• Title/Summary/Keyword: Background variability

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Screening for the 3' UTR Polymorphism of the PXR Gene in South Indian Breast Cancer Patients and its Potential role in Pharmacogenomics

  • Revathidevi, Sundaramoorthy;Sudesh, Ravi;Vaishnavi, Varadharajan;Kaliyanasundaram, Muthukrishnan;MaryHelen, Kilyara George;Sukanya, Ganesan;Munirajan, Arasambattu Kannan
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.8
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    • pp.3971-3977
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    • 2016
  • Background: Breast cancer, the commonest cancer among women in the world, ranks top in India with an incidence rate of 1,45,000 new cases and mortality rate of 70,000 women every year. Chemotherapy outcome for breast cancer is hampered due to poor response and irreversible dose-dependent cardiotoxicity which is determined by genetic variations in drug metabolizing enzymes and transporters. Pregnane X receptor (PXR), a member of the nuclear receptor superfamily, induces expression of drug metabolizing enzymes (DMEs) and transporters leading to regulation of xenobiotic metabolism. Materials and Methods: A genomic region spanning PXR 3' UTR was amplified and sequenced using genomic DNA isolated from 96 South Indian breast cancer patients. Genetic variants observed in our study subjects were queried in miRSNP to establish SNPs that alter miRNA binding sites in PXR 3' UTR. In addition, enrichment analysis was carried out to understand the network of miRNAs and PXR in drug metabolism using DIANA miRpath and miRwalk pathway prediction tools. Results: In this study, we identified SNPs rs3732359, rs3732360, rs1054190, rs1054191 and rs6438550 in the PXR 3; UTR region. The SNPs rs3732360, rs1054190 and rs1054191 were located in the binding site of miR-500a-3p, miR-532-3p and miR-374a-3p resulting in the altered PXR level due to the deregulation of post-transcriptional control and this leads to poor treatment response and toxicity. Conclusions: Genetic variants identified in PXR 3' UTR and their effects on PXR levels through post-transcriptional regulation provide a genetic basis for interindividual variability in treatment response and toxicity associated with chemotherapy.

Hepatitis C Virus - Proteins, Diagnosis, Treatment and New Approaches for Vaccine Development

  • Keyvani, Hossein;Fazlalipour, Mehdi;Monavari, Seyed Hamid Reza;Mollaie, Hamid Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.5917-5935
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    • 2012
  • Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infection and as such is an important global health problem. The virus was discovered in the USA in 1989 and it is now known that three to four million people are infected every year, WHO estimating that 3 percent of the 7 billion people worldwide being chronically infected. Humans are the natural hosts of HCV and this virus can eventually lead to permanent liver damage and carcinoma. HCV is a member of the Flaviviridae family and Hepacivirus genus. The diameter of the virus is about 50-60 nm and the virion contains a single-stranded positive RNA approximately 10,000 nucleotides in length and consisting of one ORF which is encapsulated by an external lipid envelope and icosahedral capsid. HCV is a heterogeneous virus, classified into 6 genotypes and more than 50 subtypes. Because of the genome variability, nucleotide sequences of genotypes differ by approximately 31-34%, and by 20-23% among subtypes. Quasi-species of mixed virus populations provide a survival advantage for the virus to create multiple variant genomes and a high rate of generation of variants to allow rapid selection of mutants for new environmental conditions. Direct contact with infected blood and blood products, sexual relationships and availability of injectable drugs have had remarkable effects on HCV epidemiology. Hundreds of thousands of people die each year from hepatitis and liver cancer caused by HCV virus infection. Approximately 80% of patients with acute hepatitis C progress into a chronic disease state leading to serious hepatic disorders, 10-20% of which develop chronic liver cirrhosis and hepatocellular carcinoma. The incubation period of HCV is 6-8 weeks and the infection is often asymptomatic so it is very hard to detect at early stages, making early treatment very difficult. Therefore, hepatitis C is called a "silent disease". Neutralizing antibodies are produced against several HCV proteins during infection but the virus mutates to escape from antibodies. Some patients with chronic hepatitis C may have some symptoms such as fatigue, muscle aches, nausea and pain. Autoimmune and immunecomplex-mediated diseases have also been reported with chronic HCV infection.

Feasibility Study of Deep Inspiration Breath-Hold Based Volumetric Modulated Arc Therapy for Locally Advanced Left Sided Breast Cancer Patients

  • Swamy, Shanmugam Thirumalai;Radha, Chandrasekaran Anu;Kathirvel, Murugesan;Arun, Gandhi;Subramanian, Shanmuga
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.9033-9038
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    • 2014
  • Background: The purpose of this study was to assess the feasibility of deep inspiration breath-hold (DIBH) based volumetric modulated arc therapy (VMAT) for locally advanced left sided breast cancer patients undergoing radical mastectomy. DIBH immobilizes the tumor bed providing dosimetric benefits over free breathing (FB). Materials and Methods: Ten left sided post mastectomy patients were immobilized in a supine position with both the arms lifted above the head on a hemi-body vaclock. Two thermoplastic masks were prepared for each patient, one for normal free breathing and a second made with breath-hold to maintain reproducibility. DIBH CT scans were performed in the prospective mode of the Varian real time position management (RPM) system. The planning target volume (PTV) included the left chest wall and supraclavicular nodes and PTV prescription dose was 5000cGy in 25 fractions. DIBH-3DCRT planning was performed with the single iso-centre technique using a 6MV photon beam and the field-in-field technique. VMAT plans for FB and DIBH contained two partial arcs ($179^{\circ}-300^{\circ}CCW/CW$). Dose volume histograms of PTV and OAR's were analyzed for DIBH-VMAT, FB-VMAT and DIBH-3DCRT. In DIBH mode daily orthogonal ($0^{\circ}$ and $90^{\circ}$) KV images were taken to determine the setup variability and weekly twice CBCT to verify gating threshold level reproducibility. Results: DIBH-VMAT reduced the lung and heart dose compared to FB-VMAT, while maintaining similar PTV coverage. The mean heart $V_{30Gy}$ was $2.3%{\pm}2.7$, $5.1%{\pm}3.2$ and $3.3%{\pm}7.2$ and for left lung $V_{20Gy}$ was $18.57%{\pm}2.9$, $21.7%{\pm}3.9$ and $23.5%{\pm}5.1$ for DIBH-VMAT, FB-VMAT and DIBH-3DCRT respectively. Conclusions: DIBH-VMAT significantly reduced the heart and lung dose for left side chest wall patients compared to FB-VMAT. PTV conformity index, homogeneity index, ipsilateral lung dose and heart dose were better for DIBH-VMAT compared to DIBH-3DCRT. However, contralateral lung and breast volumes exposed to low doses were increased with DIBH-VMAT.

Result of Voice Analysis after Laryngeal Microsurgery for Vocal Polyp in Elderly (노인에서 성대 용종의 후두 미세수술 후 음성검사 결과)

  • Choi, Jeong-Im;Yeo, Jang-Ok;Jin, Sung-Min;Lee, Sang-Hyuk
    • Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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    • v.22 no.1
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    • pp.47-51
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    • 2011
  • Background and Objectives: Vocal polyps arc one of the most frequent benign laryngeal diseases. They arc usually found at the midpoint of the vocal fold. They are mainly caused by vocal overuse. Vocal polyps arc usually removed surgically. Generally, age-related changes to speech are attributed to change in anatomy and physiology of the speech mechanism. These changes result in increased variability in the acoustic properties of speech with age. Still, not 'all studies of age-related changes in speech have taken differences between the young group and adult group after laryngeal microsurgery into account. The aim of this investigation was to compare improvement of acoustic analysis in young patients and elderly patients with vocal polyps, before and after the laryngeal microsurgery. Materials and Method: One hundred and twenty-eight patients who underwent laryngeal microsurgery for vocal polyps from 2008 through 2011 were reviewed retrospectively. 105 of the 128 patients under age 60 were classified as adult group (AG), and remaining 23 patients as elderly group (EG). The speech of AG and EG were evaluated before and after surgery for identification of differences for age group across measures of fundamental frequency (F0), Jitter, Shimmer and Maximum phonation time (MPT). Results: There were not significant differences between two groups for improvement of F0, Jitter, Shimmer, NHR, and MPT before and after surgery. The findings suggest that elderly group compares quite well with adult group in effectiveness of surgery. However, comparison between elderly group and young group (Age under 40) there was significant difference of improvement in Jitter and Shimmer. Conclusion: In general, the results of the present research showed significant improvement in vocal quality after phonosurgery of vocal polyp in both elderly and adult group. However, comparison of improvement between elderly group and young group, there were significant differences of improvement in jitter and shimmer. Therefore, in treatment planning of elderly group, we should consider age related changes of vocal cord.

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Prediction of Brobchodilator Response by Using $FEF_{25{\sim}75%}$ in Adult Patient with a Normal Spirometry Result (정상 폐활량을 보이는 성인 환자에서 $FEF_{25{\sim}75%}$를 통한 기관지확장제 반응의 예견)

  • Park, Se-Hwan;Lee, Seung-Yup;Kang, Seung-Mo;Seon, Choon-Sik;Kim, Hyun-Kyung;Lee, Byoung-Hoon;Lee, Jae-Hyung;Kim, Sang-Hoon
    • Tuberculosis and Respiratory Diseases
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    • v.71 no.3
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    • pp.188-194
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    • 2011
  • Background: When patients with chronic respiratory symptoms have a normal spirometry result, it is not always easy to consider bronchial asthma as the preferential diagnosis. Forced expiratory flow between 25% and 75% of vital capacity ($FEF_{25{\sim}75%}$) is known as a useful diagnostic value of small airway diseases. However, it is not commonly used, because of its high individual variability. We evaluated the pattern of bronchodilator responsiveness (BDR) and the correlation between $FEF_{25{\sim}75%}$ and BDR in patients with suspicious asthma and normal spirometry. Methods: Among patients with suspicious bronchial asthma, 440 adult patients with a normal spirometry result (forced expiratory volume in one second [$FEV_1$]/forced vital capacity [FVC] ${\geq}70%$ & $FEV_1%$ predicted ${\geq}80%$) were enrolled. We divided this group into a positive BDR group (n=43) and negative BDR group (n=397), based on the result of BDR. A comparison was carried out of spirometric parameters with % change of $FEV_1$ after bronchodilator (${\Delta}FEV_1%$). Results: Among the 440 patients with normal spirometry, $FEF_{25{\sim}75%}%$ predicted were negatively correlated with ${\Delta}FEV_1%$ (r=-0.22, p<0.01), and BDR was positive in 43 patients (9.78%). The means of $FEF_{25{\sim}75%}%$ predicted were $64.0{\pm}14.5%$ in the BDR (+) group and $72.9{\pm}20.8%$ in the BDR (-) group (p<0.01). The negative correlation between $FEF_{25{\sim}75%}%$ predicted and ${\Delta}FEV_1%$ was stronger in the BDR (+) group (r=-0.38, p=0.01) than in the BDR (-) group (r=-0.17, p<0.01). In the ROC curve analysis, $FEF_{25{\sim}75%}$ at 75% of predicted value had 88.3% sensitivity and 40.3% specificity for detecting a positive BDR. Conclusion: BDR (+) was not rare in patients with suspicious asthma and normal spirometry. In these patients, $FEF_{25{\sim}75%}%$ predicted was well correlated with BDR.

The Prognostic Value of the Tumor Shrinkage Rate for Progression-Free Survival in Patients with Non-Small Cell Lung Cancer Receiving Gefitinib

  • Park, Dong Il;Kim, Sun Young;Kim, Ju Ock;Jung, Sung Soo;Park, Hee Sun;Moon, Jae Young;Chung, Chae Uk;Kim, Song Soo;Seo, Jae Hee;Lee, Jeong Eun
    • Tuberculosis and Respiratory Diseases
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    • v.78 no.4
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    • pp.315-320
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    • 2015
  • Background: The efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy can be measured based on the rate of treatment response, based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria or progression-free survival (PFS). However, there are some patients harboring sensitive EGFR mutations who responded poorly to EGFR-TKI therapy. In addition, there is variability in the PFS after EGFR-TKI treatment. Methods: We performed a retrospective analysis of the medical records of 85 patients with non-small cell lung cancer, who had achieved a stable disease or better response at the first evaluation of treatment response, after receiving a 2-month course of gefitinib. We calculated the tumor shrinkage rate (TSR) by measuring the longest and perpendicular diameter of the main mass on computed tomography before, and 2 months after, gefitinib therapy. Results: There was a significant positive correlation between the TSR and PFS (R=0.373, p=0.010). In addition, a simple linear regression analysis showed that the TSR might be an indicator for the PFS ($B{\pm}standard$ error, $244.54{\pm}66.79$; p=0.001). On univariate analysis, the sex, histologic type, smoking history and the number of prior chemotherapy regimens, were significant prognostic factors. On multivariate regression analysis, both the TSR (${\beta}$=0.257, p=0.029) and adenocarcinoma (${\beta}$=0.323, p=0.005) were independent prognostic factors for PFS. Conclusion: Our results showed that the TSR might be an early prognostic indicator for PFS in patients receiving EGFRTKI therapy.

Graduate perception of cosmetic surgery training in plastic surgery residency and fellowship programs

  • Ngaage, Ledibabari Mildred;Kim, Cecelia J;Harris, Chelsea;McNichols, Colton HL;Ihenatu, Chinezimuzo;Rosen, Carly;Elegbede, Adekunle;Gebran, Selim;Liang, Fan;Rada, Erin M;Nam, Arthur;Slezak, Sheri;Lifchez, Scott D;Rasko, Yvonne M
    • Archives of Plastic Surgery
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    • v.47 no.1
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    • pp.70-77
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    • 2020
  • Background As the demand for cosmetic surgery continues to rise, plastic surgery programs and the training core curriculum have evolved to reflect these changes. This study aims to evaluate the perceived quality of current cosmetic surgery training in terms of case exposure and educational methods. Methods A 16-question survey was sent to graduates who completed their training at a U.S. plastic surgery training program in 2017. The survey assessed graduates' exposure to cosmetic surgery, teaching modalities employed and their overall perceived competence. Case complexity was characterized by the minimum number of cases needed by the graduate to feel confident in performing the procedure. Results There was a 25% response rate. The majority of respondents were residents (83%, n=92) and the remaining were fellows (17%, n=18). Almost three quarters of respondents were satisfied with their cosmetic training. Respondents rated virtual training as the most effective learning modality and observing attendings' patients/cases as least effective. Perceived competence was more closely aligned with core curriculum status than case complexity, i.e. graduates feel more prepared for core cosmetic procedures despite being more technically difficult than non-core procedures. Conclusions Despite the variability in cosmetic exposure during training, most plastic surgery graduates are satisfied with their aesthetic training. Incorporation of teaching modalities, such as virtual training, can increase case exposure and allow trainees more autonomy. The recommended core curriculum is adequately training plastic surgery graduates for common procedures and more specialized procedures should be consigned to aesthetic fellowship training.

Development of Data Acquisition System for Quantification of Autonomic Nervous System Activity and It's Clinical Use (자율신경계의 활성도 측정을 위한 Data Acquisition System의 개발 및 임상응용)

  • Shin, Dong-Gu;Park, Jong-Sun;Kim, Young-Jo;Shim, Bong-Sup;Lee, Sang-Hak;Lee, Jun-Ha
    • Journal of Yeungnam Medical Science
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    • v.18 no.1
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    • pp.39-50
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    • 2001
  • Background: Power spectrum analysis method is a powerful noninvasive tool for quantifying autonomic nervous system activity. In this paper, we developed a data acquistion system for estimating the activity of the autonomic nervous system by the analysis of heart rate and respiratory rate variability using power spectrum analysis. Materials and methods: For the detection of QRS peak and measurement of respiratory rate from patient's ECG, we used low-pass filter and impedence method respectively. This system adopt an isolated power for patient's safety. In this system, two output signals can be obtained: R-R interval heart rate) and respiration rate time series. Experimental ranges are 30-240 BPM for ECG and 15-80 BPM for respiration. Results: The system can acquire two signals accurately both in the experimental test using simulator and in real clinical setting. Conclusion: The system developed in this paper is efficient for the acquisition of heart rate and respiration signals. This system will play a role in research area for improving our understanding of the pathophysiologic involvement of the autonomic nervous system in various disease states.

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Classification of Agro-Climatic Zones of the State of Mato Grosso in Brazil (브라질 마토그로소 지역의 농업기후지대 구분)

  • Jung, Myung-Pyo;Park, Hye-Jin;Hur, Jina;Shim, Kyo-Moon;Kim, Yongseok;Kang, Kee-Kyung;Ahn, Joong-Bae
    • Korean Journal of Environmental Agriculture
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    • v.38 no.1
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    • pp.34-37
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    • 2019
  • BACKGROUND: A region can be divided into agroclimatic zones based on homogeneity in weather variables that have greatest influence on crop growth and yield. The agro-climatic zone has been used to identify yield variability and limiting factors for crop growth. This study was conducted to classify agro-climatic zones in the state of Mato Grosso in Brazil for predicting crop productivity and assessing crop suitability etc. METHODS AND RESULTS: For agro-climatic zonation, monthly mean temperature, precipitation, and solar radiation data from Global Modeling and Assimilation Office (GMAO) of National Aeronautics and Space Administration (NASA, USA) between 1980 and 2010 were collected. Altitude and vegetation fraction of Brazil from Weather Research and Forecasting (WRF) were also used to classify them. The criteria of agro-climatic classification were temperature in the hottest month ($30^{\circ}C$), annual precipitation (600 mm and 1000 mm), and altitude (200 m and 500 m). The state of Mato Gross in Brazil was divided into 9 agro-climatic zones according to these criteria by using matrix classification method. CONCLUSION: The results could be useful as information for estimating agro-meteorological characteristics and predicting crop development and crop yield in the state of Mato Grosso in Brazil.

Safety and efficacy of target controlled infusion administration of propofol and remifentanil for moderate sedation in non-hospital dental practice

  • Douglas Lobb;Masoud MiriMoghaddam;Don Macalister;David Chrisp;Graham Shaw;Hollis Lai
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.23 no.1
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    • pp.19-28
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    • 2023
  • Background: Fearful and anxious patients who find dental treatment intolerable without sedative and analgesic support may benefit from moderate sedation. Target controlled infusion (TCI) pumps are superior to bolus injection in maintaining low plasma and effect-site concentration variability, resulting in stable, steady-state drug concentrations. We evaluated the safety and efficacy of moderate sedation with remifentanil and propofol using TCI pumps in non-hospital dental settings. Methods: A prospective chart review was conducted on 101 patients sedated with propofol and remifentanil using TCI pumps. The charts were completed at two oral surgeons and one general dentist's office over 6 months. Hypoxia, hypotension, bradycardia, and over-sedation were considered adverse events and were collected using Tracking and Reporting Outcomes of Procedural Sedation (TROOPS). Furthermore, patient recovery time, sedation length, drug dose, and patient satisfaction questionnaires were used to measure sedation effectiveness. Results: Of the 101 reviewed sedation charts, 54 were of men, and 47 were of women. The mean age of the patients was 40.5 ±18.7 years, and their mean BMI was 25.6 ± 4.4. The patients did not experience hypoxia, bradycardia, and hypotension during the 4694 min of sedation. The average minimum Mean Arterial Pressure (MAP) and heartbeats were 75.1 mmHg and 60.4 bpm, respectively. 98% of patients agreed that the sedation technique met their needs in reducing their anxiety, and 99% agreed that they were satisfied with the sedation 24 hours later. The average sedation time was 46.9 ± 55.6 min, and the average recovery time was 12.4 ± 4.4 min. Remifentanil and propofol had mean initial effect-site concentration doses of 0.96 µ/.ml and 1.0 ng/ml respectively. The overall total amount of drug administered was significantly higher in longer sedation procedures compared to shorter ones, while the infusion rate decreased as the procedural stimulus decreased. Conclusion: According to the results of this study, no patients experienced adverse events during sedation, and all patients were kept at a moderate sedation level for a wide range of sedation times and differing procedures. The results showed that TCI pumps are safe and effective for administering propofol and remifentanil for moderate sedation in dentistry.