Till date, researchers have been developing animal models of Alzheimer’s disease (AD) in various species to understand the pathological characterization and molecular mechanistic pathways associated with this condition in humans to identify potential therapeutic treatments. A widely recognized AD model that mimics the pathology of human AD involves the intracerebroventricular (ICV) injection with streptozotocin (STZ).However, ICV injection as an invasive approach has several limitations related to complicated surgical procedures. Therefore, in the present study, we created a customized stereotaxic frame using the XperCT-guided system for injecting STZ in cynomolgus monkeys, aiming to establish an AD model. The anatomical structures surrounding the cisterna magna (CM) were confirmed using CT/MRI fusion images of monkey brain with XperCT, the c-arm cone beam computed tomography. XperCT was used to determine the appropriate direction in which the needle tip should be inserted within the CM region. Cerebrospinal fluid (CSF) was collected to confirm the accurate target site when STZ was injected into the CM.Cynomolgus monkeys were administered STZ dissolved in artificial CSF once every week for 4 weeks via intracisterna magna (ICM) injection using XperCT-guided stereotactic system. The molecular mechanisms underlying the progression of STZ-induced AD pathology were analyzed two weeks after the final injection. The monkeys subjected to XperCT-based STZ injection via the ICM route showed features of AD pathology, including markedly enhanced neuronal loss, synaptic impairment, and tau phosphorylation in the hippocampus. These findings suggest a new approach for the construction of neurodegenerative disease models and development of therapeutic strategies.

Ischemic stroke results from arterial occlusion and can cause irreversible brain injury. A non-human primate (NHP) model of ischemic stroke was previously developed to investigate its pathophysiology and for efficacy testing of therapeutic candidates; however, fine motor impairment remains to be well-characterized. We evaluated hand motor function in a cynomolgus monkey model of ischemic stroke. Endovascular transient middle cerebral artery occlusion (MCAO) with an angiographic microcatheter induced cerebral infarction. In vivo magnetic resonance imaging mapped and measured the ischemia-induced infarct lesion. In vivo diffusion tensor imaging (DTI) of the stroke lesion to assess the neuroplastic changes and fiber tractography demonstrated three-dimensional patterns in the corticospinal tract 12 weeks after MCAO. The hand dexterity task (HDT) was used to evaluate fine motor movement of upper extremity digits. The HDT was modified for a home cage-based training system, instead of conventional chair restraint training. The lesion was localized in the middle cerebral artery territory, including the sensorimotor cortex. Maximum infarct volume was exhibited over the first week after MCAO, which progressively inhibited ischemic core expansion, manifested by enhanced functional recovery of the affected hand over 12 weeks after MCAO. The total performance time decreased with increasing success rate for both hands on the HDT. Compensatory strategies and retrieval failure improved in the chronic phase after stroke. Our findings demonstrate the recovery of fine motor skill after stroke, and outline the behavioral characteristics and features of functional disorder of NHP stroke model, providing a basis for assessing hand motor function after stroke.

ymptoms of Parkinson’s disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed the alteration in Parkinsonian tremor signs and the functionality of presynaptic dopaminergic neuron using positron emission tomography imaging of dopamine transporters in these models. In addition, a significant inverse correlation between HDT and DAT level was identified, but no local bias was found. The correlation with intention tremor signs was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.

Fungal balls consist of rounded conglomerates of fungal mycelia, which can form within a preexisting cavity. They are mostly found in the paranasal sinuses in the head and neck regions. Cholesterol granuloma is a fibrotic lesion that develops as a tissue response to a foreign body such as cholesterol crystals or hemosiderin and is often associated with chronic otitis media. We present the unusual case of a 62-year-old male who was treated for chronic otitis media, which was histologically confirmed as a fungal ball and cholesterol granuloma in the middle ear cavity following tympanomastoidectomy. This is the first reported case of synchronous fungal ball and cholesterol granuloma in the middle ear cavity.

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

The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found colocalized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206⁺ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68⁺ microglia/macrophages can therefore be used as a potential therapeutic target.
Brain ; Haplorhini ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; Inflammation ; Macaca mulatta ; Magnetic Resonance Imaging ; Microglia ; Middle Cerebral Artery ; Primates ; Stroke ; Transforming Growth Factor beta

The aim of this project was to use 3D scanning data collected at incident scenes and various evidence to 1) develop surveying methods based on 3D data consisting of overall and detailed scene evidence, captured by long-range and micros-canner, which can be shared by personnel working in different fields such as forensic medicine, video analysis, physical analysis, traffic engineering, and fire investigation; 2) create digital storage for human skeletons and set the foundation for virtual anthropology; and 3) improve the credibility of 3D evidence by virtual remodeling and simulation of incident scenes and evidence to provide a basis for advanced and high-tech scientific investigation. Two complete skeletons of male and female were scanned using 3D micro-scanner. Each bone was successfully reproduced and assembled in virtual space. In addition, recreating evidence scheduled for invasive examination by creating RP (rapid prototype) was possible. These outcomes could play an important role in setting up the new field of virtual anthropology. Case-specific surveying methods were developed through analysis of 3D scanning data collected by long-range surface scanners at the scenes of vehicular accidents, falls, shootings, and violent crimes. A technique and recording method was also developed for detecting forged seals by micro-scanning the pressure exerted on the seal. Appraisal methods developed in this project could be utilized to secure 3D data of human skeletal remains and incident scenes, create a standard for application, and increase objectivity, reproducibility, and accuracy of scanning methods. We plan to develop case-specific 3D data analysis techniques to improve the credibility of analysis at the NFS and to establish a 3D data collection and analysis team.
Crime ; Data Collection ; Female ; Fires ; Forensic Medicine ; Forensic Sciences ; Humans ; Male ; Skeleton ; Statistics as Topic

BACKGROUND AND OBJECTIVES: We performed a retrospective study to elucidate the frequency of tachycardia mechanisms and the characteristics of accessory pathways (APs), confirmed by radiofrequency catheter ablation (RFCA) in pediatric tachycardia. In addition, we analyzed the efficacy and safety of pediatric RFCA. SUBJECTS AND METHODS: The authors retrospectively reviewed the records of a total of 260 patients (aged 2 to 18 years) who had undergone RFCA between August 1993 and July 2011 at two medical centers in Daegu. RESULTS: Two hundred and sixty patients underwent 272 RFCAs at less than 18 years of age. Of these 260 patients, 9 patients (3%) were younger than 6 years, and 175 patients (67%) were older than 12 years. The tachycardia mechanisms observed were atrioventricular reentry tachycardia (AVRT) in 175 patients (65%), atrioventricular nodal reentry tachycardia (AVNRT) in 83 patients (30%), ventricular tachycardia in 12 patients (4%), and atrial tachycardia in 2 patients (0.7%). Among the patients with AVRT, there were 94 concealed APs and 81 manifest APs. Left-side APs were more common in concealed APs than in manifest APs (72/94, 77% vs. 33/81, 41%, p<0.001). Sixty-six percent (55/83) of AVNRT cases were located at the M1 and/or M2 sites. Four patients had multiple tachycardia mechanisms (AVNRT+AVRT) and 9 patients had multiple APs. The recurrence rate was 5% (13/272). Of these recurrent cases, 12 patients had AVRT. The overall success rate was 95%. CONCLUSION: Pediatric RFCA provides a good success rate and an acceptable recurrence. In addition, we suggest that the APs location may be associated with concealed or manifest property of APs.
Catheter Ablation ; Catheters ; Humans ; Pediatrics ; Recurrence ; Retrospective Studies ; Tachycardia ; Tachycardia, Atrioventricular Nodal Reentry ; Tachycardia, Supraventricular ; Tachycardia, Ventricular

PURPOSE: The 2005 guidelines for cardiopulmonary resuscitation (CPR) caution that effective compression is essential (Class I) and chest compression (CC) by rescuers should be switched every 2 minutes to avoid rescuer's fatigue. It is controversial how long effective CC by a single individual can be provided. There are few reports about CPR quality, especially when rescuers perform CC for more than 10 minutes. The mean CPR period was about 30 minutes in Korea. We investigated the quality of CC and rescuer's fatigue after about 30 minutes. METHODS: From April 2009 to July 2009, health care providers (HCPs) were recruited into this study. The study simulated 2 person, in-hospital CPR. On the test day, which had been randomly assigned, each participant performed 7 CCs for about 30 minutes. The period of each CC was 2 minutes, and the period of each circulation check was 5 seconds. Participants' heart rates (HR) and visual analogue scale (VAS) scores for fatigue were obtained before and after each CC. Data for each 2 minutes CC was obtained with the use of Resusci Anne(R) with the Laerdal(R) PC skill reporting system. We used one-way repeated measures ANOVA for comparison of quality and fatigue of each CC and multiple linear regression for finding the predictors for correct CC. SPSS 17.0 was used for analysis. RESULTS: Among a total of 30 HCPs, data from 27 were analyzed. All participants were certified as a BLS provider and some were certified as BLS instructors. The rate of effective compression was 83.8+/-24.3%. Despite 2 min CC tasks were repeated alternatively for about 30 minutes, there were no differences in the number of correct CCs, depth and velocity of compression, and the number of incorrect CCs. CONCLUSION: During in-hospital CPR, HCPs may provide effective chest compressions on shifts with minimal effect of fatigue, even if they provide CC for 30 minutes.
Cardiopulmonary Resuscitation ; Fatigue ; Health Personnel ; Heart Rate ; Humans ; Korea ; Linear Models ; Manikins ; Thorax

IgA nephropathy is the most common form of glomerulonephritis characterized by deposit of IgA on mesangium. We experienced an elderly patient who was admitted for generalized edema, and diagnosed IgA nephropathy and early gastric cancer concomittantly. It has been reported that the incidence of nephrotic syndrome combined with malignancy increases with aging. Moreover, close relationship between IgA nephropathy and malignancy has been reported especially in the elderly patient. So, active investigations for possible malignancy are required in case of elderly patient with IgA nephropathy. In this case, we found improved proteinuria and hematuria of the patient after tumor resection during following up. This case suggest causal association between early gastric cancer and IgA nephropathy clinically.
Aged* ; Aging ; Delirium ; Depression ; Edema ; Glomerulonephritis ; Glomerulonephritis, IGA* ; Hematuria ; Humans ; Immunoglobulin A* ; Incidence ; Nephrotic Syndrome ; Proteinuria ; Stomach Neoplasms*