Characteristics of Telepresence by Multisensory Feedback and Related Neural Mechanism in Patients with Schizophrenia : A Functional MRI Study.

OBJECTIVES: The multimodal telepresence systems have been adopted in a variety of applications, such as telemedicine, space or underwater teleoperation and videoconference. Multimedia, one of the telepresence systems, has been used in various fields including entertainment, education and communication. The degree of subjective telepresence is defined as the probability that a person perceives to be physically in the remote place when he/she experiences a multisensory feedback from the multimedia. The current study aimed to explore the neural mechanism of telepresence related to multisensory feedback in patients with schizophrenia. METHODS: Brain activity was measured using functional magnetic resonance imaging while fifteen healthy controls and fifteen patients with schizophrenia were experiencing filmed referential conversation at various distances (1 m, 5 m and 10 m). Correlations between the image contrast values and the telepresence scores were analyzed. RESULTS: Subjective telepresence was not significantly different between the two groups. Some significant correlations of brain activities with the telepresence scores were found in the left postcentral gyrus, bilateral inferior frontal gyri, right fusiform gyrus, and left superior temporal sulcus. There were no main effects of group and distance. CONCLUSION: These results suggest that patients with schizophrenia experience telepresence as appropriately as healthy people do when exposed to multimedia. Therefore, patients with schizophrenia would have no difficulty in immersing themselves in multimedia which may be used in clinical training therapies.ope

Efficacy and safety of haloperidol versus atypical antipsychotic medications in the treatment of delirium

BACKGROUND: Most previous studies on the efficacy of antipsychotic medication for the treatment of delirium have reported that there is no significant difference between typical and atypical antipsychotic medications. It is known, however, that older age might be a predictor of poor response to antipsychotics in the treatment of delirium. The objective of this study was to compare the efficacy and safety of haloperidol versus three atypical antipsychotic medications (risperidone, olanzapine, and quetiapine) for the treatment of delirium with consideration of patient age. METHODS: This study was a 6-day, prospective, comparative clinical observational study of haloperidol versus atypical antipsychotic medications (risperidone, olanzapine, and quetiapine) in patients with delirium at a tertiary level hospital. The subjects were referred to the consultation-liaison psychiatric service for management of delirium and were screened before enrollment in this study. A total of 80 subjects were assigned to receive either haloperidol (N = 23), risperidone (N = 21), olanzapine (N = 18), or quetiapine (N = 18). The efficacy was evaluated using the Korean version of the Delirium Rating Scale-Revised-98 (DRS-K) and the Korean version of the Mini Mental Status Examination (K-MMSE). The safety was evaluated by the Udvalg Kliniske Undersogelser side effect rating scale. RESULTS: There were no significant differences in mean DRS-K severity or K-MMSE scores among the four groups at baseline. In all groups, the DRS-K severity score decreased and the K-MMSE score increased significantly over the study period. However, there were no significant differences in the improvement of DRS-K or K-MMSE scores among the four groups. Similarly, cognitive and non-cognitive subscale DRS-K scores decreased regardless of the treatment group. The treatment response rate was lower in patients over 75 years old than in patients under 75 years old. Particularly, the response rate to olanzapine was poorer in the older age group. Fifteen subjects experienced a few adverse events, but there were no significant differences in adverse event profiles among the four groups. CONCLUSIONS: Haloperidol, risperidone, olanzapine, and quetiapine were equally efficacious and safe in the treatment of delirium. However, age is a factor that needs to be considered when making a choice of antipsychotic medication for the treatment of delirium.ope

Predicting cytotoxicity of NSAIDs by establishment of strategy to monitor autophagic flux with imaging methods

Drug repositioning is a new pharmaceutical development strategy to identify new indications from existing drugs. It is a beneficial opportunity to reduce developmental time and expense, and decrease the risk of the new compound. In this study, I propose various applicable methods to figure out NSAIDs’ cytotoxicity and I propose the possibility of drug repositioning of DCF (one of the NSAIDs) to anticancer therapy by investigation of its effect on autophagy. To maintain cell hemostasis, cells require biosynthetic and degradative systems. Autophagy is self-degradative process removing folded and aggregated proteins, entire organelles and protein complexes to recycle. Under starved condition and extracellular stimuli, Autophagy is activated by sequestering obsolete materials in autophagosome which subsequently delivered to the lysosome. Degradation of components in lysosome to maintain the pool of building blocks in cells. Thus, autophagy is known to be induced as a cytoprotective system for cell survival. As autophagy is vital for cell homeostasis, autophagy should be tightly regulated. Otherwise, extremely high or low level of autophagy can cause various diseases such as Alzheimer’s disease, Huntington’s disease, hepatitis and liver injury. Non-steroidal anti-inflammatory drugs (NSAIDs) are cyclooxygenase enzyme (COX) inhibitors relieving pain and inflammation. A variety of NSAIDs are easily prescribed and used worldwide. However, it has recently been reported that NSAIDs induce drug-induced liver injury (DILI) resulting in inhibitory effect on mitochondrial respiratory chain. It also increases cellular ROS level leading to hepatotoxicity and hepatocytes apoptosis. For NSAIDs safety, it is required for evaluation of NSAIDs to predict cytotoxicity. In addition, narrowing down the scope of the drug's effects on cells can prevent and avoid their side effects. To assess toxicity in cell culture, basal cell function or specialized cell function is tested. General cell function is examined including observation of cell viability and nuclear fragmentation. On the other hand, I try to evaluate toxicity by monitoring autophagy, one of the specialized cell functions. Because macroautophagy is a dynamic process involved in many proteins and organelles, it is suitable not only for evaluation of overall cytotoxicity, but for observing specific changes of each autophagic step induced by drugs. Therefore, I propose an applicable imaging method to determine and categorize the effect of NSAIDs according to their effect on autophagy, which helps to figure out the drug cytotoxicity and generally outline the mode of action of medicines. In the case of DCF, I suggest the potential anti-cancer effect of DCF for future drug repositioning possibility. ;약물 재배치 (drug repositioning) 은 기존 약물의 새로운 효과를 확인하는 새로운 제약 개발 전략이다. 이는 신약 개발 시간과 비용을 획기적으로 줄이고 새로운 화합물의 사용 위험을 감소시키는 방법이다. 본 연구에서는 NSAIDs의 세포 독성을 알아보기 위한 다양한 방법을 제안하고, 자가소화작용 (autophagy)에 대한 약물의 효과를 조사하여 Diclofenac (NSAIDs의 하나)의 항암제로의 약물 재배치 가능성을 제안하고자 한다. 세포 내 항상성을 유지하기 위해서는 세포는 세포 내 생합성 및 분해 시스템을 필요로한다. 자가소화작용(autophagy)은 세포 내에 뭉쳐져 있는 단백질 (aggregated protein), 늙고 기능을 제대로 하지 못하는 구성요소들과 세포소기관 (organelle)을 분해하여 세포 내 구성요소로 다시 재활용하는 재활용 시스템이다. 자가소화작용(autophagy)은 세포가 외부의 스트레스 (영양소 부족과 아미노산 부족 등)에서 오토파고좀(autophagosome)을 생성하여 세포 내 물질을 리소좀(lysosome)에 전달하여 분해하여 세포 내 구성요소 풀(pool)을 유지하여 세포 스스로 세포보호(cytoprotective) 작용으로 알려져 있다. 자가소화작용(autophagy)는 세포의 항상성에 필수적이기 때문에 엄격히 규제되어야 하며, 그렇지 않고 극도로 높거나 낮은 수준의 자가소화작용(autophagy)는 알츠하이머병, 헌팅턴병, 간염 및 간 손상과 같은 다양한 질병을 유발할 수 있다. NSAIDs (Non-steroidal anti-inflammatory drugs: 비 스테로이드성 항염증제)는 cyclooxygenase enzyme(COX) inhibitor로써, 염증과 고통을 완화시키는 역할을 한다. 최근에 이런 NSAIDs가 drug-induced liver injury (DILI)를 일으키는 부작용이 보고되면서, 이러한 부작용을 예방하기 위하여 NSAIDs의 독성 평가의 필요성이 높아지고 있다. 우리는 세포의 전체적인 항상성을 담당하고, dynamic한 과정의 autophagy를 이용하여 NSAIDs가 세포에 미치는 영향과 독성을 평가해보고자 하였다. Imaging과 다양한 정량방법을 통해 NSAIDs가 세포에 미치는 독성을 관찰함을 시사한다. Diclofenac의 경우, Diclofenac가 자가소화과정(autophagy)에 미치는 영향을 관찰하여, 결과적으로 이 약품이 잠재적인 항암효과를 가지고 있으므로 향후 약물 재배치 가능성이 있음을 제안한다.I. Abstract 1 II. Introduction 3 A. Drug repositioning 3 1. Overview of drug repositioning 3 2. Several successful examples of drug repositioning for anticancer therapy 3 B. The roles of autophagy. 4 1. Overview of autophagy pathway in mammalian cells 4 2. Three different types of autophagy 5 3. Three main steps in autophagy pathway 8 4. Inducers and inhibitors of autophagy 15 5. Various diseases related to autophagy process 16 C. Non-steroidal anti-inflammatory drugs (NSAIDs) and hepatotoxicity 17 1. NSAIDs and Liver damage from NSAIDs 17 D. Objective of this study 19 III. Material and Methods 20 A. Chemicals and antibodies 20 B. Cell culture and Transfection 21 C. Immunofluorescence and confocal microscopy 21 D. Quantitative analysis of images methods 22 E. Cell cycle arrest and Flow cytometry 23 F. Microtubule assay 24 G. Airy scan confocal Image 24 H. Statistical analysis 25 IV. Results 26 A. Quantitative analysis of autophagy inhibition and activation by NSAIDs 26 B. DCF treatment disrupts endomembrane system affecting PI3P formation on the omegasomes and lysosome activity 35 C. DCF induced mitochondrial fragmentation and mitophagy inhibition in HepG2 cells 43 D. DCF disrupts cell division causing mitotic arrest in Hela H2B-GFP cells and Hela cells 51 E. Microtubule network formation was weakened by DCF in Hela cells and HepG2 cells 58 F. Quantitative analysis of Golgi fragmentations induced by NSAIDs can be used as a toxicity prediction method 64 V. Discussion 67 VI. References 70 VII. 국문초록 7

Optimization of sterilization conditions and prediction of heat penetration for the production of retorted Tteokgalbi

This study was conducted to determine the optimum sterilization conditions for the production of the Tteokgalbi product in retort trays by considering microbiological safety, nutritive value, and sensory qualities, and to predict the temperature profile and effects of sterilization of retorted Tteokgalbi during heat treatment through computer simulation. A total of 27 sterilization conditions with various temperatures, times, and processing methods were tested using a 33 factorial design. Temperature history and sterility of the product were monitored using a F0 sensor, and the quality evaluations of factors such as pH, water activity, viable cell counts, niacin contents, color values, sensory characteristics and textural properties were also carried out on retorted Tteokgalbi products manufactured under each sterilization condition. Quality attributes were significantly affected by the sterilization temperature, time, and processing method at different rates. From response surface methodology and contour analysis, the final optimum sterilization condition of Tteokgalbi product that simultaneously satisfied all specifications was determined to be 119.40℃ for 18.55 min using water cascading rotary mode at a fast heat transfer rate. Heat transfer process and the temperature history of retorted Tteokgalbi product during heat treatment were predicted using a finite element model. The cold point, where the rates of temperature increase and decrease were slowest in the retort tray, was not a geometric center but actually at position (x, y, z = 10.600, 9.267, 0.000) in the Tteokgalbi product, which was located at the innermost part of the retort tray. It was shown that lethality, which was closely related to microbial inactivation, as well as the temperature profile of the finite element model predicted by the computer simulation were highly accurate compared to those of the experimental model. In conclusion, the present study suggests that it is possible to improve microbial safety, sensory attributes and nutritional retention using optimized sterilization conditions for the production of retorted Tteokgalbi product as well as to predict the temperature history and effects of sterilization using a developed mathematical model.;본 연구에서는 트레이형 레토르트 제품의 미생물 안전성 및 품질 최적화를 확보하기 위하여 최적 살균조건을 설정해보고, 컴퓨터 프로그램 제작을 통해 열처리 공정 중 제품의 온도 변화 및 그 살균효과를 정확히 예측해보았다. 1차 연구에서는 33요인 실험설계를 바탕으로 살균 온도, 시간, 방법에 따른 여러 처리 조건에서의 살균 실험을 실시한 후, 각각에 대한 F0값을 측정하였을 뿐만 아니라 미생물검사 및 관능검사를 포함한 다양한 품질 평가를 수행하였다. 반응표면분석을 통해 F0값, pH, Niacin 함량, 색도, 관능적 특성 및 조직감 등의 품질 특성들이 살균 온도, 시간, 방법에 따라 각각 다른 비율로 큰 영향을 받는다는 것을 알 수 있었으며, 등고선 분석을 실시한 결과, 레토르트 떡갈비 제품의 최적 살균조건은 119.4℃에서 18.55분간 열전달 속도가 가장 빠른 회전식으로 살균했을 때라는 결론을 얻었다. 2차 연구에서는 유한요소법을 적용시킨 NISA 프로그램을 이용하여 살균공정 동안 제품의 열전달 과정 및 이에 따른 온도 변화를 예측하였다. 살균 시 변화하는 떡갈비 제품의 온도 분포를 가시적 및 수치적으로 확인한 결과, 그 냉점은 기하학적인 중심이 아닌 용기 내 가장 안쪽에 위치한 고기의 (x, y, z = 10.600, 9.267, 0.000) 부분이었다. 제작된 NISA 프로그램을 통해 예측된 냉점의 온도 변화는 실험적 모델과 상당히 높은 상관관계를 나타낼 만큼 정확도가 있었으며, 그 살균 정도 또한 매우 유사하게 예측되었음이 확인되었다. 이와 같은 실험 결과를 바탕으로 하여 영양성분 손실 및 관능적 품질 저하를 최대한 방지하는 동시에 안전성을 충분히 확보한 레토르트 떡갈비 제품을 생산할 수 있을 것이라 판단되며, 더 나아가 개발된 가열살균 프로그램의 최적화를 통해 많은 실험과정을 거치지 않고도 레토르트 제품의 정확한 온도 변화 및 살균효과를 예측할 수 있는 방안에 대한 활용 가능성이 기대되는 바이다.Ⅰ. Introduction 1 Part 1. A study on optimization of sterilization conditions 6 Ⅱ. Materials and Methods 6 A. Sample preparation 6 B. Experimental design 9 C. Sterilization process 11 D. Measurements of pH and water activity 14 E. Instrumental analysis of texture 14 F. Color measurement 15 G. Quantitative analysis of vitamin B3 16 H. Sensory evaluation 17 I. Microbiological analysis 18 J. Statistical analysis 18 Ⅲ. Results and Discussion 19 A. F0 value 30 B. pH value 31 C. Vitamin B3 (niacin) contents 32 D. Water activity 33 E. Sensory characteristics 38 F. Color values 45 G. Texture properties 46 H. Determination of optimum sterilization conditions 54 Part 2. A study on prediction of temperature profile during sterilization 62 Ⅱ-2. Materials and Methods 62 Ⅲ-2. Results and Discussion 67 Ⅳ. Summary and Conclusion 75 References 77 국문초록 8

Comparison of the characteristics of anhedonia between patients with schizophrenia and depressive disorder

의학과/석사[한글] 즐거움을 경험하는 능력의 감소를 뜻하는 무쾌감증(anhedonia)은 정신분열병 및 우울장애에서 흔하고 치료 저�적이며 사회적 기능을 빈곤하게 하는 핵심 개념이다. 본 연구에서는 쾌감 능력(hedonic capacity)에 초점을 두고 쾌감경험을 세분화하여, 제한적 정보의 예고구간과 충분한 정보의 주제구간의 순차적 경험 과정을 통해 무쾌감증의 특성을 알아보았다. 29명의 정신분열병 환자와 20명의 우울장애 환자, 29명의 정상대조군을 연구대상으로 하여 컴퓨터 동영상을 통해 쾌감경험의 예고구간과 주제구간을 직접 경험하도록 하고, 이로 인해 유발된 쾌감의 정도를 시각적 상사척도를 통해 측정하였다. 각 집단과 구간 간 쾌감점수의 차이를 분석하였고, 유의한 교호작용이 있었다. 쾌감자극의 예고구간에서 주제구간으로의 순차적 경험 중, 정상대조군에서는 예고구간의 쾌감이 이후 주제구간에서 충분한 쾌감점수 상승으로 이어지는 데 반해, 정신분열병 환자군에서는 예고구간의 쾌감이 주제구간의 충분한 쾌감 상승으로 이어지지 않았다. 우울장애 환자군은 두 구간 모두에서 유의하게 낮은 쾌감점수를 보였지만, 구간 사이의 쾌감점수 상승 정도는 정상대조군과 비슷한 경향을 보였다. 즉, 정신분열병 환자의 감정의 결손과정은 쾌감경험의 맥락적 상황에서 전개부의 쾌감이 절정부의 쾌감으로 연결되는 긍정반응 증가(augmentation of positive response)의 결함이고, 우울장애 환자의 감정의 결손은, 긍정반응의 증가는 온전하지만 전반적인 쾌감경험능력의 감소로 인해 즐거움에 대한 반응이 저하되는 과정이라 할 수 있겠다. [영문]ope

사회불안장애 환자에서의 왜곡된 주의초점과 관련된 신경매개체

Dept. of Medicine/박사Social anxiety disorder is characterized by heightened anxiety and avoidance of social situations. Emotional and physiological anxiety reaction in social anxiety disorder is known to be triggered by cognitive distortions that automatically appear in social situations. The present study aimed to elucidate the neural basis of attentional bias toward internal and external threats as a core element of social anxiety. In addition, this study aimed to investigate serotonin-1A receptor binding potentials in social anxiety disorder to figure out the association between the distortion of attentional focus and serotonin, which has a pivotal role in the modulation of anxiety and fear reactions. The modified face-in-the-crowd-effect task was performed by 22 patients with social anxiety disorder and 20 comparison subjects while undergoing functional magnetic resonance imaging (fMRI). Participants were instructed to find contempt face among angry or happy faces of the crowd with different levels of internal threat (participants’ own pulse-sound versus control-sound) and external threat (8-crowd versus 4-crowd of faces). Fifteen patients with social anxiety disorder and 15 comparison subjects underwent positron emission tomography (PET) scanning with the 18F-FCWAY. The 2 x 2 (internal x external factor) repeated measures analyses of variance in each group showed that the accuracy of the patient group revealed significant internal x external interaction effect and main effects for these factors. The accuracy of the comparison group was shown significant main effects for the internal and the external factors, but no interaction effect. The fMRI result showed that the patient group revealed main effect of internal threat in the orbitofrontal cortex, insula, and rostral anterior cingulate cortex, main effect of external threat and interaction effect in the posterior cingulate cortex. The comparison group showed main effect of internal threat and interaction effect in the temporo-parietal junction, but no main effect of external threat. The orbitofrontal activity, during the internal and external attention with the modified face-in-the-crowd-effect task, positively correlated with the level of depression and negatively correlated with the level of global functioning in patients. In addition, there were significant associations between the insular activity and the severity of social anxiety, and between the anterior cingulate activity and the level of fear of negative evaluation. The PET result showed greater binding potentials of serotonin-1A receptor in midline structures, such as the orbitofrontal, anterior cingulate, and frontopolar cortices. Behavioral results imply the interactive process of internal and external focus of attention throughout the course of social situationss. The fMRI results of distinctive neural activity on the limbic and paralimbic system during self-focused attention and attentional bias toward external threats suggest the role of the orbitofrontal cortex, insula, and anterior cingulate cortex as compensatory response, anxiety reaction related to self-focused attention, and distorted cognitive control, respectively, in patient with social anxiety disorder. Finally, the PET results of increased binding potentials in these regions support the role of serotonin-1A receptor on the distortion of attentional focus in patients with social anxiety disorder.restrictio

Distinct neural responses used to gain insight into hallucinatory perception in patients with schizophrenia

OBJECTIVE: Most patients with schizophrenia suffer from various types of hallucinations, which commonly produce distress, functional disability or behavioral dyscontrol. The neural process of adapting to hallucinations in patients with schizophrenia remains unknown. METHODS: Functional magnetic resonance imaging (MRI) responses to an unusual threatening visual stimulus designed to simulate a hallucinatory experience were compared between 16 patients with schizophrenia and 17 healthy controls. Linear and quadratic repetition-variant as well as repetition-invariant responses to the stimulus were compared between the two groups. RESULTS: Repetition-invariant responses were similar between patients with schizophrenia and healthy controls. Patients with schizophrenia exhibited a linear activation pattern in the anterior cingulate, whereas healthy controls exhibited a parabolic activation pattern in the anterior prefrontal cortex, occipito-temporal junction and amygdala. CONCLUSIONS: These results provide us with a better understanding of the neural processes involved in gaining insight into unreality. Patients with schizophrenia may use a salience-related region instead of reality monitoring-related regions to react to the unusual stimuli, and this peculiarity of the neural processes may be related to vulnerability to psychosis.ope

Comparison of the Characteristics of Anhedonia between Patients with Schizophrenia and Depressive Disorder

OBJECTIVES: Anhedonia, defined as an inability to experience pleasure, has been considered to be a core feature of schizophrenia and depression. The purpose of the present study was to compare the specific characteristics of anhedonia in patients with the two illnesses by examining hedonic capacity during phased hedonic experience. METHODS: Hedonic rating tasks, using the film clips of physical and social hedonic stimuli and neutral stimuli, were performed by 29 patients with schizophrenia, 20 patients with depression, and 29 normal controls. Each task consisted of 'preview phase' with insufficient emotional information, and a subsequent 'theme phase' with sufficient emotional information. RESULTS: In normal controls, the mean hedonic score was increased in the theme phase compared with the preview phase, suggesting an appropriate augmentation of the hedonic response. In patients with schizophrenia, hedonic scores in the preview phase were comparable with those in normal controls, but showed deficient augmentation in the theme phase. In patients with depressive disorder, the range of increments in scores between the preview and theme phases was normal, but the scores themselves were lower in both phases than in the other two groups. CONCLUSION: The results indicate that patients with schizophrenia show a deficient augmentation of the hedonic response, whereas patients with depressive disorder have a pervasive lack of hedonic capacityope

영어동화를 활용한 초등영어 읽기·쓰기 능력 향상에 관한 연구

학위논문(석사)아주대학교 교육대학원 :초등영어교육,2011. 8Maste

터너증후군 환자에서 Y 염색체 특이 유전자 검색

학위논문(석사)--서울대학교 대학원 :의학과 산부인과학전공,2002.Maste