Methods Four switches, one distance meter, and one power measure were adopted to build the FAT system that could perform six physical performance tests including single leg standing (SLS), repeated chair rise, timed up and go, self-selected walking speed, functional reach, and grip power. Participants over 65 years old were recruited and classified into three groups according to Fried criteria. The differences in variables between prefrail and robust groups were compared by the χ test, independent samples t test, and Mann-Whitney U test, for nominal variables, normal, and non-normal distributive continuous variables, respectively. The statistically significant level was set at 0.05 (α = 0.05). Results Only SLS did not reach significance to distinguish prefrail from robust. Among 35 participants (73.23 ± 5.70 years old), the FAT score predicted that 90.73 ± 19.95% of pre-frail subjects and 15.01 ± 25.25% of robust subjects were in the prefrail stage. Conclusion The FAT system, which provides results immediately, is an advantageous alternative to traditional manual measurements. The use of the FAT score for predicting the prefrail stage will help to provide early intervention to prevent individuals from progressing into frailty. The FAT system provides a more convenient and comprehensive frailty screening. Using this computerized automatic screening platform, it may be possible to expand the scope of frailty prevention.

Osteoarthritis (OA) is a common degenerative disease; however, its exact pathophysiology and early diagnosis are still a challenge. Growing attention to the exosomes may inspire innovations that would make the current management of OA more effective. The exosomes in synovial fluid are relatively stable, and they can be easily isolated by the relatively noninvasive procedure of liquid biopsy to provide diagnostic and monitoring value. Some miRNAs (miR-504, miR-146a, miR-26a, miR-200c, and miR-210) have been known to be secreted in exosomes of OA patients. On the other hand, intraarticular injection of platelet-rich plasma (PRP) is becoming a popular therapy for OA patients. PRP is also a source of exosomes and their numerous contents. It is evident from the literature that PRP-derived exosomes can induce chondrogenic gene expression in OA chondrocytes. Here, we review the latest findings on the roles of exosomes in OA with the emphasis on PRP-derived exosomes and their potential applications for treating OA.

Aerobic exercise induces oxidative stress and DNA damage, nevertheless, lowers cancer incidence. It remains unclear how genetic stability is maintained under this condition. Here, we examined the dynamic change of the tumor suppressor p16INK4a in cells of skeletal muscle among young men following 60-min of aerobic cycling at 70% maximal oxygen consumption (V̇O2max). Rg1 (5 mg, an immunostimulant ginsenoside) and placebo (PLA) were supplemented 1 h before exercise. Data from serial muscle biopsies shows unchanged p16INK4a+ cells after exercise followed by a considerable increase (+21-fold) in vastus lateralis muscle 3 h later. This increase was due to the accumulation of endothelial progenitor cells (p16INK4a+/CD34+) surrounding myofibers and other infiltrated nucleated cells (p16INK4a+/CD34-) in necrotic myofibers. During the Rg1 trial, acute increases of p16INK4a+ cells in the muscle occurred immediately after exercise (+3-fold) and reversed near baseline 3 h later. Rg1 also lowered IL-10 mRNA relative to PLA 3 h after exercise. Post-exercise increases in VEGF mRNA and CD163+ macrophages were similar for PLA and Rg1 trials. Conclusion: The marked increases in p16INK4a protein expression of endothelial progenitor cells in skeletal muscle implicates a protective mechanism for maintaining genetic stability against aerobic exercise. Rg1 accelerates resolution of the exercise-induced stress response.

Background Patients with rheumatoid arthritis are at higher risk of developing stroke due to augmented systemic inflammation. While regular exercise has been shown to reduce inflammation in human subjects, the purpose of our study is to determine whether increased frequency of rehabilitation is protective against stroke or not. Methods A total of 16,224 rheumatoid arthritis patients with a catastrophic illness certificate were identified in our database from 2000 to 2006, and 663 of them developed stroke before the end of 2013. After statistically matching for age, sex, and the time interval between the diagnosis of rheumatoid arthritis and stroke, 642 patients without stroke were identified as the control group. Analyses with Student’s t test and Chi-square test were done to compare the clinical characteristics of patients with and without stroke, and logistic regression analysis was then performed to evaluate the odds ratio of stroke. Results Higher odds ratio of stroke was revealed in patients with hypertension, diabetes mellitus, and moderate degree of rheumatoid arthritis disease severity. Furthermore, more than 40 rehabilitation sessions per year reduced the risk of developing stroke in patients with moderate disease severity. Conclusions Physical activities brought by more rehabilitation sessions are beneficial and should be encouraged in patients with rheumatoid arthritis, particularly for those with higher disease activity but not taking biologic agents.

Recent findings regarding uses of adipose-derived mesenchymal stem cell (MSC)-lysate on weight loss and improved glucose tolerance in mice on a high-fat diet suggest an encouraging possibility of using MSC lysate for an anti-aging intervention in humans. However, weight loss and lipopenia during late life can be as life-threatening as hyperglycemia during early adulthood. For this 3-year lifelong experiment, a total of 92 rats were randomized into the vehicle-injected group (F=22; M=24) and the MSC lysate injected group (F=22, M=24). We examined longevity, spontaneous locomotor activity, and body composition in rats maintained on a normal diet and received an intermittent treatment of human adipose-derived MSC lysate (3 times a week, 11 times a month given every second month), starting at 12 months of age until natural death. In substantiating previous knowledge regarding the effects of long-term MSC lysate treatments on fat loss and insulin resistance, the present findings also highlighted a shortened average lifespan, a longer inactive time, and a greater bone loss with a relative increase of lean mass in MSC lysate rats with respect to controls. Conclusion: Our data suggest that MSC lysate treatments stimulate disparity in tissue development and produce a cachexia-like effect to decrease longevity.

Objective To investigate whether strength or aerobic training can offer significantly more benefits with regarding the activities of daily living of elderly patients with dementia as well as to determine the effects of exercise on cognition, depression, and biochemical markers. Design Single-blind randomized controlled trial. Setting A nursing home for veterans. Participants A volunteer sample of participants (N=80) whose scores on the Mini-Mental State Examination were between 15 and 26 were included. Because of cardiopulmonary or orthopedic conditions that prohibit exercise training, along with any cognitive problems that may impede answering the contents of our questionnaires, 11 participants were excluded. During the exercise training period, 8 participants voluntarily dropped out of the study. Interventions The participants were randomly assigned to perform either strength or aerobic training for a total of 4 weeks. Main Outcome Measures The main outcome measure was the Barthel Index. Other outcome measures included the Mini-Mental State Examination, Montreal Cognitive Assessment, Geriatric Depression Scale, plasma monocyte chemotactic protein-1 levels, insulin-like growth factor-1 levels, and serum brain-derived neurotrophic factor levels. Results After completion of the program, we discovered a significant improvement in the patients’ Barthel Index, Mini-Mental State Examination, Montreal Cognitive Assessment, and plasma monocyte chemotactic protein-1 levels in the strength-training group. For the patients who had received aerobic training, their serum brain-derived neurotrophic factor also improved significantly. However, the degree of improvement regarding these outcome measures did not achieve significant statistical difference between the 2 groups. Conclusions Through our study, an intensive 4-week exercise program, whether it be strength or aerobic training, is evidenced to bring significant benefits to elderly patients with dementia, while the serum brain-derived neurotrophic factor was additionally improved through aerobic training.

Studies have found that many chemotherapy drugs will produce multiple side effects and complications in cancer patients, especially in the case of the cardiovascular disease. This study was intended to investigate whether the exercise training intervention could improve the body composition and exercise responses of patients with head and neck (H&N) cancer who are receiving chemotherapy. This is a randomized controlled trial. Eighty-four H&N patients were assigned to sedentary group or exercise group. The data were collected pretraining and posttraining, where the body composition, heart rate (HR), blood pressure (BP), rate-pressure product (RPP), and exercise capacity were measured. Our data reported that body weight and body mass index were decreased after 8 weeks of chemotherapy in the sedentary group but not in the exercise group. The decreased visceral fat and the increased skeletal muscle rate had been found in the exercise group after 8 weeks of training. In addition, in the exercise group, the HR, HR recovery, BP, BP recovery, RPP, and minutes walking distance were better than the sedentary group. Results from this study suggested exercise training significantly improved exercise responses and body composition. These findings suggested that exercise can help to promote cardiopulmonary fitness and exercise capacity for H&N cancer patients undergoing chemotherapy.

The peripheral sensory system is critical to regulating motor plasticity and motor recovery. Peripheral electrical stimulation (ES) can generate constant and adequate sensory input to influence the excitability of the motor cortex. The aim of this proof of concept study was to assess whether ES prior to each hand function training session for eight weeks can better improve neuromuscular control and hand function in chronic stroke individuals and change electroencephalography-electromyography (EEG-EMG) coherence, as compared to the control (sham ES). We recruited twelve subjects and randomly assigned them into ES and control groups. Both groups received 20-minute hand function training twice a week, and the ES group received 40-minute ES on the median nerve of the affected side before each training session. The control group received sham ES. EEG, EMG and Fugl-Meyer Assessment (FMA) were collected at four different time points. The corticomuscular coherence (CMC) in the ES group at fourth weeks was significantly higher (p = 0.004) as compared to the control group. The notable increment of FMA at eight weeks and follow-up was found only in the ES group. The eight-week rehabilitation program that implemented peripheral ES sessions prior to function training has a potential to improve neuromuscular control and hand function in chronic stroke individuals.

ObjectivesIt has been proven that statin can protect synovial joints from developing osteoarthritis through its anti-inflammatory effects. However, studies on the effect of statins on spinal degenerative joint diseases are few and limited to in vitro studies. Therefore, we investigated the relationship between the statin dosage and the development of spinal degenerative joint diseases.DesignA retrospective cohort study.SettingPatients registered in Taiwan National Health Insurance Research Database.ParticipantsPatients aged 40–65 years old from 2001 to 2010 were included. Those who received statin treatment before 2001, were diagnosed with spinal degenerative joint diseases or received any spinal surgery before 2004 or had any spinal trauma before 2011 were excluded. A total of 7238 statin users and 164 454 non-users were identified and followed up for the next 7 years to trace the development of spinal degenerative joint disease.Outcome measuresThe incident rate of spinal degenerative joint diseases and HRs among the groups treated with different statin dosages.ResultsA higher dosage of statins was associated with a significantly lower risk of developing spinal degenerative joint disease in patients with hypercholesterolaemia. Compared with the group receiving less than 5400 mg of a statin, the HR of the 11 900–28 000 mg group was 0.83 (95% CI 0.70 to 0.99), and that of the group receiving more than 28 000 mg was 0.81 (95% CI 0.68 to 0.97). Results of subgroup analysis showed a significantly lower risk in men, those aged 50–59 years and those with a monthly income less than US$600.ConclusionsOur study’s findings clearly indicated that a higher dosage of statins can reduce the incidence of spinal degenerative joint disease in patients with hypercholesterolaemia, and it can be beneficial for people with a higher risk of spine degeneration.

Benign paroxysmal positional vertigo (BPPV) is one of the most frequently encountered primary complaints in dizziness clinics. The incidence of BPPV has been proven to increase with age. The relationship between BPPV and another neurodegenerative disease, Parkinson's disease (PD), has not been previously discussed. This study aimed to investigate the relationship of BPPV and PD with oxidative stress. A total of 30,811 subjects participated in our cohort study. The study cohort comprised 5057 BPPV patients and a comparison cohort of 25,754 nonBPPV patients. SIRT1 axis gene expression was investigated in BPPV patient blood samples and a PD cell model of 6-hydroxydopamine (6-OHDA)-treated PC-12 cells to elucidate the potential in vitro and in vivo mechanisms of degeneration in PD and BPPV. Our data suggest that BPPV patients with histories of head injuries show a significantly higher hazard to develop subsequent PD (hazard ratio, 3.942; confidence interval, 1.523-10.205, p = 0.005). We also observed that oxidative status is increased in blood samples from patients with BPPV. Our in vitro study suggests that SIRT1 function is inhibited by oxidative stress, which thereby promotes 6-hydroxydopamine-induced cell death. We conclude that BPPV is independently associated with an increased risk of PD. This finding may be attributed to oxidative stress-mediated inhibition of SIRT1 expression levels.

Low back pain is a common clinical problem that causes disability and impaired quality of life. While the reason behind low back pain was largely considered to be of musculoskeletal origin, the contribution of inflammatory cytokines and oxidative stress could never be overlooked. Exercise has been proven to be an effective approach to treat low back pain. However, the mechanism of the exercise effect on the inflammatory cytokines and oxidative stress is still largely unknown. In this study, we revealed that exercise intervention reduces Toll-like receptor 4 (TLR-4) pathway and enhances Sirtuin 1 (SIRT1) expression in low back pain patients. We also confirmed that exercise up-regulates the expression of peroxisome proliferator-activated receptor-gamma, PPAR-γ coactivator-1 and FoxOs family proteins and also increases the activity of catalase and superoxide dismutase in patients with low back pain. Furthermore, we found that exercise intervention attenuates the oxidative stress, pro-inflammatory cytokine concentrations and p53 expression in patients with low back pain. This study demonstrates that exercise intervention improves low back pain symptoms through regulation of the SIRT1 axis with repression of oxidative stress and TLR-4 inhibition.

Rehabilitation is essential for all poststroke patients to improve self-care ability. However, whether an increased frequency of rehabilitation reduces poststroke adverse events remains undetermined.We recruited 4899 patients with newly diagnosed ischemic stroke between January 1, 2000, and December 31, 2008, from our database and divided them into 3 groups according to their Charlson Comorbidity Index, and they were further categorized into 3 groups of different rehabilitation frequencies during their first year after stroke. Clinical adverse events including recurrent stroke, hip fracture, pneumonia, and all-cause mortality were analyzed by Cox regression analysis to investigate the protective effects of aggressive rehabilitation.We discovered that aggressive rehabilitation in the first year after stroke was significantly associated with a lower incidence of recurrent stroke and all-cause mortality despite the severity of patients' comorbidities. Further Cox regression analysis revealed decreased hazard ratios to develop recurrent stroke and all-cause mortality in patients with more intensive rehabilitation (P for trend.05). However, no significant associations between rehabilitation frequency and pneumonia and hip fracture were identified in our study.Intensive rehabilitation during the first year after stroke should be recommended to prevent detrimental adverse events for stroke survivors.

Sit-to-stand (STS) movements are essential for daily activities. Failure to perform STS movements efficiently and smoothly may lead to falls. In this study, we developed a forceplate to analyze vertical ground reaction force (VGRF), STS duration and generated muscle power to investigate which parameters were fall status predictors. A total of 105 participants were included in this study and were grouped into those (1) aged between 20 and 30 years (Young), (2) aged above 65 years without a history of falling (Non-fallers) and (3) aged above 65 with a history of falling in the past 12 months (Fallers). The results indicated a significantly higher maximal lower limb muscle power (MP) for the Young (9.05 ± 3.66 W/kg), followed by Non-fallers (5.50 ± 2.02W/kg) and Fallers (3.66 ± 1.45 W/kg) as well as higher modified falls efficacy scale (MFES) scores for the Young (Young: 9.88 ± 0.10; Non-fallers: 6.27 ± 1.40; Fallers: 4.83 ± 0.89) and shorter times for the five times sit-to-stand test (FSTST) for the young (Young: 6.09 ± 2.20 s; Non-fallers: 15.65 ± 3.30s; Fallers: 19.82 ± 4.46 s). There was a significant difference between the Young group and the Non-fallers in the maximal vertical ground reaction force (VGRF) (138.79 ± 24.20 N/BW in Young, 117.51 ± 8.57 N/BW in old Non-fallers, p < 0.01), and there was a significant difference between the Non-fallers and the Fallers in the duration of the STS movement (2.74 ± 0.87 s for the Non-fallers, 4.27 ± 2.56 s for the Fallers, p < 0.01). The regression analysis results further indicated that only MP and the STS stabilization phase could differentiate individuals who had past fall events. Therefore, the equipment we developed could potentially be useful in the assessment and monitoring of balance and the risk of falling in older people.

Metformin is a kind of oral hypoglycemic agents commonly prescribed to patients with diabetes mellitus. Although past studies had proven its protective effect on cardiovascular risk and related mortality, the evidence of metformin on stroke prevention was still insufficient and conflicting. Our study randomly selected 14,856 patients with diabetes from the database provided by the Taiwan National Health Research Institute, and 2 cohorts were formulated according to whether metformin was in the prescription record. All cases were followed up for 4 years to track their stroke incidence. As a result, 701 (17.5%) of 3999 diabetic patients had stroke without metformin use, whereas 994 (9.2%) of 10,857 patients had stroke with metformin use. Cox proportional hazard regressions showed that the stroke hazard ratio (HR) of metformin was .383. After adjustment for the patients' age, gender, hypertension, atrial fibrillation, hyperlipidemia, coronary artery disease, and medications including antiplatelets, coumadin, statin, and estrogen use, the HR was still .468. Further stratified analysis revealed that metformin had more protective effect in the patients with higher risk of stroke. Therefore, metformin should be placed in priority when prescribing oral hypoglycemic agents for diabetic patients when considering stroke prevention according to our study.

It is generally thought that topical cooling can interfere with blood perfusion and may have positive effects on recovery from a traumatic challenge. This study examined the influence of topical cooling on muscle damage markers and hemodynamic changes during recovery from eccentric exercise. Eleven male subjects (age 20.2 ± 0.3 years) performed 6 sets of elbow extension at 85% maximum voluntary load and randomly assigned to topical cooling or sham groups during recovery in a randomized crossover fashion. Cold packs were applied to exercised muscle for 15 minutes at 0, 3, 24, 48, and 72 hours after exercise. The exercise significantly elevated circulating creatine kinase-MB isoform (CK-MB) and myoglobin levels. Unexpectedly, greater elevations in circulating CK-MB and myoglobin above the control level were noted in the cooling trial during 48-72 hours of the post-exercise recovery period. Subjective fatigue feeling was greater at 72 hours after topical cooling compared with controls. Removal of the cold pack also led to a protracted rebound in muscle hemoglobin concentration compared with controls. Measures of interleukin (IL)-8, IL-10, IL-1β, and muscle strength during recovery were not influenced by cooling. A peak shift in IL-12p70 was noted during recovery with topical cooling. These data suggest that topical cooling, a commonly used clinical intervention, seems to not improve but rather delay recovery from eccentric exercise-induced muscle damage.

Food restriction and weight loss are known to prevent obesity-related heart diseases. This study investigates whether food restriction elicits anti-apoptotic and pro-survival effects on high-fat diet-induced obese hearts. Histopathological analysis, TUNEL assay, and Western blotting were performed on the excised hearts from three groups of Sprague-Dawley rats which were fed with regular chow diet (CON, 13.5 % fat), a high-fat ad libitum diet (HFa, 45 % fat), or a high-fat food-restricted diet (HFr, 45 % fat, maintaining the same weight as CON) for 12 weeks. Body weight, blood pressure, heart weight, triglycerides, insulin, HOMAIR, interstitial spaces, cardiac fibrosis, and cardiac TUNEL-positive apoptotic cells were increased in HFa relative to CON, whereas these parameters were decreased in HFr relative to HFa. The protein levels of cardiac Fas ligand, Fas receptors, Fas-associated death domain (FADD), activated caspase-8, and activated caspase-3 (Fas receptor-dependent apoptotic pathways), as well as t-Bid/Bid, Bax/Bcl-2, Bad/p-Bad, Cytochrome c, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptotic pathways) in HFr were lower than those in HFa. Moreover, the Bcl-xL and IGF-1-related components of IGF-1, p-PI3 K/PI3 K, p-Akt/Akt in HFr were higher than those in HFa. Our findings suggest that a restricted high-fat diet for maintaining weight control could diminish cardiac Fas receptor-dependent and mitochondria-dependent apoptotic pathways as well as might enhance IGF-1-related pro-survival pathways. In sum, food restriction for maintaining normal weight could elicit anti-apoptotic and pro-survival effects on high-fat diet-induced obese hearts.

Mood disorders and the severity of dizziness often interact with each other. However, the impact of age on anxiety and depression in dizzy patients has rarely been explored. The purpose of this study was to evaluate the correlation between the Dizziness Handicap Inventory (DHI) and the Hospital Anxiety and Depression Scale (HADS) in a group of patients with dizziness. The statistical relationships between age and each scale were studied. This cross-sectional study revealed a high correlation between DHI subgroups and HADS subscales. We found statistical correlation between neither age and HADS subscales nor age and DHI subgroups. In addition, Short-Form 36 Health Survey Questionnaires (SF-36) showed a high correlation with the dizziness handicap severity. The present study revealed that age does not influence mood disorders and the severity of dizziness in dizzy patients.

Heart rate variability (HRV) and parasympathetic power are closely related to the well-being and health status in humans. The main goal of the study was to determine whether these measures can reflect recovery status after weight training. After a 10-day detraining period, 7 weightlifters were challenged with a 2-hour weight training which elicited approximately fourfold increases in circulating muscle creatine kinase level and protracted pain feeling (p < 0.05). Weightlifting performance was then evaluated 3, 24, 48, and 72 hours after training to determine the degree of recovery from fatigue. Heart rate variability, circulating dehydroepiandrostendione sulfate (DHEA-S), and muscle damage markers were measured before each performance test. An electrocardiogram was recorded for 5 minutes continuously at rest in seated positions. After training, weightlifting performance of the subjects decreased below baseline in paralleled with suppressed parasympathetic power (high-frequency [HF] HRV), whereas sympathetic power (normalized low-frequency HRV) was slightly elevated at 3 hours of recovery (p < 0.05). Both weightlifting performances and parasympathetic power returned to baseline values in 24 hours and further increased above baseline during 48-72 hours of recovery in a similar fashion (p < 0.05). Circulating DHEA-S level dropped at 24 hours (p < 0.05) and returned to normal values by 48 hours. Muscle pain increased at 3 hours after training and remained higher than baseline values for the 72-hour recovery period (p < 0.05). Our data suggest that parasympathetic power, indicated by HF HRV, is able to reflect the recovery status of weightlifters after training.

We aimed to evaluate the effectiveness of vestibular rehabilitation (VR) exercise between supervised and home-based programs in young and senior age groups of patients with chronic dizziness. Dizziness Handicap Inventory (DHI), Dynamic gait index (DGI), Tinetti fall risk performance scales and Timed “Up and Go” test (TUG) were administered to patients on their initial and follow-up visits for forty-one patients suffering from chronic dizziness. Twenty-eight patients received three 30-min vestibular training exercise sessions per week. Thirteen patients who could not visit our clinic on regular basis were instructed to do the same set of exercises at home, with the same duration and frequency. All scales were evaluated again on their follow-up visits 2 months later. Patients in both groups showed statistically significant improvement in DHI and Tinetti scales. A higher percentage of patients in the supervised-exercise-program (SP) group showed clinically significant outcome improvements. Age was not a predictive factor for rehabilitation outcome. We concluded that for all ages of chronically dizzy patients, 2 months of VR can reduce handicap, improve balance function and a consequent improvement of life quality. Health care professionals need to be educated about the importance of rehabilitation program for treatment of chronic dizziness.

Retinal stem cells bear potency of proliferation, self-renewal, and differentiation into many retinal cells. Utilizing appropriate sensors one can effectively detect the self-renewal and aging process abilities. Silencing information regulator (SirT1), a member of the sirtuin family, is a NAD-dependent histone deacetylase and an essential mediator for longevity in normal cells by calorie restriction. We firstly investigate the SirT1 mRNA expression in retinal stem cells from rats and 19 human eyes of different ages. Results revealed that SirT1 expression was significantly decreased in in vivo aged eyes, associated with poor self-renewal abilities. Additionally, SirT1 mRNA levels were dose-dependently increased in resveratrol- treated retinal stem cells. The expression of SirT1 on oxidative stress-induced damage was significantly decreased, negatively correlated with the level of intracellular reactive oxygen species production. Treatment with resveratrol could effectively further reduce oxidative stress induced by H(2)O(2) treatment in retinal stem cells. Importantly, the anti-oxidant effects of resveratrol in H(2)O(2)-treated retinal stem cells were significantly abolished by knockdown of SirT1 expression (sh-SirT1). SirT1 expression provides a feasible sensor in assessing self-renewal and aging process in retinal stem cells. Resveratrol can prevent reactive oxygen species-induced damages via increased retinal SirT1 expression.

The major obstacle for the treatment of gastric cancer is recurrence and metastasis; yet, its molecular mechanism is largely unknown. 2-methoxyestradiol (2-ME), a metabolite of the estradiol-17beta, has recently been demonstrated to have multifactorial effects against tumor proliferation and angiogenesis; how these effects are interrelated and act cooperatively is the key question to be elucidated. Akt activation was shown to promote cancer cell invasiveness, and inhibition of Akt phosphorylation by 2-ME was also noted. We herein investigated the significance of PI3K/Akt activation in gastric cancer metastasis and the anti-metastatic effect of 2-ME through attenuation of Akt activity. Immunohistochemistry of PI3K, phosphorylated Akt (p-Akt) and phosphorylated Erk (p-Erk) was performed in tumors from 56 gastric cancer patients, and a significant correlation between PI3K/p-Akt and tumor stage/prognosis was demonstrated (p < 0.05). An in vitro study of 7 gastric cancer cell lines showed a remarkable correlation between PI3K and p-Akt. PI3K/p-Akt overexpression was associated with invasiveness/migration; in contrast, phosphorylation of Erk was not shown to be correlated with invasiveness. In addition, metastatic gastric cancer clones expressed a higher level of PI3K/p-Akt. The anti-metastatic effect of a low dose of 2-ME and inactivation of Akt was demonstrated. 2-ME also exhibited an ability to inhibit gastric cancer cell proliferation and induce G2/M cell cycle arrest at a higher concentration than that required for inhibition of migration. We conclude that the activation of PI3K/Akt pathway is involved in the late-stage progression and metastasis of gastric cancer, and attenuation of p-Akt by 2-ME suppresses metastasis.

To investigate the effects of ultrasound-guided injections of hyaluronic acid (HA) versus steroid for trigger fingers in adults.Prospective, double-blinded, randomized controlled study.Tertiary care center.Subjects with a diagnosis of trigger finger (N=36; 39 affected digits) received treatment and were evaluated.Subjects were randomly assigned to HA and steroid injection groups. Both study medications were injected separately via ultrasound guidance with 1 injection.The classification of trigger grading, pain, functional disability, and patient satisfaction were evaluated before the injection and 3 weeks and 3 months after the injection.At 3 months, 12 patients (66.7%) in the HA group and 17 patients (89.5%) in the steroid group exhibited no triggering of the affected fingers (P=.124). The treatment results at 3 weeks and 3 months showed similar changes in the Quinnell scale (P=.057 and .931, respectively). A statistically significant interaction effect between group and time was found for visual analog scale (VAS) and Michigan Hand Outcome Questionnaire (MHQ) evaluation (P.05). The steroid group had a lower VAS at 3 months after injection (steroid 0.5±1.1 vs HA 2.7±2.4; P.001). The HA group demonstrated continuing significant improvement in MHQ at 3 months (change from 3wk: steroid -2.6±14.1 vs HA 19.1±37.0; P=.023; d=.78).Ultrasound-guided injection of HA demonstrated promising results for the treatment of trigger fingers. The optimal frequency, dosage, and molecular weight of HA injections for trigger fingers deserve further investigation for future clinical applications.

Humans must maintain head and trunk stability while walking. The purpose of this study was to compare the kinematics of healthy controls and patients with vestibular hypofunction (VH) when walking and making head rotations of different frequencies in both light and dark conditions. We recruited eight individuals with VH and nine healthy control subjects to perform four tasks at their preferred gait speed, being normal walk, walking and making yaw head rotations at 1.5Hz and 2Hz, and walking in the dark and making yaw head rotations at 1.5Hz. Linear kinematics as well as head, trunk, and pelvis angular velocities were captured using the Vicon motion analysis system (Vicon Motion Systems, Oxford, UK). We found no difference in walking velocities for any of the four walking conditions across groups. The lateral displacement of the center of mass was increased in VH patients. In the dark, patients had more head instability in pitch (larger amplitudes and velocities) even though they were walking and making active yaw head rotations. Patients also had a smaller relative phase angle (mean 3.50±standard deviation 2.13°) than controls (mean 10.31±standard deviation 2.70°) (p

Huntington’s disease is an autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the huntingtin gene. Heart disease is the second leading cause of death in patients with Huntington’s disease. This study was to evaluate whether cardiac Fas-dependent and mitochondria-dependent apoptotic pathways are activated in transgenic mice with Huntington’s disease. Sixteen Huntington’s disease transgenic mice (HD) and sixteen wild-type (WT) littermates were studied at 10.5 weeks of age. The cardiac characteristics, myocardial architecture, and two major apoptotic pathways in the excised left ventricle from mice were measured by histopathological analysis, Western blotting, and TUNEL assays. The whole heart weight and the left ventricular weight decreased significantly in the HD group, as compared to the WT group. Abnormal myocardial architecture, enlarged interstitial spaces, and more cardiac TUNEL-positive cells were observed in the HD group. The key components of Fas-dependent apoptosis (TNF-alpha, TNFR1, Fas ligand, Fas death receptors, FADD, activated caspase-8, and activated caspase-3) and the key components of mitochondria-dependent apoptosis (Bax, Bax-to-Bcl-2 ratio, cytosolic cytochrome c, activated caspase-9, and activated caspase-3) increased significantly in the hearts of the HD group. Cardiac Fas-dependent and mitochondria-dependent apoptotic pathways were activated in transgenic mice with Huntington’s disease, which might provide one of possible mechanisms to explain why patients with Huntington’s disease will develop heart failure.

Migraine and dizziness are relatively common disorders. Patients with dizziness have a higher incidence of migraines than the general population. The discomfort experienced by these patients is often poorly controlled by medication. However, the pathophysiology of vestibular migraine (VM) remains unclear. We hypothesized that patients with VM would experience remission from symptoms after exercise training and that this effect may be mediated through the suppression of cyclooxygenase-2 (COX-2)-mediated inflammation. Thus, the aim of the present study was to investigate the efficacy and possible anti-inflammatory benefits of exercise in patients with VM. We assessed the level of soluble inflammatory mediators in plasma from VM patients and control subjects. Our analysis of cytokine expression in the patients with VM undergoing exercise treatment revealed a significant reduction in pro-inflammatory cytokines and/or cytotoxic factors, such as tumor necrosis factor-α, interleukins, nitric oxide (NO), inducible NO synthase, and reactive oxygen species. In contrast, we found an increase in the level of anti-inflammatory cytokines after exercise. Moreover, the group undergoing exercise training showed significant symptomatic improvement and demonstrated suppressed antioxidant enzyme activity. To summarize, our data suggest that exercise significantly inhibits COX-2 activity, leading to the suppression of pro-inflammatory cytokines and changes in redox status. These results suggest that there is a molecular link between the central nervous system and the immune system. Furthermore, elucidation of the neurobiological mechanisms underlying VM could potentially lead to the development of novel therapeutic interventions for these patients.

The purpose of the study was to determine the effect of ginseng-based steroid Rg1 on TNF-alpha and IL-10 gene expression in human skeletal muscle against exercise challenge, as well as on its ergogenic outcomes. Randomized double-blind placebo-controlled crossover trials were performed, separated by a 4-week washout. Healthy young men were randomized into two groups and received capsule containing either 5 mg of Rg1 or Placebo one night and one hour before exercise. Muscle biopsies were conducted at baseline, immediately and 3 h after a standardized 60-min cycle ergometer exercise. While treatment differences in glycogen depletion rate of biopsied quadriceps muscle during exercise did not reach statistical significance, Rg1 supplementations enhanced post-exercise glycogen replenishment and increased citrate synthase activity in the skeletal muscle 3 h after exercise, concurrent with improved meal tolerance during recovery (P

One of the fundamental aspects of nitric oxide (NO) is the regulation of the inflammatory processes involved in neuronal apoptosis. Expressions of NO and NO synthase (NOS) are considered to be involved in brain tissue injuries and brain tumors. The purpose of our study was to investigate the roles of NO and inducible-form NOS (iNOS) in the pathogenesis of brain tumors. NO levels in the cerebrospinal fluid (CSF) of 36 brain tumor patients were detected utilizing the NO-chemiluminescence method. Deparaffinized tissue sections were immunostained for the presence of antibodies against iNOS and for apoptosis using the TUNEL stain. The results were compared with 10 control patients (with epilepsy and hydrocephalus). Higher levels of NO and iNOS activities may induce immune responses and neurotoxicities. This preliminary study revealed elevated NO and NOS activities with an increased amount of apoptotic processes in brain tumor tissues, which may indicate the possible roles of NO in the formation of brain tumors.

Dammarane steroids (DS) are a class of chemical compounds present in Panax ginseng. Here, we evaluated the effect of 10 weeks of DS supplementation on inflammatory modulation in the soleus muscle following eccentric exercise (EE)-induced muscle damage (downhill running). Eighty rats were randomized into 4 groups of DS supplementation (saline, 20, 60, 120 mg/kg body weight). Inflammatory markers were measured at rest and again 1 h after EE. At rest, NFκB signaling, TNF-alpha and IL-6 mRNAs, 3-nitrotyrosine, glutathione peroxidase, and GCS (glutamylcysteine synthetase) levels were significantly elevated in the skeletal muscle of DS-treated rats in a dose-dependent manner. Additionally, there were no detectable increases in the number of necrotic muscle fibers or CD68+ M1 macrophages. However, muscle strength, centronucleation, IL-10 mRNA expression, and the number of CD163+ M2 macrophages increased significantly over controls with DS treatment in rat soleus muscle. Under EE-challenged conditions, significant increases in muscle fiber necrosis, CD68+ M1 macrophage distribution, and 3-nitrotyrosine were absent in rats that received low and medium doses (20 and 60 mg/kg) of DS treatment, suggesting that DS possess anti-inflammatory action protecting against a muscle-damaging challenge. However, this protective activity was diminished when a high dose of DS (120 mg/kg) was administered, suggesting that DS possess hormetic properties. In conclusion, our study provides new evidence suggesting that DS is an ergogenic component of ginseng that potentiate inflammation at baseline but that produce anti-inflammatory effects on skeletal muscle following muscle-damaging exercise. Furthermore, high doses should be avoided in formulating ginseng-based products.

BackgroundPeripheral vestibular hypofunction is a major cause of dizziness. When complicated with postural imbalance, this condition can lead to an increased incidence of falls. In traditional clinical practice, gaze stabilization exercise is commonly used to rehabilitate patients. In this study, we established a computer-aided vestibular rehabilitation system by coupling infrared LEDs to an infrared receiver. This system enabled the subjects’ head-turning actions to be quantified, and the training was performed using vestibular exercise combined with computer games and interactive video games that simulate daily life activities.MethodsThree unilateral and one bilateral vestibular hypofunction patients volunteered to participate in this study. The participants received 30 minutes of computer-aided vestibular rehabilitation training 2 days per week for 6 weeks. Pre-training and post-training assessments were completed, and a follow-up assessment was completed 1 month after the end of the training period.ResultsAfter 6 weeks of training, significant improvements in balance and dynamic visual acuity (DVA) were observed in the four participants. Self-reports of dizziness, anxiety and depressed mood all decreased significantly. Significant improvements in self-confidence and physical performance were also observed. The effectiveness of this training was maintained for at least 1 month after the end of the training period.ConclusionReal-time monitoring of training performance can be achieved using this rehabilitation platform. Patients demonstrated a reduction in dizziness symptoms after 6 weeks of training with this short-term interactive game approach. This treatment paradigm also improved the patients’ balance function. This system could provide a convenient, safe and affordable treatment option for clinical practitioners.

The main goal of this study was to investigate the long-term effect of daily 8-hour mild intermittent hypoxia (14-15% O2) on glucose tolerance and muscle morphology of Sprague-Dawley rats. The involvement of AMPK-PGC-1alpha-VEGF signaling pathways in the skeletal muscle was also determined during the first 8 hours of hypoxia. We found that mRNA levels of VEGF and PGC-1alpha were significantly increased above control after 8-h mild hypoxia without a change in AMPK phosphorylation. After 8 weeks of mild intermittent hypoxia treatment, plasma glucose and insulin levels in oral glucose tolerance test (OGTT), epididymal fat mass, and body weight were significantly lower compared to the control group. While soleus muscle weight was not changed, capillary and fiber densities in the hypoxia group were 33% and 35% above the control suggesting reorganization of muscle fibers. In conclusion, our data provide strong evidence that long-term mild intermittent hypoxia decreases the diffusion distance of glucose and insulin across muscle fibers, and decreases adiposity in rats. These changes may account for the improved glucose tolerance observed following the 8-week hypoxia treatment, and provides grounds for investigating the development of a mild non-pharmacological intervention in the treatment of obesity and type 2 diabetes.

Cationic polyurethane, a biodegradable non-viral vector, protects DNA from nuclease degradation and helps to deliver genes efficiently. Oct4, a POU-domain transcription factor, is highly expressed in maintaining pluripotency and cellular reprogramming process in stem cells. SirT1, a NAD-dependent histone deacetylase, is an essential mediator of cellular longevity. Herein we demonstrated that both Oct4 and SirT1 (Oct4/SirT1) expression was decreased in an age-dependent manner in retina with aged-related macular degeneration and retinal pigment epithelium cells (RPEs). To investigate the possible rescuing role of Oct4/SirT1, polyurethane-short branch polyethylenimine (PU-PEI) was used to deliver Oct4/SirT1 into aged RPEs (aRPEs) or light-injured rat retinas. Oct4/SirT1 overexpression increased the expression of several progenitor-related genes and the self-renewal ability of aRPEs. Moreover, Oct4/SirT1 overexpression resulted in the demethylation of the Oct4 promoter and enhanced the expression of antioxidant enzymes, which was accompanied by a decrease in intracellular ROS production and hydrogen peroxide-induced oxidative stress. Importantly, PU-PEI-mediated Oct4/SirT1 gene transfer rescued retinal cell loss and improved electroretinographic responses in light-injured rat retinas. In summary, these data suggest that PU-PEI-mediated delivery of Oct4/SirT1 reprograms aRPEs into a more primitive state and results in cytoprotection by regulating the antioxidative capabilities of these cells.

Declined balance functions have adverse effects on elderly population. Lower limbs muscle power training is currently an emerging concept in rehabilitation on individuals with decreased balance and mobility. In this prospective, controlled study, we used a human-computer interactive video-game-based rehabilitation device (LLPR) for training of lower limb muscle power in the elderly. Forty (aged >65 years) individuals were recruited from the community. Twenty participants in the exercise group received 30-min training, twice a week, using the LLPR system. The LLPR system allows participants to perform fast speed sit-to-stand (STS) movements. Twenty age-matched participants in the control group performed slow speed STS movements, as well as strengthening and balance exercises, with the same frequency and duration. The results were compared after 12 sessions (6 weeks) of training. The mechanical and time parameters during STS movement were measured using the LLPR system. Modified falls efficacy scale (MFES), Tinetti Performance-Oriented Mobility Assessment (POMA), function reach test, five times sit to stand (FTSS) and Timed Up and Go (TUG) were administered to participants as clinical assessments. Results showed that in the exercise group, all the mechanical and time parameters showed significant improvement. In control group, only the maximal vertical ground reaction force (MVGRF) improved significantly. For clinical assessments (balance, mobility, and self-confidence), exercise group showed significantly better scores. The STS movements in video-game-based training mimic real life situations which may help to transfer the training effects into daily activities. The effectiveness of lower limb muscle training is worthy of further investigation.

This study aimed to determine the role of DHEA-S in coping against the exercise training mixing aerobic and resistance components. During 5-day successive exercise training, 16 young male participants (19.2 ± 1.2 years) received either a placebo (flour capsule) or DHEA (100 mg/day) in a double-blinded and placebo-controlled design. Oral DHEA supplementation significantly increased circulating DHEA-S by 2.5-fold, but a protracted drop (~35 %) was observed from Day 3 during training. In the Placebo group, only a minimal DHEA-S reduction (~17 %) was observed. Changes in testosterone followed a similar pattern as DHEA-S. Muscle soreness was elevated significantly on Day 2 for both groups to a similar extent. Lower muscle soreness was observed in the DHEA-supplemented group on Day 3 and Day 6. In the Placebo group, training increased circulating creatine kinase (CK) levels by approximately ninefold, while only a threefold increase was observed in the DHEA-supplemented group. This mix-type exercise training improved glucose tolerance in both groups, while lowering the insulin response to the glucose challenge, but no difference between treatments was observed. Our results suggest that DHEA-S may play a role in protecting skeletal muscle from exercise training-induced muscle damage.

Object Glioblastoma, the most common primary brain tumor, has a poor prognosis, even with aggressive resection and chemoradiotherapy. Recent studies indicate that CD133+ cells play a key role in radioresistance and recurrence of glioblastoma. Cyclooxygenase-2 (COX-2), which converts arachidonic acid to prostaglandins, is over-expressed in a variety of tumors, including CD133+ glioblastomas. The COX-2–derived prostaglandins promote neovascularization during tumor development, and conventional radiotherapy increases the proportion of CD133+ cells rather than eradicating them. The aim of the present study was to investigate the role of celecoxib, a selective COX-2 inhibitor, in enhancing the therapeutic effects of radiation on CD133+ glioblastomas. Methods Cells positive for CD133 were isolated from glioblastoma specimens and characterized by flow cytometry, then treated with celecoxib and/or ionizing radiation (IR). Clonogenic assay, cell irradiation, cell cycle analysis, Western blot, and xenotransplantation were used to assess the effects of celecoxib alone, IR alone, and IR with celecoxib on CD133+ and CD133− glioblastoma cells. Three separate xenotransplantation experiments were carried out using 310 severe combined immunodeficient (SCID) mice: 1) an initial tumorigenicity evaluation in which 3 different quantities of untreated CD133– cells or untreated or pretreated CD133+ cells (5 treatment conditions) from 7 different tumors were injected into the striatum of 2 mice (210 mice total); 2) a tumor growth study (50 mice); and 3) a survival study (50 mice). For these last 2 studies the same 5 categories of cells were used as in the tumorigenicity (untreated CD133– cells, untreated or pretreated CD133+ cells, with pretreatment consisting of celecoxib alone, IR alone, or IR and celecoxib), but only 1 cell source (Case 2) and quantity (5 × 104 cells) were used. Results High levels of COX-2 protein were detected in the CD133+ but not the CD133− glioblastoma cells. The authors further demonstrated that 30 μM celecoxib was able to effectively enhance the IR effect in inhibiting colony formation and increasing IR-mediated apoptosis in celecoxib-treated CD133+ glioblastoma cells. Furthermore, reduction in radioresistance was correlated with the induction of G2/M arrest, which was partially mediated through the increase in the level of phosphorylated-cdc2. In vivo xenotransplant analysis further confirmed that CD133+-associated tumorigenicity was significantly suppressed by celecoxib treatment. Importantly, pretreatment of CD133+ glioblastoma cells with a combination of celecoxib and IR before injection into the striatum of SCID mice resulted in a statistically significant reduction in tumor growth and a statistically significant increase in the mean survival rate of the mice. Conclusions Celecoxib combined with radiation plays a critical role in the suppression of growth of CD133+ glioblastoma stemlike cells. Celecoxib is therefore a radiosensitizing drug for clinical application in glioblastoma.

BPPV is a common cause of vertigo. Several treatment procedures can facilitate recovery. In this study, we aimed to identify the demographic features, resolution and recurrence rates and impacts on daily activities in BPPV patient between young and senior age groups in Taiwan. This retrospective study recruited 218 patients of BPPV. Medical history, canal involvement, treatment required for complete resolution, symptom free period and recurrence rates were evaluated between the two age groups. Up to 80.7% of patients were successfully treated by a single treatment. For patients aged more than 65 years, the recurrence rate was 1.7 times higher than that in the younger age group (p = 0.07). The symptom-free period before recurrence was nearly 2.2 times longer in the senior age group (p = 0.03). Work-related activities were influenced more by BPPV in the younger age group (p = 0.03). We conclude that BPPV is prone to occur and recur in people of senior age. Clinicians should have the knowledge to diagnose different types of BPPV and treat it accordingly to prevent further complications.

Atypical teratoid/rhabdoid tumor (AT/RT) is an extremely malignant neoplasm in the central nervous system (CNS) which occurs in infancy and childhood. Recent studies suggested that CD133 could be considered a marker for brain cancer stem-like cells (CSCs). However, the role of CD133 in AT/RT has never been investigated. Herein we report the isolation of CD133-positive cells (CD133(+)), found to have the potential to differentiate into three germ layer tissues, from tissues of nine AT/RT patients. The migration/invasion/malignancy and radioresistant capabilities of CD133(+) were significantly augmented when compared to CD133(-). The clinical data showed that the amount of CD133(+) in AT/RTs correlated positively with the degree of resistance to radiation therapy. Using cDNA microarray analysis, the genotoxic-response profiles of CD133(+) and CD133(-) irradiated with 10 Gy ionizing radiation (IR) were analyzed 0.5, 2, 6, 12 and 24 h post-IR. We then validated these microarray data and showed increased phosphorylation after IR of p-ATM, p-RAD17, and p-CHX2 as well as increased expression of BCL-2 protein in CD133(+) compared to CD133(-). Furthermore, we found that CD133(+) can effectively resist IR with cisplatin- and/or TRAIL-induced apoptosis. Immunohistochemical analysis confirmed the up-regulated expression of p-ATM and BCL-2 proteins in IR-treated CD133(+) xenotransgrafts in SCID mice but not in IR-treated CD133(-). Importantly, the effect of IR in CD133(+) transplanted mice can be significantly improved by a combination of BCL-2 siRNA with debromohymenialdisine, an inhibitor of checkpoint kinases. In sum, this is the first report indicating that CD133(+) AT/RT cells demonstrate the characteristics of CSCs. The IR-resistant and anti-apoptotic properties in CD133(+) may reflect the clinical refractory malignancy of AT/RTs and thus the activated p-ATM pathway and BCL-2 expression in CD133(+) could be possible targets to improve future treatment of deadly diseases like AT/RT.

Objective: The prevalence of bowel and bladder dysfunction, hyperhidrosis, and poor cardiopulmonary endurance is higher for children with cerebral palsy than for the general population. The purpose of this study was to investigate the autonomic function for patients with cerebral palsy. Design: Thirty patients with cerebral palsy and 30 control subjects were enrolled in this study. Power spectrum analysis of heart rate variability was performed under standardized conditions. Results: In both the supine and head-up positions for test subjects, there was no significant difference for the low frequency component of heart rate variability, high frequency component of heart rate variability, or the low frequency/high frequency ratio between the study and control groups. A significantly greater low frequency component of heart rate variability, smaller high frequency component of heart rate variability, and greater low frequency/high frequency ratio while in the head-up position compared with the supine position was noted for the control group, which implies normal sympathovagal balance. A similar phenomenon was not observed for the study group. Conclusions: The disturbed balance of activity between the sympathetic and parasympathetic nervous system observed in the study might result from the loss of hemispheric influence in patients with cerebral palsy; however, further investigation is clearly necessary.