Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Cyclin-Dependent Kinase 5 ; Cyclin-Dependent Kinases ; Dopaminergic Neurons ; Homeostasis ; Mitochondria ; Mitochondrial Dynamics ; Neurodegenerative Diseases ; Parkinson Disease ; Phosphorylation ; Phosphotransferases ; Primates ; Substantia Nigra

BACKGROUND AND OBJECTIVES: Ergonovine stress echocardiography (ErgECHO) has been proposed as a noninvasive tool for the diagnosis of coronary vasospasm. However, concern over the safety of ErgECHO remains. This study was undertaken to investigate the safety and prognostic value of ErgECHO in a large population. METHODS: We studied 3,094 consecutive patients from a single-center registry who underwent ErgECHO from November 2002 to June 2009. Medical records, echocardiographic data, and laboratory findings obtained from follow-up periods were analyzed. RESULTS: The overall positive rate of ErgECHO was 8.6%. No procedure-related mortality or myocardial infarction (MI) occurred. Nineteen patients (0.6%) had transient symptomatic complications during ErgECHO including one who was successfully resuscitated. Cumulative major adverse cardiac events (MACEs) occurred in 14.0% and 5.1% of the patients with positive and negative ErgECHO results, respectively (p < 0.001) at a median follow-up of 10.5 years. Cox regression survival analyses revealed that male sex, age, presence of diabetes, total cholesterol level of >220 mg/dL, and positive ErgECHO result itself were independent factors associated with MACEs. CONCLUSIONS: ErgECHO can be performed safely by experienced physicians and its positive result may be an independent risk factor for long-term adverse outcomes. It may also be an alternative tool to invasive ergonovine-provoked coronary angiography for the diagnosis of vasospastic angina.
Cholesterol ; Coronary Angiography ; Coronary Vasospasm ; Diagnosis ; Echocardiography ; Echocardiography, Stress ; Ergonovine ; Follow-Up Studies ; Humans ; Male ; Medical Records ; Mortality ; Myocardial Infarction ; Prognosis ; Risk Factors

PURPOSE: The prefrontal lobe, supplementary motor area, cerebellum, and basal ganglia are activated during gait. In addition, gait is controlled by nerves, such as the corticospinal tract (CST) and corticoreticular pathway (CRP). In this study, the presence of an injury to the CST and CRP was identified by diffusion tensor imaging and the characteristics of the gait pattern were investigated according to inferior cerebral artery infarction. METHODS: One patient and six control subjects of a similar age participated. A 69-year-old female patient had an injury to the left basal ganglia, insular gyrus, corona radiata, dorsolateral prefrontal cortex, and postcentral gyrus due to an inferior cerebral artery infarction. Diffusion tensor imaging (DTI) data was acquired 4 weeks after the stroke. The kinematic and spatio-temporal parameters of gait were collected using a three-dimensional gait analysis system. RESULTS: On 4 weeks DTI, the CST and CRP in the affected hemisphere did not show injury to the affected and unaffected hemisphere. Gait analysis showed that the cadence of spatio-temporal parameter was decreased significantly in the patient. The angle of the knee joint was decreased significantly in the affected and unaffected sides compared to the control group. CONCLUSION: The results of diffusion tensor imaging showed that although the patient was evaluated to be capable of an independent gait, the quality and quantity of gait might be reduced. This study could help better understand the gait ability analysis of stroke patients and the abnormal gait pattern of patients with a brain injury.
Aged ; Basal Ganglia ; Brain Injuries ; Cerebellum ; Cerebral Arteries ; Diffusion Tensor Imaging ; Female ; Gait* ; Humans ; Infarction ; Knee Joint ; Motor Cortex ; Prefrontal Cortex ; Pyramidal Tracts* ; Somatosensory Cortex ; Stroke*

Changes over time in pathogens and their antibiotic sensitivity resulting from the recent overuse and misuse of antibiotics in otitis media (OM) have complicated treatment. This study evaluated changes over 5 years in principal pathogens and their antibiotic sensitivity in patients in Korea diagnosed with acute OM (AOM) and OM with effusion (OME). The study population consisted of 683 patients who visited the outpatient department of otorhinolaryngology in 7 tertiary hospitals in Korea between January 2010 and May 2015 and were diagnosed with acute AOM or OME. Aural discharge or middle ear fluid were collected from patients in the operating room or outpatient department and subjected to tests of bacterial identification and antibiotic sensitivity. The overall bacteria detection rate of AOM was 62.3% and OME was 40.9%. The most frequently isolated Gram-positive bacterial species was coagulase negative Staphylococcus aureus (CNS) followed by methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), and Streptococcus pneumonia (SP), whereas the most frequently isolated Gram-negative bacterium was Pseudomonas aeruginosa (PA). Regardless of OM subtype, ≥ 80% of CNS and MRSA strains were resistant to penicillin (PC) and tetracycline (TC); isolated MRSA strains showed low sensitivity to other antibiotics, with 100% resistant to PC, TC, cefoxitin (CFT), and erythromycin (EM); and isolated PA showed low sensitivity to quinolone antibiotics, including ciprofloxacin (CIP) and levofloxacin (LFX), and to aminoglycosides. Bacterial species and antibiotic sensitivity did not change significantly over 5 years. The rate of detection of MRSA was higher in OME than in previous studies. As bacterial predominance and antibiotic sensitivity could change over time, continuous and periodic surveillance is necessary in guiding appropriate antibacterial therapy.

PURPOSE: Gait variability is defined as the intrinsic fluctuations which occur during continuous gait cycles. Increased gait variability is closely associated with increased fall risk in older adults. This study investigated the influence of attention-demanding tasks on gait variability in elderly healthy adults. METHODS: We recruited 15 healthy elderly adults in this study. All participants performed two cognitive tasks: a subtraction dual-task (SDT) and working memory dual-task (WMDT) during gait plus one normal gait. Using the LEGSys+ system, we measured the coefficient of variation (CV %=100×[standard deviation/mean]) for participants' stride time, stride length, and stride velocity. RESULTS: SDT gait showed significant increment of stride time variability compared with usual gait (p < 0.05), however, stride length and velocity variability did not difference between SDT gait and usual gait (p>0.05). WMDT gait showed significant increment of stride time and velocity variability compared with usual gait (p < 0.05). In addition, stride time variability during WMDT gait also significantly increased compared with SDT gait (p < 0.05). CONCLUSION: We reported that SDT and WMDT gait can induce the increment of the gait variability in elderly adults. We assume that attention demanding task based on working memory has the most influence on the interference between cognitive and gait function. Understanding the changes during dual task gait in older ages would be helpful for physical intervention strategies and improved risk assessment.
Adult* ; Aged* ; Aging ; Gait* ; Humans ; Memory, Short-Term ; Risk Assessment

BACKGROUND AND OBJECTIVES: This study was designed to assess the characteristics of patients according to the degree and audiogram shape of hearing loss and the association of these characteristics with hearing aids (HA) choice, return rate, and cause of return. SUBJECTS AND METHODS: This study included 460 individuals who received HAs from 2011 to 2015. The relationships between type of HA and age, primary and accompanying symptoms, HA choice and return and cause of return were evaluated according to the degree and pattern of hearing loss. RESULTS: HA type did not differ significantly according to the degree and pattern of hearing loss. Intensity of hearing loss was greater in male than in female (p<0.05). Open and completely-in-canal types of HA decreased with age (p<0.05). As degree of hearing loss intensified, behind-the-ear and in-the-ear types increased and Open type decreased (p<0.05). The HA return rate was 9.7%, but was not associated with degree or pattern of hearing loss. The main causes of HA return were costs, psychological fears and adaptive failure. CONCLUSIONS: Choice of HA is affected by age, sex, and degree and pattern of hearing loss. HA for hearing rehabilitation in patients with hearing loss can be personalized according to each patient's characteristics and tendencies.
Female ; Hearing Aids* ; Hearing Loss* ; Hearing* ; Humans ; Male ; Rehabilitation

Paroxysmal nocturnal hemoglobinuria (PNH) is a progressive, systemic, life-threatening disease, characterized by chronic uncontrolled complement activation. A retrospective analysis of 301 Korean PNH patients who had not received eculizumab was performed to systematically identify the clinical symptoms and signs predictive of mortality. PNH patients with hemolysis (lactate dehydrogenase [LDH] > or = 1.5 x the upper limit of normal [ULN]) have a 4.8-fold higher mortality rate compared with the age- and sex-matched general population (P < 0.001). In contrast, patients with LDH < 1.5 x ULN have a similar mortality rate as the general population (P = 0.824). Thromboembolism (TE) (odds ratio [OR] 7.11; 95% confidence interval [CI] (3.052-16.562), renal impairment (OR, 2.953; 95% CI, 1.116-7.818) and PNH-cytopenia (OR, 2.547; 95% CI, 1.159-5.597) are independent risk factors for mortality, with mortality rates 14-fold (P < 0.001), 8-fold (P < 0.001), and 6.2-fold (P < 0.001) greater than that of the age- and sex-matched general population, respectively. The combination of hemolysis and 1 or more of the clinical symptoms such as abdominal pain, chest pain, or dyspnea, resulted in a much greater increased mortality rate when compared with patients with just the individual symptom alone or just hemolysis. Early identification of risk factors related to mortality is crucial for the management of PNH. This trial was registered at www.clinicaltrials.gov as NCT01224483.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Area Under Curve ; Child ; Dyspnea/etiology ; Female ; Hemoglobinuria, Paroxysmal/*diagnosis/drug therapy/mortality ; Hemolysis ; Humans ; Kaplan-Meier Estimate ; Kidney Diseases/complications/diagnosis ; L-Lactate Dehydrogenase/metabolism ; Male ; Middle Aged ; Odds Ratio ; ROC Curve ; Registries ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Thromboembolism/complications/diagnosis ; Young Adult

Xanthogranulomatous pyelonephritis (XP) is an uncommon, chronic, destructive, granulomatous disease of the renal parenchyma. The condition is generally associated with long-term urinary tract obstruction and infection, although the precise etiology of disease remains unknown. The condition often mimics neoplastic and inflammatory diseases, and XP associated with actinomycosis is extremely uncommon. A 60 year-old male was admitted complaining of abdominal pain and weight loss. His radiological findings were suggestive of metastatic kidney cancer, and we performed radical laparoscopic nephrectomy and mesenterectomy for diagnostic purposes. Pathologically, actinomycosis combined with XP was evident. We report here a rare case of XP associated with actinomycosis.
Abdominal Pain ; Actinomycosis* ; Humans ; Kidney Neoplasms* ; Kidney* ; Male ; Nephrectomy ; Pyelonephritis ; Pyelonephritis, Xanthogranulomatous* ; Urinary Tract ; Weight Loss

Human mesenchymal stem cells (MSCs) have been used in cell-based therapy to promote revascularization after peripheral or myocardial ischemia. High levels of reactive oxygen species (ROS) are involved in the senescence and apoptosis of MSCs, causing defective neovascularization. Here, we examined the effect of the natural antioxidant lycopene on oxidative stress-induced apoptosis in MSCs. Although H2O2 (200 muM) increased intracellular ROS levels in human MSCs, lycopene (10 muM) pretreatment suppressed H2O2-induced ROS generation and increased survival. H2O2-induced ROS increased the levels of phosphorylated p38 mitogen activated protein kinase (MAPK), Jun-N-terminal kinase (JNK), ataxia telangiectasia mutated (ATM), and p53, which were inhibited by lycopene pretreatment. Furthermore, lycopene pretreatment decreased the expression of cleaved poly (ADP ribose) polymerase-1 (PARP-1) and caspase-3 and increased the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), which were induced by H2O2 treatment. Moreover, lycopene significantly increased manganese superoxide dismutase (MnSOD) expression and decreased cellular ROS levels via the PI3K-Akt pathway. Our findings show that lycopene pretreatment prevents ischemic injury by suppressing apoptosis-associated signal pathway and enhancing anti-oxidant protein, suggesting that lycopene could be developed as a beneficial broad-spectrum agent for the successful MSC transplantation in ischemic diseases.
Aging ; Apoptosis* ; Ataxia Telangiectasia ; bcl-2-Associated X Protein ; Caspase 3 ; Humans* ; Lymphoma, B-Cell ; Mesenchymal Stromal Cells* ; Myocardial Ischemia ; Oxidative Stress ; Phosphotransferases ; Protein Kinases ; Reactive Oxygen Species ; Signal Transduction ; Superoxide Dismutase

PURPOSE: The aim of this study was to estimate the effect of counting numbers out for giving breaths on the interruption time (IT) of chest compressions (CCs) and chest compression fraction (CCF) in the 2-rescuer cardiopulmonary resuscitation (CPR). METHODS: Thirty medical students were enrolled in this randomized control simulation study, and were randomly divided into the control group and the study group. Both groups performed 2-rescuer CPR for 5-cycles with giving breaths using a bag-mask. Only participants in the study group were instructed to count numbers out for each breath verbally ("one, two") at the end point of each inspiration period and immediately perform CCs at the point of counting "two". RESULTS: However, no differences in terms of depth, rate, incorrect location, and duty cycle of CCs, as well as ventilation volume of each breath, time to delivery of two breaths, and counts of breathing during 1 minute were observed between the two groups. CONCLUSION: The study group had significantly shorter IT and higher CCF compared with the control group. And no significant differences in the other measured parameters of CPR quality were observed between the two groups.
Cardiopulmonary Resuscitation* ; Heart Massage ; Humans ; Manikins* ; Pilot Projects* ; Respiration ; Respiration, Artificial ; Students, Medical ; Thorax* ; Ventilation