• Title/Summary/Keyword: disease progression

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Crosstalk Signaling between IFN-γ and TGF-β in Microglia Restores the Defective β-amyloid Clearance Pathway in Aging Mice with Alzheimer's Disease

  • Choi, Go-Eun
    • Biomedical Science Letters
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    • v.24 no.4
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    • pp.305-310
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    • 2018
  • Microglia are emerging as critical regulators of innate immune responses in AD and other neurodegenerative disorders, highlighting the importance of understanding their molecular and cellular mechanisms. We attempted to determine the role of crosstalk signaling between $IFN-{\gamma}$ and $TGF-{\beta}$ in $A{\beta}$ clearance by microglia cells. We used in vitro and in vivo mouse models that recapitulated acute and chronic aspects of microglial responses to $A{\beta}$ peptides. We showed that crosstalk signaling between $TGF-{\beta}$ and Smad2 was an important mediator of neuro-inflammation. These findings suggest that microglial $TGF-{\beta}$ activity enhances the pathological progression to AD. As $TGF-{\beta}$ displays broad regulatory effects on beneficial microglial functions, the activation of inflammatory crosstalk signaling between $TGF-{\beta}$ and Smad2 may be a promising strategy to restore microglial functions, halt the progression of $A{\beta}$-driven pathology, and prevent AD development.

Sex Differences in the Preventive Effect of Cardiovascular and Metabolic Therapeutics on Dementia

  • Sun Ah Choi;Hye Jin Jee;Katrina Joy Bormate;Yeonjae Kim;Yi-Sook Jung
    • Biomolecules & Therapeutics
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    • v.31 no.6
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    • pp.583-598
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    • 2023
  • Dementia is a clinical syndrome characterized by progressive impairment of cognitive and functional abilities. As currently applied treatments for dementia can only delay the progression of dementia and cannot fundamentally cure it, much attention is being paid to reducing its incidence by preventing the associated risk factors. Cardiovascular and metabolic diseases are well-known risk factors for dementia, and many studies have attempted to prevent dementia by treating these risk factors. Growing evidence suggests that sex-based factors may play an important role in the pathogenesis of dementia. Therefore, a deeper understanding of the differences in the effects of drugs based on sex may help improve their effectiveness. In this study, we reviewed sex differences in the impact of therapeutics targeting risk factors for dementia, such as cardiovascular and metabolic diseases, to prevent the incidence and/or progression of dementia.

A Genome-Wide Study of Moyamoya-Type Cerebrovascular Disease in the Korean Population

  • Joo, Sung-Pil;Kim, Tae-Sun;Lee, Il-Kwon;Kim, Joon-Tae;Park, Man-Seok;Cho, Ki-Hyun
    • Journal of Korean Neurosurgical Society
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    • v.50 no.6
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    • pp.486-491
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    • 2011
  • Objective : Structural genetic variation, including copy-number variation (CNV), constitutes a substantial fraction of total genetic variability, and the importance of structural variants in modulating susceptibility is increasingly being recognized. CNV can change biological function and contribute to pathophysiological conditions of human disease. Its relationship with common, complex human disease in particular is not fully understood. Here, we searched the human genome to identify copy number variants that predispose to moya-moya type cerebrovascular disease. Methods : We retrospectively analyzed patients who had unilateral or bilateral steno-occlusive lesions at the cerebral artery from March, 2007, to September, 2009. For the 20 subjects, including patients with moyamoya type pathologies and three normal healthy controls, we divided the subjects into 4 groups : typical moyamoya (n=6), unilateral moyamoya (n=9), progression unilateral to typical moyamoya (n=2) and non-moyamoya (n=3). Fragmented DNA was hybridized on Human610Quad v1.0 DNA analysis BeadChips (Illumina). Data analysis was performed with GenomeStudio v2009.1, Genotyping 1.1.9, cnvPartition_v2.3.4 software. Overall call rates were more than 99.8%. Results : In total, 1258 CNVs were identified across the whole genome. The average number of CNV was 45.55 per subject (CNV region was 45.4). The gain/loss of CNV was 52/249, having 4.7 fold higher frequencies in loss calls. The total CNV size was 904,657,868, and average size was 993,038. The largest portion of CNVs (613 calls) were 1M-10M in length. Interestingly, significant association between unilateral moyamoya disease (MMD) and progression of unilateral to typical moyamoya was observed. Conclusion : Significant association between unilateral MMD and progression of unilateral to typical moyamoya was observed. The finding was confirmed again with clustering analysis. These data demonstrate that certain CNV associate with moyamoya-type cerebrovascular disease.

Diagnosis and treatment of Peri-implantitis (Peri-implantitis의 진단 및 치료)

  • Koo, Ki-Tae
    • The Journal of the Korean dental association
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    • v.54 no.4
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    • pp.252-257
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    • 2016
  • This manuscript aims at discussing the technical and biological aspects of peri-implant disease. The following contents will be discussed. -The difference between peri-implantitis and peri-implant mucositis. -Prevalence of peri-implant disease. -Risk factors for peri-implantitis. -Indications and boundaries of non-surgical and surgical treatment -Treatment flow-chart by Schwarz -Limitations of non-surgical treatment -Methods to decontaminate diseased surfaces -Importance of defect configuration in surgical treatment -Biomechanical factors that influence the progression and decontamination related to peri-implantitis -Maintenance of implants.

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A new classification of periodontal and peri-implant disease (치주질환 및 임플란트 주위 질환의 새 분류)

  • Shin, Hyun-Seung
    • The Journal of the Korean dental association
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    • v.57 no.12
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    • pp.758-767
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    • 2019
  • The classification of periodontal disease in 1999 has been widely used for determining a diagnosis, establishing a treatment plan, and evaluating the prognosis of the patient with periodontal disease. However, scientific evidence from many studies indicates the need for a new classification system for periodontal and peri-implant disease. Summary at 2017 world workshop as follows: 1) Periodontal health and peri-implant health was defined; 2) Chronic periodontitis and aggressive periodontitis were unified as periodontitis; 3) Periodontitis was further classified by staging and grading to reflect disease severity and management complexity, rate of disease progression, respectively; 4) Periodontal disease as manifestation of systemic disease is based on the International Statistical Classification of Diseases and Related Health Problems-10 (ICD-10) code; 5) Periodontal biotype and biologic width was replaced to periodontal phenotype and supracrestal tissue attachment, respectively; 6) The excessive occlusal force was replaced by a traumatic occlusal force; 7) ≥3 mm of radiographic bone loss, ≥6 mm of pocket probing depth and bleeding on probing indicates peri-implantitis in the absence of radiograph at final prosthesis delivery.

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Risk Factors for the Development and Progression of Atlantoaxial Subluxation in Surgically Treated Rheumatoid Arthritis Patients, Considering the Time Interval between Rheumatoid Arthritis Diagnosis and Surgery

  • Na, Min-Kyun;Chun, Hyoung-Joon;Bak, Koang-Hum;Yi, Hyeong-Joong;Ryu, Je Il;Han, Myung-Hoon
    • Journal of Korean Neurosurgical Society
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    • v.59 no.6
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    • pp.590-596
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    • 2016
  • Objective : Rheumatoid arthritis (RA) is a systemic disease that can affect the cervical spine, especially the atlantoaxial region. The present study evaluated the risk factors for atlantoaxial subluxation (AAS) development and progression in patients who have undergone surgical treatment. Methods : We retrospectively analyzed the data of 62 patients with RA and surgically treated AAS between 2002 and 2015. Additionally, we identified 62 patients as controls using propensity score matching of sex and age among 12667 RA patients from a rheumatology registry between 2007 and 2015. We extracted patient data, including sex, age at diagnosis, age at surgery, disease duration, radiographic hand joint changes, and history of methotrexate use, and laboratory data, including presence of rheumatoid factor and the C-reactive protein (CRP) level. Results : The mean patient age at diagnosis was 38.0 years. The mean time interval between RA diagnosis and AAS surgery was $13.6{\pm}7.0$ years. The risk factors for surgically treated AAS development were the serum CRP level (p=0.005) and radiographic hand joint erosion (p=0.009). The risk factors for AAS progression were a short time interval between RA diagnosis and radiographic hand joint erosion (p<0.001) and young age at RA diagnosis (p=0.04). Conclusion : The CRP level at RA diagnosis and a short time interval between RA diagnosis and radiographic hand joint erosion might be risk factors for surgically treated AAS development in RA patients. Additionally, a short time interval between RA diagnosis and radiographic hand joint erosion and young age at RA diagnosis might be risk factors for AAS progression.

Proposal on the Process and Prognosis of Popular Diseases (질병의 경과와 예후 판별에 대한 제언)

  • Kwon, Ki-Rok
    • Journal of Pharmacopuncture
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    • v.11 no.1
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    • pp.201-209
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    • 2008
  • Objectives : This study was designed to make beneficial proposal for clinical application on some of the most common disorders treated by Oriental medicine by analyzing treatment process and prognosis. Methods : Number of peculiar attributes pertaining to a specific disorder were analyzed and based on those attributes, patterns associated with process and prognosis were interpreted in reference with classical literatures. Results : 1. Factors which can influence the progression and prognosis include time of onset, intensity of symptoms, course of passage, effects of risk factors, condition of the patient's righteous qi(正氣), accuracy of differential diagnosis made by the practitioner, accuracy of treatment methods, and other unexpected external influences. 2. Correlation between the condition of disorders and treatment progression is closely associated with proper treatment procedures and performances. The time of onset and intensity play critical roles in the treatment process and prognosis and showed pattern tendency with mutual interactions. 3. When there is complication of various disorders, it is ideal to give priority to more urgent illness and take care of moderate illness later. If there isn't any correlation between disorders, treat them in the order of acute to chronic disorders. The approach is reversed when disorders are related, treating in the order of most chronic to most acute. 4. In a case of complication of various disorders, depending on the disorder being acute or chronic, intensity, and accuracy of treatments, either a domino effect or gradual fade out of symptoms were witnessed. 5. The concept of "Five Evils Theory" according to Nan Jing(Difficult Classic) is essential in grasping disease progression due to interrelationships between zangfu organs. Conclusions : Predicting of disease process and prognosis for vast array of disorders treated by Oriental medicine is a very difficult task, yet evaluating the disorder's peculiar properties and influential factors resulted in few principles which can be effectively applied into clinical applications.

Efficacy and Safety of Selumetinib Compared with Current Therapies for Advanced Cancer: a Meta-analysis

  • Shen, Chen-Tian;Qiu, Zhong-Ling;Luo, Quan-Yong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2369-2374
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    • 2014
  • Background and Aim: Selumetinib is a promising and interesting targeted therapy agent as it may reverse radioiodine uptake in patients with radioiodine-refractory differentiated thyroid cancer. We conduct this metaanalysis to compare the efficacy and safety of selumetinib with current therapies in patients with advanced cancer. Methods: An electronic search was conducted using PubMed/ Medicine, EMBASE and Cochrane library databases. Statistical analyses were carried out using either random-effects or fixed-effects models according to the heterogeneity of eligible studies. Results: Six eligible trials involved 601 patients were identified. Compared with current therapies, treatment schedules with selumetinib did not improve progression free survival (hazard ratio, 0.91; 95%CI 0.70-1.17, P= 0.448), but did identify better clinical benefits (odds ratio, 1.24; 95%CI 0.69-2.24, P = 0.472) and less disease progression (hazard ratio, 0.72; 95%CI 0.51-1.00, P = 0.052) though its impact was not statistically significant. Sub-group analysis resulted in significantly improved progression free survival (hazard ratio, 0.61; 95%CI 0.49-0.57, P = 0.00), clinical benefits (odds ratio, 3.04; 95%CI 1.60-5.77, P = 0.001) and reduced disease progression (hazard ratio, 0.35; 95%CI 0.18-0.67, P = 0.001) in patients administrated selumetinib. Dermatitis acneiform (risk ratio, 9.775; 95%CI 3.143-30.395, P = 0.00) and peripheral edema (risk ratio, 2.371; 95%CI 1.690-3.327, P = 0.00) are the most frequently observed adverse effects associated with selumetinib. Conclusions: Compared with current chemotherapy, selumetinib has modest clinical activity as monotherapy in patients with advanced cancer, but combinations of selumetinib with cytotoxic agents in patients with BRAF or KRAS mutations hold great promise for cancer treatment. Dermatitis acneiform and peripheral edema are the most frequently observed adverse effects in patients with selumetinib.

A Study on the Behavior in Patieints with Orafacial Pain by Biobehavioral Pain Profile (Biobehavioral Pain Profile을 이용한 구강안면동통 환자의 행동양식에 관한 연구)

  • Shin, Min
    • Journal of Oral Medicine and Pain
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    • v.23 no.4
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    • pp.403-418
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    • 1998
  • The aim of this study was to measure effects of the following items to pain and pain behavior reaction in patients with chronic orofacial pain. Items that contribute to the first factor(Environmental Influences) measure environmental sources of information that may affect illness behavior; Second factro(Loss of Control) measure appraisals and attributions perceived to influence personal views aobut pain; Third factor(Health Care Avoidance) measures a variety of avoidant behaviors; Fouth factor(Past and Current Experiences) measures experiences with treatment); Fifth factor(Physiological Responsivity) measures physiological parameters that are experienced in association with pain; Sixth factor(Thoughts of Disease Progression) measures thoughts regarding the etiology and progression of disease in relation to pain. 150 patients that were consist of 40 male and 110 female were participated in this study. The obtained results of this study were as follows : 1. Environmental influences and loss of control scales were recorded high score in patients with chronic orofacial pain 2. "Physician's descriptions of what your pain will be like" and "Physician's facial expression when they ask about your pain" items from the environmental influences were recorded high score. These results indicated that responsibility of doctro is very important to the pain reaction behavior of patients. Also, items from thoughts regarding the etiology and progression of disease in relation to pain influenced to the pain reaction. 3. There were significant defferences on the "nurses' descriptions of what you pain will be like", "physician's and nurses' facial expression when they ask about your pain", "TV and radio", and "Literature" items from the environmental influences between male and female patients. 4. There were no significant differences on the each scale between arthrogenous and combitnation group and significant correlated with all 6 scales.

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