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Clinical and preclinical tolerance protocols for vascularized composite allograft transplantation

  • Yang, Jerry Huanda;Johnson, Ariel C.;Colakoglu, Salih;Huang, Christene A.;Mathes, David Woodbridge
    • Archives of Plastic Surgery
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    • v.48 no.6
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    • pp.703-713
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    • 2021
  • The field of vascularized composite allografts (VCAs) has undergone significant advancement in recent decades, and VCAs are increasingly common and accepted in the clinical setting, bringing hope of functional recovery to patients with debilitating injuries. A major obstacle facing the widespread application of VCAs is the side effect profile associated with the current immunosuppressive regimen, which can cause a wide array of complications such as infection, malignancy, and even death. Significant concerns remain regarding whether the treatment outweighs the risk. The potential solution to this dilemma would be achieving VCA tolerance, which would allow recipients to receive allografts without significant immunosuppression and its sequelae. Promising tolerance protocols are being studied in kidney transplantation; four major trials have attempted to withdraw immunosuppressive treatment with various successes. The common theme in all four trials is the use of radiation treatment and donor cell transplantation. The knowledge gained from these trials can provide valuable insight into the development of a VCA tolerance protocol. Despite similarities, VCAs present additional barriers compared to kidney allografts regarding tolerance induction. VCA donors are likely to be deceased, which limits the time for significant pre-conditioning. VCA donors are also more likely to be human leukocyte antigen-mismatched, which means that tolerance must be induced across major immunological barriers. This review also explores adjunct therapies studied in large animal models that could be the missing element in establishing a safe and stable tolerance induction method.

Efficient Generation of Dopaminergic Neurons from Mouse Ventral Midbrain Astrocytes

  • Jin Yi Han;Eun-Hye Lee;Sang-Mi Kim;Chang-Hwan Park
    • Biomolecules & Therapeutics
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    • v.31 no.3
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    • pp.264-275
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    • 2023
  • Parkinson's disease (PD) is a common neurodegenerative disorder characterized by tremors, bradykinesia, and rigidity. PD is caused by loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN) and therefore, replenishment of DA neurons via stem cell-based therapy is a potential treatment option. Astrocytes are the most abundant non-neuronal cells in the central nervous system and are promising candidates for reprogramming into neuronal cells because they share a common origin with neurons. The ability of neural progenitor cells (NPCs) to proliferate and differentiate may overcome the limitations of the reduced viability and function of transplanted cells after cell replacement therapy. Achaete-scute complex homolog-like 1 (Ascl1) is a well-known neuronal-specific factor that induces various cell types such as human and mouse astrocytes and fibroblasts to differentiate into neurons. Nurr1 is involved in the differentiation and maintenance of DA neurons, and decreased Nurr1 expression is known to be a major risk factor for PD. Previous studies have shown that direct conversion of astrocytes into DA neurons and NPCs can be induced by overexpression of Ascl1 and Nurr1 and additional transcription factors genes such as superoxide dismutase 1 and SRY-box 2. Here, we demonstrate that astrocytes isolated from the ventral midbrain, the origin of SN DA neurons, can be effectively converted into DA neurons and NPCs with enhanced viability. In addition, when these NPCs are inducted to differentiate, they exhibit key characteristics of DA neurons. Thus, direct conversion of midbrain astrocytes is a possible cell therapy strategy to treat neurodegenerative diseases.

Survey and Suggestions on the Educational and Research Environment of Graduate Students of Korean Medicine: Focusing on fostering of KMD-scientist (한의사과학자 양성을 위한 한의학과 대학원 재학생의 교육 및 연구환경 실태조사와 제언)

  • Myungsun Kim;Myung-Ho Kim;Minjung Lee;Dongyeop Jang;Sa-Yoon Park
    • The Journal of Korean Medicine
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    • v.44 no.3
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    • pp.59-73
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    • 2023
  • Objectives: The role of physician-scientists who bridge the gap between basic science and clinical medicine is crucial in advancing medical innovation. This study aims to examine the educational and research environment and career satisfaction of graduate students in Korean Medicine among those who are Korean medicine doctor (KMD). Methods: This study analyzed the results of a survey consisting of respondents' composition, job status, graduate education and job satisfaction, economic conditions, career determinants, and obstacles to the career path of KMD-scientists from 65 participants including both full-time and part-time graduate students. Results: The results revealed significant differences between full-time and part-time graduate students in terms of weekly hours spent and job priorities, motivation for entering graduate school, career preferences, and desired career paths. The study highlights the need for tailored support for full-time and part-time graduate students and the importance of economic assistance in fostering KM scientists. Economic difficulties were identified as a major obstacle for full-time graduate students pursuing research careers. Tuition fees were found to be a significant burden for all graduate students. Furthermore, it emphasizes the importance of enhancing the research capabilities of part-time graduate students and improving the quality of education to foster KMD-scientists. Conclusion: This research provides essential insights for Korean Medicine colleges and graduate schools to develop targeted improvement plans and effectively train KMD-scientist.

Relationship between plasma flows and the near-Earth tail dipolarizations

  • Lee, Dae-Young;Kim, H.S.;Ohtani, S.
    • Bulletin of the Korean Space Science Society
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    • 2011.04a
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    • pp.29.1-29.1
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    • 2011
  • The magnetic dipolarizations at the tail are often, if not always, associated with plasma flows of some magnitude. The associated flow direction is known to be earthward most often but not necessarily always. It is the primary goal of this paper to clarify the association between dipolarizations and the associated flow characteristics in general, but with a primary emphasis on tailward flow cases. Based on a number of dipolarizations that we identify at the near-Earth tail using the THEMIS tail observations we first confirm that dipolarizations can in general initiate in association with both earthward and tailward flows. Also, the main direction of the plasma flow, whether being earthward or tailward, is not critical in determining the intensity of the dipolarizations. We actually identify some events of tailward flow-associated dipolarizations that are as much intense as the earthward flow-associated events. The occurrence rate of the tailward flow-associated dipolarizations is mainly concentrated in the radial region of < 10 RE and in the local time region of 22-01 hr. However, its relative occurrence rate is rather low, ~19 % in the radial region and ~15.3 % in the local time region, as compared to that for the events associated with all other types of flows. Furthermore, the flow direction often changes no matter whether it is initially earthward or tailward near the onset time. As a consequence, the net transport of the magnetic flux during the main duration of the dipolarization process is earthward for nearly all of the dipolarizations that initiate with dominantly tailward flows near the onset, as is the case for those that initiate with dominantly earthward flows.

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Non-Contact Ultrasonic Testing of Aircraft Joints using Laser Generated Lamb Wave (레이저 여기 램파를 이용한 항공기 판재 접합부의 비접촉식 초음파 검사)

  • Jhang, Kyoung-Young;Kim, Hong-Joon;Ceringlia, Donatella;Djordjevic, Boro
    • Journal of the Korean Society for Nondestructive Testing
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    • v.21 no.2
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    • pp.163-168
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    • 2001
  • Due to aging, adhesively bonded and riveted aircraft lap joints can contain distends, cracks around rivet holes, fatigue induced flaws, and corrosion. It is required for the safety of aircraft to inspect these defects through the whole region of mint in rapid speed. Bond quality or adhesively bonded and riveted aluminum lap splice joints is investigated using non-contact remote ultrasonic nondestructive evaluation (NDE). Non-contact ultrasonic tests are performed using laser generation and air-coupled transducer detection. A Q-switched Nd:YAG laser and a periodic transmission mask are used to generate a selected Lamb mode. The Lamb wave is generated on one side of the lap splice joint, propagates along the plate, interacts with the joint and is detected on the other side by a micromachined air-coupled capacitance transducer. Analysis of recorded signals allows to evaluate the condition of the bond.

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Physical and Psychological Health Status of North Korean Defector Children (북한 이탈 아동의 신체 및 심리적 건강상태 평가)

  • Lee, In-Sook;Park, Ho-Ran;Kim, Yun-Soo;Park, Hyun-Jeong
    • Child Health Nursing Research
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    • v.17 no.4
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    • pp.256-263
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    • 2011
  • The purpose of the study was to evaluate the physical and psychological health status of North Korean defector children and identify associated factors. The participants in the study were 103 children ranging in age from 7 to 14 years old. Physical health status was evaluated through height and weight measurements as well as clinical laboratory results. Psychological health status was assessed using structured survey interviews. Data were analyzed utilizing Pearson correlation coefficients, t-test, ANOVA, and descriptive statistics. On arrival in South Korea, 19% of the children did not meet the child growth standards of South Koreans for height and 15% for weight. However, twelve weeks after, these percentages had decreased significantly. It found that 38.5% of children presented mild posttraumatic reaction and 40.4% presented moderate reaction. Scores for externalizing and internalizing behavior problems were $0.38{\pm}0.30$ and $0.59{\pm}0.36$ respectively. Posttraumatic reaction was higher in girls (t=0.41, p=.03), and boys showed higher externalizing problems (t=2.04, p=.04). Externalizing problems were correlated with gender and internalizing problems were associated with posttraumatic reactions and externalizing problems. The findings indicate that North Korean defector children need timely developmental assessments and tailored intervention programs to meet child growth standards need to be developed.

Expression of Human Cytomegalovirus Immediate Early US3 Gene in Human Fibroblast Cells

  • Lee, Gyu-Cheol;Lee, Chong-Kyo;Ahn, Jin-Hyun;Lee, Chan-Hee
    • Journal of Microbiology
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    • v.38 no.1
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    • pp.24-30
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    • 2000
  • US3 gene is a member of the human cytomegalovirus (HCMV) immediate early gene. Although the precise functions of the US3 gene in HCMV replication and pathogenesis are not known, it has been reported to play a role in inhibiting major histocompatibility class I antigen presentation. For further knowledge of US3 gene expression, rabbit polyclonal antiserum of the US3 gene product was used for indirect immunofluorescence assay. In permissive human foreskin fibroblast (HFF) cells, US3 gene expression was detectable as crescent or half-moon shape in the perinuclear region at immediate early times after virus infection. HFF cells infected with mutant HCMV lacking US3 open reading frames were negative for US3 immunofluorescence assay. Double immunofluorescence assay using monoclonal antibody to gamma adaptin (specific for the Golgi complex) and rabbit anti-US3 antiserum revealed that US3 gene product could be localized to the Golgi complex. At later time after HCMV infection, US3 gene products were detected as globular aggregates in the cytosol. These aggregates were positive for gamma adaptin and stained with preimmune serum, suggesting a nonspecific reaction to the Golgi complex. Northern blot analysis revealed that transcription of US3 was observed only during immediate early times after virus infection (until 6 h postinfection). Therefore US3 gene expression appears to be confined to immediate early time and its gene products are localized to the Golgi complex as crescent shaped forms in the perinuclear cytoplasm.

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Factors affecting hand hygiene behavior among health care workers of intensive care units in teaching hospitals in Korea: importance of cultural and situational barriers

  • Jeong, Heon-jae;Jo, Heui-sug;Lee, Hye-jean;Kim, Min-ji;Yoon, Hye-yeon
    • Quality Improvement in Health Care
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    • v.21 no.1
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    • pp.36-49
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    • 2015
  • In Intensive Care Units (ICUs), where severely ill patients are treated, importance of reducing Hospital Acquired Infection (HAI) cannot be overstated. One of the simplest and most effective actions against HAI is proper hand hygiene (HH) behavior of Health Care Workers (HCWs). However, compliance varies across different cultures and different job types of HCWs (physicians, residents and nurses). This study aims to understand determinants of HH behavior by HCWs' job types in Korea. Qualitative analysis was performed based on Reasoned Action Approach style interviews with staff physicians, residents and nurses across 7 teaching hospitals. We found that all HCWs strongly believe HH is important in reducing HAI. There were, however, job type-specific HH behavior modifying factors; staff physicians stated feeling pressure to be HH behavior role model. Residents identified Quality Improvement team that measured compliance as a facilitator; a notable barrier for residents was senior physicians not washing their hands, because they were afraid of appearing impudent to their seniors. Nurses designated their chief nurse as a key referent. All participants mentioned heavy workload and lack of access to alcohol-based sanitizer as situational barriers, and sore and dry hand as deterrents to HH compliance.

A Training Intervention for Supervisors to Support a Work-Life Policy Implementation

  • Laharnar, Naima;Glass, Nancy;Perrin, Nancy;Hanson, Ginger;Anger, W. Kent
    • Safety and Health at Work
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    • v.4 no.3
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    • pp.166-176
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    • 2013
  • Background: Effective policy implementation is essential for a healthy workplace. The Ryan-Kossek 2008 model for work-life policy adoption suggests that supervisors as gatekeepers between employer and employee need to know how to support and communicate benefit regulations. This article describes a workplace intervention on a national employee benefit, Family and Medical Leave Act (FMLA), and evaluates the effectiveness of the intervention on supervisor knowledge, awareness, and experience with FMLA. Methods: The intervention consisted of computer-based training (CBT) and a survey measuring awareness and experience with FMLA. The training was administered to 793 county government supervisors in the state of Oregon, USA. Results: More than 35% of supervisors reported no previous training on FMLA and the training pre-test revealed a lack of knowledge regarding benefit coverage and employer responsibilities. The CBT achieved: (1) a significant learning effect and large effect size of d = 2.0, (2) a positive reaction to the training and its design, and (3) evidence of increased knowledge and awareness regarding FMLA. Conclusion: CBT is an effective strategy to increase supervisors' knowledge and awareness to support policy implementation. The lack of supervisor training and knowledge of an important but complex employee benefit exposes a serious impediment to effective policy implementation and may lead to negative outcomes for the organization and the employee, supporting the Ryan-Kossek model. The results further demonstrate that long-time employees need supplementary training on complex workplace policies such as FMLA.

Acculturative Stress and Current Perception of Stress in Korean Immigrants (미국이민 한국인의 문화변용 스트레스와 일상생활 스트레스정도에 관한 연구)

  • Shin, Hye-Sook;Kim, Mi-Yong
    • Journal of East-West Nursing Research
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    • v.12 no.1
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    • pp.43-55
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    • 2006
  • Purpose: This study was a descriptive study to assess the relationships between acculturative stress and current perception of stress in Korean immigrants. Methods: The subjects consisted of 154 community-dwelling Korean immigrant living in the USA. Data collection was conducted through the use of questionnaires. The instruments for this study were Acculturative stress (12 items), The Global Assessment of Recent Scale(8 items). The collected data were analysed using SPSS PC 12.0 Programme for Frequency, Percentage, t-test, ANOVA, Duncan test and Pearson's correlation coefficient according to the purpose of this study. Results: 1) The average item score for acculturative stress was 17.17. The average item score for current perception of stress was 26.56. 2) Acculturative stress was positively related to current perception of stress (r=.360, p<.01). 3) Acculturative stress was significantly different according to educational level (F=2.709, p=.047), occupation (F=16.202, p=.000), perceived income comfort level (F=26.666, p=.000), and type of residence (F=2.672, p=.050). The Current perception of stress was significantly different according to age (F=7.380, p=.000), marital status (F=5.354, p=.006), perceived income comfort level (F=12.738, p=.000), and type of residence(F=4.207, p=.007). Conclusion: Theses findings help to clarify relationships between acculturative stress and current perception of stress in Korean immigrants. Therefore, the result of study provide clues for the quality of life of Korean immigrants.

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