• Title/Summary/Keyword: treatment failure

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KR-39038, a Novel GRK5 Inhibitor, Attenuates Cardiac Hypertrophy and Improves Cardiac Function in Heart Failure

  • Lee, Jeong Hyun;Seo, Ho Won;Ryu, Jae Yong;Lim, Chae Jo;Yi, Kyu Yang;Oh, Kwang-Seok;Lee, Byung Ho
    • Biomolecules & Therapeutics
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    • v.28 no.5
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    • pp.482-489
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    • 2020
  • G protein-coupled receptor kinase 5 (GRK5) has been considered as a potential target for the treatment of heart failure as it has been reported to be an important regulator of pathological cardiac hypertrophy. To discover novel scaffolds that selectively inhibit GRK5, we have identified a novel small molecule inhibitor of GRK5, KR-39038 [7-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-2-(2-chlorophenyl)-6-fluoroquinazolin-4(3H)-one]. KR-39038 exhibited potent inhibitory activity (IC50 value=0.02 µM) against GRK5 and significantly inhibited angiotensin II-induced cellular hypertrophy and HDAC5 phosphorylation in neonatal cardiomyocytes. In the pressure overload-induced cardiac hypertrophy mouse model, the daily oral administration of KR-39038 (30 mg/kg) for 14 days showed a 43% reduction in the left ventricular weight. Besides, KR-39038 treatment (10 and 30 mg/kg/day, p.o.) showed significant preservation of cardiac function and attenuation of myocardial remodeling in a rat model of chronic heart failure following coronary artery ligation. These results suggest that potent GRK5 inhibitor could effectively attenuate both cardiac hypertrophy and dysfunction in experimental heart failure, and KR-39038 may be useful as an effective GRK5 inhibitor for pharmaceutical applications.

Application and Potential of Artificial Intelligence in Heart Failure: Past, Present, and Future

  • Minjae Yoon;Jin Joo Park;Taeho Hur;Cam-Hao Hua;Musarrat Hussain;Sungyoung Lee;Dong-Ju Choi
    • International Journal of Heart Failure
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    • v.6 no.1
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    • pp.11-19
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    • 2024
  • The prevalence of heart failure (HF) is increasing, necessitating accurate diagnosis and tailored treatment. The accumulation of clinical information from patients with HF generates big data, which poses challenges for traditional analytical methods. To address this, big data approaches and artificial intelligence (AI) have been developed that can effectively predict future observations and outcomes, enabling precise diagnoses and personalized treatments of patients with HF. Machine learning (ML) is a subfield of AI that allows computers to analyze data, find patterns, and make predictions without explicit instructions. ML can be supervised, unsupervised, or semi-supervised. Deep learning is a branch of ML that uses artificial neural networks with multiple layers to find complex patterns. These AI technologies have shown significant potential in various aspects of HF research, including diagnosis, outcome prediction, classification of HF phenotypes, and optimization of treatment strategies. In addition, integrating multiple data sources, such as electrocardiography, electronic health records, and imaging data, can enhance the diagnostic accuracy of AI algorithms. Currently, wearable devices and remote monitoring aided by AI enable the earlier detection of HF and improved patient care. This review focuses on the rationale behind utilizing AI in HF and explores its various applications.

Study on the Reliability of Engineering Ceramics (구조용 세라믹스 강도의 신뢰성 평가에 관한 연구)

  • 김부안;남기우
    • Journal of the Korean Ceramic Society
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    • v.34 no.2
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    • pp.157-162
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    • 1997
  • Silicon Nitride samples with different microstructure were prepared by hot pressing and subsequent heat treatment under N2 gas pressure. The fracture toughness (KIC)of Si3N4 increased with the increase of grain size, but the bending strength of plain specimen($\sigma$F) decreased. The relation between fracture stress($\sigma$c) and equivalent crack length(ae) agreed well with the calculated values by process zone size failure criterion. A probabilistic failure assessment curve is proposed based on both statistical character of $\sigma$F and KIC.

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Ejaculatory Failure after Unilateral Neurolytic Celiac Plexus Block

  • Shin, Seo-Kyung;Kweon, Tae-Dong;Ha, Sang-Hee;Yoon, Kyung-Bong
    • The Korean Journal of Pain
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    • v.23 no.4
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    • pp.274-277
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    • 2010
  • Abdominal pain associated with chronic pancreatitis is often difficult to control with analgesics and can be severely debilitating with significant impairment of quality of life. In these patients, neurolytic celiac plexus block (NCPB) is an effective treatment option with a low complication rate. However, there is a risk of ejaculatory failure after NCPB, which may be a problem in patients with a long life expectancy. We report a case of ejaculatory failure after unilateral NCPB in a patient with chronic pancreatitis.

Effects of the Cultivated Fruit Body of Phellinus linteus on Mercuric chloride-induced Renal Failure (배양상황버섯 자실체의 승홍투여로 유도된 흰쥐 신기능에 미치는 영향)

  • 양기숙;정은주;표명윤
    • YAKHAK HOEJI
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    • v.46 no.3
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    • pp.174-178
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    • 2002
  • Phellinus linteus (Hymenocaetaceae) is a member of Basidiomycotinae, which has been used for the treatment of gastric cancer, non-insulin-dependent diabetes mellitus, diarrhea, and menstrual irregularity. To investigate the diuretic action of Phellinus linteus, urinary volume, serum parameters and urinary electrolytes in HgCl$_2$-induced acute renal failure rats in vivo were measured. The results showed that its MeOH extract produced significant increases on urinary volume, sodium and potassium excretion, and revealed lowering effects of the abnormally elevated BUN, creatinine and uric acid value in acute renal failure rats.

A Probabilistic based Systems Approach to Reliability Prediction of Solid Rocket Motors

  • Moon, Keun-Hwan;Gang, Jin-Hyuk;Kim, Dong-Seong;Kim, Jin-Kon;Choi, Joo-Ho
    • International Journal of Aeronautical and Space Sciences
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    • v.17 no.4
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    • pp.565-578
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    • 2016
  • A probabilistic based systems approach is addressed in this study for the reliability prediction of solid rocket motors (SRM). To achieve this goal, quantitative Failure Modes, Effects and Criticality Analysis (FMECA) approach is employed to determine the reliability of components, which are integrated into the Fault Tree Analysis (FTA) to obtain the system reliability. The quantitative FMECA is implemented by burden and capability approach when they are available. Otherwise, the semi-quantitative FMECA is taken using the failure rate handbook. Among the many failure modes in the SRM, four most important problems are chosen to illustrate the burden and capability approach, which are the rupture, fracture of the case, and leak due to the jointed bolt and O-ring seal failure. Four algorithms are employed to determine the failure probability of these problems, and compared with those by the Monte Carlo Simulation as well as the commercial code NESSUS for verification. Overall, the study offers a comprehensive treatment of the reliability practice for the SRM development, and may be useful across the wide range of propulsion systems in the aerospace community.

Nonlinear dynamics and failure wind velocity analysis of urban trees

  • Ai, Xiaoqiu;Cheng, Yingyao;Peng, Yongbo
    • Wind and Structures
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    • v.22 no.1
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    • pp.89-106
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    • 2016
  • With an aim to assess the wind damage to urban trees in more realistic conditions, the nonlinear dynamics of structured trees subjected to strong winds with different levels is investigated in the present paper. For the logical treatment of dynamical behavior of trees, material nonlinearities of green wood associated with tree biomechanics and geometric nonlinearity of tree configuration are included. Applying simulated fluctuating wind velocity to the numerical model, the dynamical behavior of the structured tree is explored. A comparative study against the linear dynamics analysis usually involved in the previous researches is carried out. The failure wind velocity of urban trees is then defined, whereby the failure percentages of the tree components are exposed. Numerical investigations reveal that the nonlinear dynamics analysis of urban trees results in a more accurate solution of wind-induced response than the classical linear dynamics analysis, where the nonlinear effect of the tree behavior gives rise to be strengthened as increasing of the levels of wind velocity, i.e., the amplitude of 10-min mean wind velocity. The study of relationship between the failure percentage and the failure wind velocity provides a new perspective towards the vulnerability assessment of urban trees likely to fail due to wind actions, which is potential to link with the practical engineering.

Factors Related to N-Terminal Pro-B-Type Natriuretic Peptide as a Biomarker for Heart Failure

  • Lee, Hyeong Suk;Choi, Mona;Oh, Eui Geum
    • Journal of Korean Biological Nursing Science
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    • v.18 no.4
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    • pp.247-256
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    • 2016
  • Purpose: This study aimed to examine the relationships between the N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels with the sociodemographic and clinical factors, self-care behaviors, and the physical symptom experiences in patients with heart failure. Methods: This cross-sectional study utilized a convenience sample of adult outpatients and inpatients who attended a cardiology department in a tertiary hospital in Seoul, Korea. The data from 154 patients with heart failure were collected using a questionnaire, and their clinical data were extracted from their electronic medical records. Results: Compared with the patients with high NT-proBNP levels, those with low NT-proBNP levels had significantly lower physical symptom experiences scores. Patients with low- and mid-NT-proBNP levels were more likely to be employed compared with those with high NT-proBNP levels. Patients with low NT-proBNP levels had higher left ventricular ejection fractions, and were less likely to have arrhythmias and comorbidities. Conclusion: The results from this study showed that patients with more severe heart failure had higher physical symptom experiences scores; hence, individualizing treatment approaches based on heart failure severity is necessary.

Clinical trial study for failure to thrive in recent journals of Traditional Chinese Medicine (성장 장애에 관한 임상 연구의 최근 동향 -최근 중의 잡지를 중심으로-)

  • Lee, Ji-Young;Jeong, Min-Jeong;Choi, Ji-Myuoung;Yu, Sun-Ae;Lee, Seung-Yeon
    • The Journal of Pediatrics of Korean Medicine
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    • v.21 no.1
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    • pp.155-171
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    • 2007
  • Objectives : The aim of this study was to investigate the treatment of failure to thrive in current Traditional Chinese Medical Journals. Methods : To figure out the failure to thrive, Chinese Medical Journals from China National Knowledge Infrastructure(CNKI) which was published in 1994 to 2005 were analyzed. 矮(小)-whae(so) was searched. Results : Eleven articles were selected. 5 of them were used herbal medicine, and were showed that the total improvement rate was higher than 70% in failure to thrive. 2 of them were used acupuncture, and the last of them were used a therapy of combining Traditional Chinese Medicine with western medicine. Conclusions : The Oriental medical treatments for failure to thrive were presumed to be effective in most articles. But we think that the more studies are needed.

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A Case Report of Climacteric Symptoms in Premature Ovarian Failure Patient Who Has One Side Ovariectomy and Pelvic Tuberculosis (골반결핵과 단측 난소절제의 병력이 있는 환자의 조기 폐경 후 갱년기 증상 치험 1례)

  • Lee, Yeon-Kyeong;Yoo, Yung-Ki;Lee, Dong-Nyung;Kim, Hyung-Jun
    • The Journal of Korean Obstetrics and Gynecology
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    • v.21 no.3
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    • pp.269-278
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    • 2008
  • Purpose: The purpose of this study is to report the effect of Traditional Korean Medicine therapy on climacteric symptoms in premature ovarian failure patient. Methods: The patient in this case was 32 years old female. She had a history of the right side ovariectomy and antituberculous chemoteraphy caused by pelvic tuberculosis. And she was diagnosed with premature ovarian failure in October, 2007. She had a climacteric symptoms when she admitted to the OBGY department of Se-Myung University in Je-Cheon. She received Korean Medicine therapies such as herbal medicine, moxibustion, acupuncture. We evaluated patient's health status by Kupperman's index and VAS. Results: After the treatment, the climacteric symptoms in premature ovarian failure patient was improved. Conclusion: This case study shows that Korean Medicine therapies have significant effect on climacteric symptoms in premature ovarian failure.

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