54 results on '"Tran DC"'
Search Results
2. Sexual Activities and Fear-related Reasons for Avoiding Sexual Activities in Early Pregnancy: A Cross-sectional Study
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Phan, CT, Tran, DC, Hoang, BL, Tran, KT, Pham, TTT, Thi, H Dao, Van, T Ngo, and Viet, A Bui
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- 2022
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3. Clinical Pharmacology Aspects of Sex-Related Drug Products
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Lee L, Apparaju S, Kim H, Tran Dc, Myong-Jin Kim, and Yu C
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Male ,Drug ,medicine.medical_specialty ,media_common.quotation_subject ,Phases of clinical research ,Pharmacology ,law.invention ,Pharmacokinetics ,law ,Humans ,Medicine ,Pharmacology (medical) ,Intensive care medicine ,Drug Approval ,Drug Labeling ,media_common ,Clinical pharmacology ,United States Food and Drug Administration ,business.industry ,Sex related ,Drugs, Investigational ,United States ,Pre-clinical development ,Sexual Dysfunction, Physiological ,Drug development ,Pharmacogenomics ,Female ,business - Abstract
Clinical pharmacology plays an important role in drug development, including evaluation of a drug's pharmacokinetics (PK), interaction potential, exposure-response relationship, and pharmacogenomics (Table 1). Reviewers in the Office of Clinical Pharmacology at the US Food and Drug Administration (FDA) consider these issues to facilitate drug development and to ensure that drug products are safe and effective. This article highlights some of the important clinical pharmacology topics in the development of sex-related drug products.
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- 2011
4. Haematopoietic regeneration by HLA-A*0206-deficient clones in severe aplastic anaemia without definitive immunosuppressive treatment.
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Zaimoku Y, Sakai K, Tsuji N, Hosomichi K, Yamada S, Tran DC, Kobayashi M, Sugiyama A, Hirayasu K, Mizumaki H, Ishiyama K, Hanayama R, Tomiyama Y, and Nakao S
- Abstract
We describe the case of a 74-year-old man with severe aplastic anaemia who experienced persistent remission attributed to proliferation of HLA allele-deficient clones. Despite an initial worsening of pancytopenia with eltrombopag and ciclosporin treatment, gradual trilineage haematopoietic recovery occurred, with blood counts normalizing over 3 years. Flow cytometry and deep nucleotide sequencing revealed that haematopoiesis was primarily supported by several clones with somatic mutations that inactivated antigen presentation via HLA-A*0206. This suggests that monitoring haematopoietic regeneration by immune escape clones could be an alternative approach for immune aplastic anaemia patients who possess HLA allele-deficient clones and cannot tolerate standard therapy., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2024
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5. Impact of proximity of left atrium to descending aorta on left inferior pulmonary vein triggers or drivers of atrial fibrillation: A risk score model.
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Bautista JAL, Liu CM, Ibrahim AE, Lo LW, Chung FP, Hu YF, Chang SL, Lin YJ, Lin CY, Chang TY, Kuo L, Liu SH, Cheng WH, Chen WT, Kao PH, Kuo MJ, Nguyen-Khac TC, Li GY, Lin CH, Huang YS, Wu SJ, Siow YK, Son Nguyen ND, Tran DC, and Chen SA
- Abstract
Background: Prior studies have investigated cardiac anatomy and clinical parameters as predictors for pulmonary vein and non-pulmonary vein triggers., Objective: We aimed to assess the link between the descending aorta to left inferior pulmonary vein (Dao-LIPV) distance and the occurrence of triggers and drivers in atrial fibrillation (AF) ablation procedures., Methods: Drug-refractory AF patients who underwent first-time index catheter ablation from January 2010 to December 2019 were retrospectively assembled. The Dao-LIPV distance was measured from preablation pulmonary vein computed tomography. Patients were assigned to groups on the basis of the presence of LIPV triggers or drivers. Multivariate logistic regression was used to identify risk factors., Results: A total of 886 consecutive patients with drug-refractory AF were studied, and 63 (7.1%) patients were identified to have LIPV triggers or drivers. The Dao-LIPV distance had a better predictive performance (area under the curve, 0.70) compared with persistent AF (area under the curve, 0.57). Multivariate logistic regression analysis showed that Dao-LIPV distance ≤2.5 mm (odds ratio, 3.96; 95% CI, 2.15-7.29; P < .001) and persistent AF (odds ratio, 1.73; 95% CI, 1.02-2.94]; P = .044) were independent predictors for the presence of LIPV triggers or drivers. A risk score model was established to predict the probability of LIPV triggers or drivers with persistent AF (10.2%), Dao-LIPV distance ≤2.5 mm (11.4%), and both (15.0%)., Conclusion: The proximity of the Dao-LIPV was correlated to the presence of LIPV triggers or drivers. We developed a risk score model indicating that persistent AF and Dao-LIPV distances ≤2.5 mm significantly increase the risk of LIPV triggers or drivers, aiding electrophysiologists in preparing for and performing catheter ablation more effectively., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)
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- 2024
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6. Effect of AGTR1 A1166C genetic polymorphism on coronary artery lesions and mortality in patients with acute myocardial infarction.
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Tran DC, Le LHG, Thai TT, Van Hoang S, Do MD, and Truong BQ
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- Humans, Male, Middle Aged, Aged, Female, Constriction, Pathologic, Prospective Studies, Polymorphism, Genetic, Receptor, Angiotensin, Type 1 genetics, Coronary Vessels, Myocardial Infarction genetics
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The pathogenesis and prognosis of patients with acute myocardial infarction (AMI) may be influenced by both genetic and environmental factors. Findings on the relationship of polymorphisms in various genes encoding the renin-angiotensin-aldosterone system with coronary artery lesions and mortality in AMI patients are inconsistent. The aim of this study was to determine whether the AGTR1 A1166C genetic polymorphism affects coronary artery lesions and 1-year mortality in post-AMI patients. Patients with their first AMI admitted to Cho Ray Hospital, Vietnam, from January 2020 to August 2021 were enrolled in this prospective clinical study. All participants underwent invasive coronary angiography and were identified as having the genotypes of AGTR1 A1166C by way of a polymerase chain reaction method. All patients were followed up for all-cause mortality 12 months after AMI. The association of the AGTR1 A1166C polymorphism with coronary artery lesions and 1-year mortality was evaluated using logistic regression and Cox regression analysis, respectively. Five hundred and thirty-one AMI patients were recruited. The mean age was 63.9 ± 11.6 years, and 71.6% of the patients were male. There were no significant differences in the location and number of diseased coronary artery branches between the AA and AC+CC genotypes. The AC and CC genotypes were independently associated with ≥ 90% diameter stenosis of the left anterior descending (LAD) artery (odds ratio = 1.940; 95% confidence interval (CI): 1.059-3.552, p = 0.032). The 1-year all-cause mortality rate difference between patients with the AC and CC genotypes versus those with the AA genotype was not statistically significant (hazard ratio = 1.000, 95% CI: 0.429-2.328, p = 1.000). The AGTR1 A1166C genetic polymorphism is associated with very severe luminal stenosis of the LAD but not with mortality in AMI patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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7. Case report: Immune pressure on hematopoietic stem cells can drastically expand glycosylphosphatidylinositol-deficient clones in paroxysmal nocturnal hemoglobinuria.
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Shingai N, Mizumaki H, Najima Y, Yamada Y, Tran DC, Haraguchi K, Toya T, Okuyama Y, Doki N, Nannya Y, Ogawa S, and Nakao S
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- Female, Humans, Adult, Glycosylphosphatidylinositols genetics, Hematopoietic Stem Cells metabolism, Clone Cells metabolism, Hemoglobinuria, Paroxysmal diagnosis, Anemia, Aplastic genetics, Anemia, Aplastic complications
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Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disease characterized by intravascular hemolysis, thrombosis, and bone marrow (BM) failure. Although PNH is caused by excessive proliferation of hematopoietic stem cell (HSC) clones with loss of function mutations in phosphatidylinositol N-acetylglucosaminyltransferase subunit A ( PIGA ) genes, what drives PNH clones to expand remains elusive., Case Description: We present a case of a 26-year-old female who presented with hemolytic anemia, thrombocytopenia, and leukopenia. Flow cytometry analysis of peripheral blood showed that 71.9% and 15.3% of the granulocytes and erythrocytes were glycosylphosphatidylinositol-anchored protein deficient (GPI[-]) cells. The patient was diagnosed with PNH with non-severe aplastic anemia. Deep-targeted sequencing covering 390 different genes of sorted GPI(-) granulocytes revealed three different PIGA mutations (p.I69fs, variant allele frequency (VAF) 24.2%; p.T192P, VAF 5.8%; p.V300fs, VAF 5.1%) and no other mutations. She received six cycles of eculizumab and oral cyclosporine. Although the patient's serum lactate dehydrogenase level decreased, she remained dependent on red blood cell transfusion. Six months after diagnosis, she received a syngeneic bone marrow transplant (BMT) from a genetically identical healthy twin, following an immune ablative conditioning regimen consisting of cyclophosphamide 200 mg/kg and rabbit anti-thymocyte globulin 10 mg/kg. After four years, the patient's blood count remained normal without any signs of hemolysis. However, the peripheral blood still contained 0.2% GPI (-) granulocytes, and the three PIGA mutations that had been detected before BMT persisted at similar proportions to those before transplantation (p.I69fs, VAF 36.1%; p.T192P, VAF 3.7%; p.V300fs, VAF 8.6%) in the small PNH clones that persisted after transplantation., Conclusions: The PNH clones that had increased excessively before BMT decreased, but persisted at low percentages for more than four years after the immunoablative conditioning regimen followed by syngeneic BMT. These findings indicate that as opposed to conventional theory, immune pressure on HSCs, which caused BM failure before BMT, was sufficient for PIGA -mutated HSCs to clonally expand to develop PNH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shingai, Mizumaki, Najima, Yamada, Tran, Haraguchi, Toya, Okuyama, Doki, Nannya, Ogawa and Nakao.)
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- 2024
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8. Ventricular arrhythmias originating from left ventricular summit: Salvage strategies after conventional ablation.
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Tran DC and Chung FP
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Competing Interests: Authors declare no conflict of interests for this article.
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- 2024
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9. The genetic landscape of chromosomal aberrations in 3776 Vietnamese fetuses with clinical anomalies during pregnancy.
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Tran DC, Phan MN, Dao HT, Nguyen HL, Nguyen DA, Le QT, Hoang DT, Tran NT, Thi Ha TM, Dinh TL, Nguyen CC, Thi Doan KP, Thi Luong LA, Vo TS, Nhat Trinh TH, Nguyen VT, Vo PN, Nguyen YN, Dinh MA, Doan PL, Do TT, Nguyen QT, Truong DK, Nguyen HN, Phan MD, Tang HS, and Giang H
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- Humans, Female, Pregnancy, Vietnam, Adult, Retrospective Studies, Prenatal Diagnosis methods, Aneuploidy, Asian People genetics, Ultrasonography, Prenatal methods, Southeast Asian People, DNA Copy Number Variations genetics, Chromosome Aberrations, Fetus
- Abstract
Background: Copy number variation sequencing (CNV-seq) is a powerful tool to discover structural genomic variation, but limitations associated with its retrospective study design and inadequate diversity of participants can be impractical for clinical application. Aim: This study aims to use CNV-seq to assess chromosomal aberrations in pregnant Vietnamese women. Materials & methods: A large-scale study was conducted on 3776 pregnant Vietnamese women with abnormal ultrasound findings. Results: Chromosomal aberrations were found in 448 (11.86%) women. Of these, 274 (7.26%) had chromosomal aneuploidies and 174 (4.61%) carried pathogenic/likely pathogenic CNVs. Correlations were established between chromosomal aberrations and various phenotypic markers. Conclusion: This comprehensive clinical study illuminates the pivotal role of CNV-seq in prenatal diagnosis for pregnancies featuring fetal ultrasound anomalies.
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- 2024
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10. High prevalence of maternal mosaic monosomy X in pregnant women in Vietnam.
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Tran DC, Nguyen TT, Thi Hoang NL, Thi Luong LA, Doan KT, Ha MTT, Tran NT, Nguyen VT, Trinh TN, Kieu Nguyen NT, Nguyen CT, Nguyen TD, Thi Nguyen XT, Do TT, Truong DK, Giang H, Nguyen HN, Tang HS, and Phan MD
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- Pregnancy, Female, Humans, Pregnant Women, In Situ Hybridization, Fluorescence, Vietnam epidemiology, Prevalence, Prenatal Diagnosis methods, Turner Syndrome diagnosis, Turner Syndrome epidemiology, Turner Syndrome genetics
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Objective: To demonstrate the prevalence of maternal mosaic monosomy X (MMXO) in a cohort of pregnant women in Vietnam., Methods: All 105,594 singleton pregnant women undergoing noninvasive prenatal screening (NIPS) between January 2019 and February 2021 in Vietnam were analyzed by measuring discordance between size- and count-based z-scores for chromosome X (ChrX) to identify suspected cases of MMXO and validated by fluorescence in situ hybridization (FISH) on maternal blood., Results: We identified 295 (0.279%) suspected MMXO cases. After FISH analysis, MMXO was confirmed in 125 cases (42.37%), revealing the MMXO prevalence of 0.118% (95% CI: 0.097-0.139%) in this cohort., Conclusion: We found a relatively high prevalence of MMXO in Vietnamese pregnant women and demonstrated a strong influence of MMXO on the ChrX z-score using a count-based method, resulting in false positives. The size-based method is not sensitive to MMXO and therefore achieves higher PPV.
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- 2023
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11. Minor GPI(-) granulocyte populations in aplastic anemia and healthy individuals derived from a few PIGA-mutated hematopoietic stem progenitor cells.
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Mizumaki H, Tran DC, Hosokawa K, Hosomichi K, Zaimoku Y, Takamatsu H, Yamazaki H, Ishiyama K, Yamazaki R, Fujiwara H, Tajima A, and Nakao S
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- Humans, Stem Cells, Anemia, Aplastic genetics
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- 2023
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12. De novo variants of dominant monogenic disorders in Vietnam detected by a noninvasive prenatal test: a case series.
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Tran NT, Vo ST, Nguyen DA, Nguyen CC, Dinh LT, Tran MT, Tran DC, Luong LT, Doan KP, Huy Nguyen VQ, Thi Ha TM, Truong LT, Cao PT, Tran VT, Nhut Trinh TH, Le QT, Nguyen VT, Hoang DT, Nguyen MB, Bui CT, Tran ST, Lam DT, Le HT, Nguyen MB, Ho VT, Nguyen MT, Dao TT, Nguyen PM, Nguyen TL, Ha NP, Lu YT, Do TT, Truong DK, Phan MD, Nguyen HN, Giang H, and Tang HS
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- Pregnancy, Female, Humans, Vietnam, Receptor, Fibroblast Growth Factor, Type 3, Prenatal Diagnosis, Thanatophoric Dysplasia diagnosis, Thanatophoric Dysplasia genetics
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Background: Noninvasive prenatal tests for monogenic diseases (NIPT-SGG) have recently been reported as helpful in early-stage antenatal screening. Our study describes the clinical and genetic features of cases identified by NIPT-SGG. Materials & methods: In a cohort pregnancy with abnormal sonograms, affected cases were confirmed by invasive diagnostic tests concurrently, with NIPT-SGG targeting 25 common dominant single-gene diseases. Results: A total of 13 single-gene fetuses were confirmed, including Noonan and Costello syndromes, thanatophoric dysplasia, achondroplasia, osteogenesis imperfecta and Apert syndrome. Two novel variants seen were tuberous sclerosis complex ( TSC2 c.4154G>A) and Alagille syndrome ( JAG1 c.3452del). Conclusion: NIPT-SGG and standard tests agree on the results for 13 fetuses with monogenic disorders. This panel method of screening can benefit high-risk Vietnamese pregnancies, but further research is encouraged to expand on the causative gene panel.
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- 2023
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13. Clinical significance of substrate characteristics and ablation outcomes in patients with atrial fibrillation and significant functional mitral regurgitation.
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Bautista JAL, Lin CY, Lu CT, Lo LW, Lin YJ, Chang SL, Hu YF, Chung FP, Tuan TC, Chao TF, Liao JN, Chang TY, Kuo L, Liu CM, Liu SH, Wu CI, Kuo MJ, Li GY, Huang YS, Wu SJ, Siow YK, Son NND, Tran DC, and Chen SA
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Background: Atrial fibrillation (AF) and mitral regurgitation (MR) have a complex interplay. Catheter ablation (CA) of AF may be a potential method to improve the severity of MR in AF patients., Methods: Patients with symptomatic AF and moderate to severe MR who underwent catheter ablation from 2011 to 2021 were retrospectively included in the study. Patients' baseline characteristics and electrophysiological features were examined. These patients were classified as group 1 with improved MR and group 2 with refractory MR after CA., Results: Fifty patients (age 60.2 ± 11.6 years, 29 males) were included in the study (32 in group 1 and 18 in group 2). Group 1 patients had a lower CHA
2 DS2 -VASc score (1.7 ± 1.5 vs. 2.7 ± 1.5, P = 0.005) and had a lower incidence of hypertension (28.1% vs. 66.7%, P = 0.007) and diabetes mellitus (3.1% vs. 22.2%, P = 0.031) as compared to group 2 patients. Electroanatomic three-dimensional (3D) mapping showed that group 1 patients demonstrated less scars on the posterior bottom of the left atrium compared to group 2 patients (12.5% vs. 66.7%, P < 0.001). AF recurrence was not different between the two groups. After multivariate logistic regression analysis, a posterior bottom scar in the left atrium independently predicted refractory MR despite successful AF ablation., Conclusion: Most patients with AF and MR showed improvement of MR after AF ablation. A scar involving the posterior bottom of the left atrium is associated with poor recovery of MR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Bautista, Lin, Lu, Lo, Lin, Chang, Hu, Chung, Tuan, Chao, Liao, Chang, Kuo, Liu, Liu, Wu, Kuo, Li, Huang, Wu, Siow, Son, Tran and Chen.)- Published
- 2023
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14. Developing and validating noninvasive prenatal testing for de novo autosomal dominant monogenic diseases in Vietnam.
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Nguyen NY, Lu YT, Nguyen DA, Nguyen CC, Dinh LT, Tran MT, Tran DC, Luong LT, Doan KP, Huy Nguyen VQ, Thi Ha TM, Truong LT, Tran NT, Cao PT, Tran VT, Nhut Trinh TH, Le QT, Nguyen VT, Hoang DT, Vo ST, Nguyen MB, Bui CT, Tran ST, Lam DT, Le HT, Nguyen MB, Ho VT, Nguyen MT, Doan PL, Tran KT, Tran HT, Tran UV, Dinh AM, Nguyen TT, Do TT, Truong DK, Phan MD, Nguyen HN, Tang HS, and Giang H
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- Pregnancy, Female, Infant, Newborn, Humans, Vietnam, Prenatal Diagnosis, Noninvasive Prenatal Testing
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Background: Over 60% of single-gene diseases in newborns are autosomal dominant variants. Noninvasive prenatal testing for monogenic conditions (NIPT-SGG) is cost-effective and timesaving, but not widely applied. This study introduces and validates NIPT-SGG in detecting 25 monogenic conditions. Methods: NIPT-SGG with a 30-gene panel applied next-generation sequencing and trio assays to confirm de novo variants. Diagnostic tests confirmed NIPT-detected cases. Results: Among 93 pregnancies with ultrasound findings, 11 (11.8%) fetuses were screened and diagnosed with monogenic diseases, mostly with Noonan syndrome. NIPT-SGG determined >99.99% of actual positive and negative cases, confirmed by diagnostic tests. No false-negatives or false-positives were reported. Conclusion: NIPT-SGG effectively identifies the fetuses affected with monogenic diseases, which is a promisingly safe and timely antenatal screening option for high-risk pregnancies.
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- 2023
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15. Predictive value of ACE I/D genetic polymorphism for 12-month all-cause mortality in patients with acute myocardial infarction.
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Tran DC, Do MD, Le LHG, Thai TT, Hoang SV, and Truong BQ
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- Humans, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Prospective Studies, Polymorphism, Genetic, Angiotensin Receptor Antagonists, Myocardial Infarction genetics
- Abstract
The prognostic role of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) genetic polymorphism in patients with acute myocardial infarction (AMI) is controversial and inconsistent across various study populations. This study evaluated the predictive validity of the ACE I/D variant based on 12-month all-cause mortality in Vietnamese patients after AMI. This was an observational, prospective study conducted among AMI patients at Cho Ray Hospital between January 2020 and September 2021. All participants were identified for ACE I/D polymorphism using the polymerase chain reaction method, with follow-up on survival status at 12 months from the date of admission. The proportions of II, ID, and DD genotypes of the ACE I/D variant were 49.5%, 35.9%, and 14.6%, respectively. All-cause mortality after 12 months occurred in 58 cases (10.6%). The ACE I/D polymorphism did not affect all-cause mortality in the dominant (P = .196), recessive (P = .827), homozygous (P = .515), and heterozygous (P = .184) models. A subgroup analysis by usage status of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) showed that in the non-ACEI/ARB group, patients with the DD genotype had a lower cumulative survival probability than patients with the II/ID genotypes (hazard ratio [HR] = 3.97, 95% confidence interval [CI]: 1.21-13.04; P = .023). Among patients with Global Registry of Acute Coronary Events (GRACE) scores below the median (153.5 points), those with DD genotype had a higher risk of mortality than those with the II/ID genotypes (HR = 3.35, 95% CI: 1.01-11.11; P = .049). The ACE I/D genetic polymorphism was found not to be associated with 12-month all-cause mortality in Vietnamese patients with AMI. However, it was associated with mortality in patients who did not use ACEI/ARB and also whose GRACE scores were below 153.5 points., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2023
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16. Association between ACE I/D genetic polymorphism and the severity of coronary artery disease in Vietnamese patients with acute myocardial infarction.
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Tran DC, Le LHG, Thai TT, Hoang SV, Do MD, and Truong BQ
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Background: The severity of coronary artery disease is a prognostic factor for major adverse cardiovascular events in patients diagnosed with acute myocardial infarction. ACE I/D polymorphism is one of the genetic factors that may affect the severity of coronary artery disease. This study aimed to investigate the association between ACE I/D genotypes and the severity of coronary artery disease in patients with acute myocardial infarction., Materials and Methods: A single-center, prospective, observational study was conducted at the Department of Cardiology and Department of Interventional Cardiology, Cho Ray Hospital, Ho Chi Minh City, Vietnam from January 2020 to June 2021. All participants diagnosed with acute myocardial infarction underwent contrast-enhanced coronary angiography. The severity of coronary artery disease was determined by Gensini score. ACE I/D genotypes were identified in all subjects by using the polymerase chain reaction method., Results: A total of 522 patients diagnosed with first acute myocardial infarction were recruited. The patients' median Gensini score was 34.3. The II, ID, and DD genotype rates of ACE I/D polymorphism were 48.9%, 36.4%, and 14.7%, respectively. After adjusting for confounding factors, multivariable linear regression analysis showed that the ACE DD genotype was independently associated with a higher Gensini score compared with the II or ID genotypes., Conclusion: The DD genotype of the ACE I/D polymorphism was associated with the severity of coronary artery disease in Vietnamese patients diagnosed with first acute myocardial infarction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Tran, Le, Thai, Hoang, Do and Truong.)
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- 2023
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17. Prevalence of Thalassemia in the Vietnamese Population and Building a Clinical Decision Support System for Prenatal Screening for Thalassemia.
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Tran DC, Dang AL, Hoang TNL, Nguyen CT, Le TMP, Dinh TNM, Tran VA, Doan TKP, and Nguyen TT
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Introduction: The prevalence of thalassemia among the Vietnamese population was studied, and clinical decision support systems for prenatal screening of thalassemia were created. The aim of this report was to investigate the prevalence of thalassemia in the Vietnamese population, building a clinical decision support system for prenatal screening for thalassemia., Methods: A cross-sectional study was conducted on pregnant women and their husbands visiting the Vietnam National Hospital of Obstetrics and Gynecology from October 2020 to December 2021. A total of 10112 medical records of first-time pregnant women and their husbands were collected., Results: A clinical decision support system was built, including 2 different types of systems for prenatal screening for thalassemia (an expert system and 4 AI-based CDSS). One thousand nine hundred ninety-two cases were used to train and test machine learning models, while 1555 cases were used for specialized expert system evaluation. There were ten key variables for AI-based CDSS for machine learning. The four most important features in thalassemia screening were identified. The accuracy of the expert system and AI-based CDSS was compared. The rate of patients with Alpha thalassemia is 10.73% (1085 patients), the rate of patients with beta-thalassemia is 2.24% (227 patients), and 0.29% (29 patients) of patients carry both alpha-thalassemia and beta-thalassemia gene mutations. The expert system showed an accuracy of 98.45%. Among the AI-based CDSS developed, the multilayer perceptron (MLP) model was the most stable regardless of the training database (accuracy of 98,5% using all features and 97% using only the four most important features)., Conclusions: When comparing the expert system with the AI-based CDSS, the accuracy of the expert system and AI-based models was comparable. The developed expert system for prenatal thalassemia screening showed high accuracy. AI-based CDSS showed satisfactory results. Further development of such systems is promising with a view to their introduction into clinical practice., Competing Interests: Competing interests: The authors declare no conflict of Interest.
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- 2023
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18. Bictegravir-Induced Drug Reaction With Eosinophilia and Systemic Symptoms in a Patient With Acute Human Immunodeficiency Virus.
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DiLorenzo MA, Medrano N, Chen JN, Bawany F, Tran DC, Taunk P, Meehan SA, Pomeranz MK, and Mgbako O
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Although drug reaction with eosinophilia and systemic symptoms (DRESS) is associated with antiretrovirals, there are no published reports of bictegravir-induced DRESS. Bictegravir is recommended as first-line treatment for patients with human immunodeficiency virus (HIV). Recognition of DRESS, its skin manifestations, and potential complications is vital for appropriate care and management of acute HIV., Competing Interests: Potential conflicts of interest. MAD holds individual stocks in Abbvie, Abiomed Inc., Amgen Inc, Becton Dickinson, BioMarin Pharmaceutical Inc., Bristol-Myers Squibb, CVS Health Corporation, Gilead Sciences, Inc., Henry Schein, Inc., Hologic, Jazz Pharmaceuticals, Merck & Co., Inc., Quest Diagnostics, Vertex Pharmaceuticals, and West Pharmaceuticals. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2023
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19. Mohs micrographic surgery reduces the need for a repeat surgery for primary Merkel cell carcinoma when compared to wide local excision: A retrospective cohort study of a commercial insurance claims database.
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Tran DC, Ovits C, Wong P, and Kim RH
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Competing Interests: None disclosed.
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- 2022
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20. Delayed-onset psoriasiform eruption secondary to a phosphoinositide 3-kinase inhibitor: A case report and literature review.
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Tran DC, Karim M, Lo Sicco K, Brinster N, Milam EC, and Tattersall IW
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Competing Interests: Dr Lo Sicco is an investigator for Regen Lab and Pfizer and a recipient of an educational grant from Pfizer. Dr Milam received honorarium from the National Eczema Association for assistance with creation of educational material. Dr Tran, Author Karim, Drs Tattersall and Brinster have no conflicts of interest to declare.
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- 2022
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21. HLA class I allele-lacking leukocytes predict rare clonal evolution to MDS/AML in patients with acquired aplastic anemia.
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Hosokawa K, Mizumaki H, Yoroidaka T, Maruyama H, Imi T, Tsuji N, Urushihara R, Tanabe M, Zaimoku Y, Nguyen MAT, Tran DC, Ishiyama K, Yamazaki H, Katagiri T, Takamatsu H, Hosomichi K, Tajima A, Azuma F, Ogawa S, and Nakao S
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- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Clonal Evolution genetics, Female, Humans, Male, Middle Aged, Retrospective Studies, Clonal Evolution immunology, HLA-A Antigens genetics, HLA-A Antigens immunology, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute immunology, Leukocytes immunology, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes immunology
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- 2021
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22. State-of-the-art IoV trust management a meta-synthesis systematic literature review (SLR).
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Rehman A, Hassan MF, Yew KH, Paputungan I, and Tran DC
- Abstract
In the near future, the Internet of Vehicles (IoV) is foreseen to become an inviolable part of smart cities. The integration of vehicular ad hoc networks (VANETs) into the IoV is being driven by the advent of the Internet of Things (IoT) and high-speed communication. However, both the technological and non-technical elements of IoV need to be standardized prior to deployment on the road. This study focuses on trust management (TM) in the IoV/VANETs/ITS (intelligent transport system). Trust has always been important in vehicular networks to ensure safety. A variety of techniques for TM and evaluation have been proposed over the years, yet few comprehensive studies that lay the foundation for the development of a "standard" for TM in IoV have been reported. The motivation behind this study is to examine all the TM models available for vehicular networks to bring together all the techniques from previous studies in this review. The study was carried out using a systematic method in which 31 papers out of 256 research publications were screened. An in-depth analysis of all the TM models was conducted and the strengths and weaknesses of each are highlighted. Considering that solutions based on AI are necessary to meet the requirements of a smart city, our second objective is to analyze the implications of incorporating an AI method based on "context awareness" in a vehicular network. It is evident from mobile ad hoc networks (MANETs) that there is potential for context awareness in ad hoc networks. The findings are expected to contribute significantly to the future formulation of IoVITS standards. In addition, gray areas and open questions for new research dimensions are highlighted., Competing Interests: The authors declare that they have no competing interests., (© 2020 Rehman et al.)
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- 2020
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23. Treatment of Multi-Focal Epilepsy With Resective Surgery Plus Responsive Neurostimulation (RNS): One Institution's Experience.
- Author
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Tran DK, Tran DC, Mnatsakayan L, Lin J, Hsu F, and Vadera S
- Abstract
Objective: Patients with medically refractory focal epilepsy can be difficult to treat surgically, especially if invasive monitoring reveals multiple ictal onset zones. Possible therapeutic options may include resection, neurostimulation, laser ablation, or a combination of these surgical modalities. To date, no study has examined outcomes associated with resection plus responsive neurostimulation (RNS, Neuropace, Inc., Mountain View, CA) implantation and we describe our initial experience in patients with multifocal epilepsy undergoing this combination therapy. Methods: A total of 43 responsive neurostimulation (RNS) devices were implanted at UCI from 2015 to 2019. We retrospectively reviewed charts of patients from the same time period who underwent both resection and RNS implantation. Patients were required to have independent or multifocal onset, undergo resection and RNS implantation, and have a minimum of six-months for follow-up to be included in the study. Demographics, location of ictal onset, location of surgery, complications, and seizure outcome were collected. Results: Ten patients met inclusion criteria for the study, and seven underwent both procedures in the same setting. The average age was 36. All patients had multifocal ictal onset on video electroencephalogram or invasive EEG with four patients undergoing subdural grid placement and four patients undergoing bilateral sEEG prior to the definitive surgery. Five patients underwent resection plus ipsilateral RNS placement and the remainder underwent resection with contralateral RNS placement. Two minor complications were encountered in this group. At six months follow up, there was an average of 81% ± 9 reduction in seizures, while four patients experienced complete seizure freedom at 1 year. Conclusion: Patients with multifocal epilepsy can be treated with partial resection plus RNS. The complication rates are low with potential for worthwhile seizure reduction., (Copyright © 2020 Tran, Tran, Mnatsakayan, Lin, Hsu and Vadera.)
- Published
- 2020
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24. Embedding Amorphous Molybdenum Sulfide within a Porous Poly(3,4-ethylenedioxythiophene) Matrix to Enhance its H 2 -evolving Catalytic Activity and Robustness.
- Author
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Nguyen AD, Pham PT, Tran DC, Nguyen LT, and Tran PD
- Abstract
Amorphous molybdenum sulfide (MoS
x ) is a promising alternative to Pt catalyst for the H2 evolution in water. However, it is suffered of an electrochemical corrosion. In this report, we present a strategy to tack this issue by embedding the MoSx catalyst within a porous poly(3,4-ethylenedioxythiophene) (PEDOT) matrix. The PEDOT host is firstly grown onto a fluorine-doped tin oxide (FTO) electrode by electrochemical polymerization of EDOT monomer in an acetonitrile solution to perform a porous structure. The MoSx catalyst is subsequently deposited onto the PEDOT by an electrochemical oxidation of [MoS4 ]2- monomer. In a 0.5 M H2 SO4 electrolyte solution, the MoSx /PEDOT shows higher H2 -evolving catalytic activities (current density of 34.2 mA/cm2 at -0.4 V vs RHE) in comparison to a pristine MoSx grown on a planar FTO electrode having similar catalyst loading (24.2 mA/cm2 ). The PEDOT matrix contributes to enhance the stability of MoSx catalyst by a significant manner. As such, the MoSx /PEDOT retains 81 % of its best catalytic activity after 1000 potential scans from 0 to -0.4 V vs. RHE, whereas a planar MoSx catalyst is completely degraded after about 240 potential scans, due to its complete corrosion., (© 2020 Wiley-VCH GmbH.)- Published
- 2020
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25. The First Vietnamese FOSD-Tacotron-2-based Text-to-Speech Model Dataset.
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Tran DC
- Abstract
Recent trends in voicebot application development have enabled utilization of both speech-to-text and text-to-speech (TTS) generation techniques. In order to generate a voice response to a given speech, one needs to use a TTS engine. The recently developed TTS engines are shifting towards end-to-end approaches utilizing models such as Tacotron, Tacotron-2, WaveNet, and WaveGlow. The reason is that it enables a TTS service provider to focus on developing training and validating datasets comprising of labelled texts and recorded speeches instead of designing an entirely new model that outperforms the others which is time-consuming and costly. In this context, this work introduces the first Vietnamese FPT Open Speech Data (FOSD)-Tacotron-2-based TTS model dataset. This dataset comprises of a configuration file in *.json format; training and validating text input files (in *.csv format); a 225,000-step checkpoint of the trained model; and several sample generated audios. The published dataset is extremely worth for serving as a model for benchmarking with other newly developed TTS models / engines. In addition, it opens an entirely new TTS research optimization problem to be addressed: How to effectively generate speech from text given: a black box TTS (trained) model and its training and validation input texts., Competing Interests: Copyright 2018 FPT Corporation Permission is hereby granted, free of charge, non-exclusive, worldwide, irrevocable, to any person obtaining a copy of this data or software and associated documentation files (the “Data or Software”), to deal in the Data or Software without restriction, including without limitation the rights to use, copy, modify, remix, transform, merge, build upon, publish, distribute and redistribute, sublicense, and/or sell copies of the Data or Software, for any purpose, even commercially, and to permit persons to whom the Data or Software is furnished to do so, subject to the following conditions: The above copyright notice, and this permission notice, and indication of any modification to the Data or Software, shall be included in all copies or substantial portions of the Data or Software. THE DATA OR SOFTWARE IS PROVIDED “AS IS”, WITHOUT WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION WITH THE DATA OR SOFTWARE OR THE USE OR OTHER DEALINGS IN THE DATA OR SOFTWARE. Patent and trademark rights are not licensed under this FPT Public License., (© 2020 The Author(s).)
- Published
- 2020
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26. Pembrolizumab for advanced basal cell carcinoma: An investigator-initiated, proof-of-concept study.
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Chang ALS, Tran DC, Cannon JGD, Li S, Jeng M, Patel R, Van der Bokke L, Pague A, Brotherton R, Rieger KE, Satpathy AT, Yost KE, Reddy S, Sarin K, and Colevas AD
- Subjects
- Antineoplastic Agents, Immunological therapeutic use, Carcinoma, Basal Cell pathology, Disease-Free Survival, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Infusions, Intravenous, Male, Neoplasm Invasiveness pathology, Neoplasm Staging, Prognosis, Prospective Studies, Risk Assessment, Skin Neoplasms pathology, Survival Analysis, Treatment Outcome, Anilides therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Carcinoma, Basal Cell drug therapy, Carcinoma, Basal Cell mortality, Pyridines therapeutic use, Skin Neoplasms drug therapy, Skin Neoplasms mortality
- Published
- 2019
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27. Reply to: "Use of immortal time within survival analysis".
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Min Lee CK, Li S, Tran DC, Zhu GA, Kim J, Kwong BY, and Chang ALS
- Subjects
- Time Factors, Survival Analysis
- Published
- 2019
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28. Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: A retrospective case-control study.
- Author
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Min Lee CK, Li S, Tran DC, Zhu GA, Kim J, Kwong BY, and Chang ALS
- Subjects
- Adult, Aged, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Agents, Immunological therapeutic use, Case-Control Studies, Disease-Free Survival, Female, Humans, Kaplan-Meier Estimate, Lichenoid Eruptions chemically induced, Male, Middle Aged, Neoplasms mortality, Nivolumab therapeutic use, Retrospective Studies, Treatment Outcome, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal, Humanized adverse effects, Antineoplastic Agents, Immunological adverse effects, B7-H1 Antigen antagonists & inhibitors, Drug Eruptions etiology, Neoplasm Proteins antagonists & inhibitors, Neoplasms drug therapy, Nivolumab adverse effects, Programmed Cell Death 1 Receptor antagonists & inhibitors
- Abstract
Background: Cutaneous adverse events are common with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors. However, the nature of the specific cutaneous adverse event of dermatitis has not been investigated across various PD-1/PD-L1 inhibitors. Oncologic outcomes potentially associated with dermatitis are not well characterized., Objective: To assess the nature of dermatitis after exposure to a PD-1/PD-L1 inhibitor and oncologic outcomes associated with dermatitis., Methods: Retrospective, matched, case-control study conducted at a single academic center., Results: The most common histologic patterns were lichenoid dermatitis (50%) and spongiotic dermatitis (40%). The overall tumor response rate was 65.0% for the case patients and 17.0% for the controls (P = .0007) (odds ratio, 7.3; 95% confidence interval, 2.3-23.1). The progression-free survival and overall survival times were significantly longer for the case patients than for the controls by Kaplan-Meier analysis (P < .0001 and .0203, respectively)., Limitations: The retrospective design and relatively small sample size precluded matching for all cancer types., Conclusions: Lichenoid and spongiotic dermatitis associated with PD-1/PD-L1 inhibitors could be a sign of robust immune response and improved oncologic outcomes. The value of PD-1/PD-L1-related dermatitis in predicting cancer outcomes awaits investigation through prospective multicenter studies for specific cancer types., (Copyright © 2018. Published by Elsevier Inc.)
- Published
- 2018
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29. Cell-Based Therapies in Vascularized Composite Allotransplantation.
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Vyas KS, Mohan AT, Morrison SD, Tran DC, and Mardini S
- Subjects
- Animals, Dendritic Cells immunology, Humans, Immunosuppression Therapy, Models, Animal, Rats, Cell Proliferation physiology, Cell- and Tissue-Based Therapy methods, Dendritic Cells transplantation, Graft Survival physiology, Vascularized Composite Allotransplantation
- Abstract
Background: Dendritic cells (DCs) are bone marrow-derived, professional antigen-presenting cells with tolerogenic function. The ability of DCs to regulate alloantigen-specific T cell responses and to promote tolerance has aligned them ideally for a role in vascularized composite allotransplantation (VCA). In this study, we summarize the current evidence for DC therapies for tolerance induction to alleviate the requirement for chronic immunosuppression., Method: A comprehensive and structured review of manuscripts published on VCA was performed using the MEDLINE and PubMed databases. All eligible studies published from the year 2000 to 2017 were included in the final results., Result: Nineteen original preclinical and clinical studies that employed cell therapy for VCA were included in this review. In vivo DC therapy was found to direct the alloimmune response toward either transplant rejection or tolerance in VCA models. While injection of mature DCs rapidly increases T-cell activity in humans and promotes transplant rejection, the injection of immature DCs acts as an immunosuppressant and inhibits T-cell activity. In addition to immature DCs, mesenchymal stem cells were also found to have a positive effect on allotransplantation of solid organs and bone marrow via cytokine expression which decreases the alloreactive effector lymphocytes and increases CD4+/CD25+/FoxP3 Tregs. Despite the promising findings, the efficacy of cell-based therapies varies greatly across studies, partly due to different methods of cell isolation and purification techniques, source, route and timing of administration, and combination immunosuppressive therapy., Conclusion: Additional research is needed to evaluate the efficacy and safety of DC and other cell-based therapeutic measures in human allotransplant recipients. Future direction will focus on the development of novel methods to reduce immunosuppression and develop more individualized management, as well as the clinical application of basic research in the mechanisms of immunologic tolerance., Competing Interests: There are no commercial or financial relationships that could be construed as a potential conflict of interest., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)
- Published
- 2018
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30. How and why studies disagree about the effects of education on health: A systematic review and meta-analysis of studies of compulsory schooling laws.
- Author
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Hamad R, Elser H, Tran DC, Rehkopf DH, and Goodman SN
- Subjects
- Global Health, Humans, Education legislation & jurisprudence, Educational Status, Health Status
- Abstract
Rich literatures across multiple disciplines document the association between increased educational attainment and improved health. While quasi-experimental studies have exploited variation in educational policies to more rigorously estimate the health effects of education, there remains disagreement about whether education and health are causally linked. The aim of this study was to conduct a systematic review and meta-analysis to characterize this literature, with a focus on quasi-experimental studies of compulsory schooling laws (CSLs). Articles from 1990 to 2015 were obtained through electronic searches and manual searches of reference lists. We searched for English-language studies and included manuscripts if: (1) they involved original data analysis; (2) outcomes were health-related; and (3) the primary predictor utilized variation in CSLs. We identified 89 articles in 25 countries examining over 25 health outcomes, with over 600 individual point estimates. We systematically characterized heterogeneity on key study design features and conducted a meta-analysis of studies with comparable health outcome and exposure variables. Within countries, studies differed in terms of birth cohorts included, the measurement of health outcomes within a given category, and the type of CSL variation examined. Over 90% of manuscripts included multiple analytic techniques, such as econometric and standard regression methods, with as many as 31 "primary" models in a single study. A qualitative synthesis of study findings indicated that educational attainment has an effect on the majority of health outcomes-most beneficial, some negative-while the meta-analysis demonstrated small beneficial effects for mortality, smoking, and obesity. Future work could focus on inconsistent findings identified by this study, or review the health effects of other types of educational policies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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31. Levocarnitine for vismodegib-associated muscle spasms: a pilot randomized, double-blind, placebo-controlled, investigator-initiated trial.
- Author
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Cannon JGD, Tran DC, Li S, and Chang AS
- Subjects
- Aged, Double-Blind Method, Female, Humans, Male, Middle Aged, Pilot Projects, Spasm chemically induced, Anilides adverse effects, Antineoplastic Agents adverse effects, Carcinoma, Basal Cell drug therapy, Carnitine therapeutic use, Pyridines adverse effects, Skin Neoplasms drug therapy, Spasm drug therapy
- Published
- 2018
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32. An exploratory open-label, investigator-initiated study to evaluate the efficacy and safety of combination sonidegib and buparlisib for advanced basal cell carcinomas.
- Author
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Tran DC, Moffat A, Brotherton R, Pague A, Zhu GA, and Chang ALS
- Subjects
- Aged, Aged, 80 and over, Aminopyridines adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biphenyl Compounds adverse effects, Carcinoma, Basal Cell mortality, Cohort Studies, Disease-Free Survival, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Male, Maximum Tolerated Dose, Middle Aged, Morpholines adverse effects, Neoplasm Invasiveness pathology, Neoplasm Staging, Prognosis, Prospective Studies, Pyridines adverse effects, Skin Neoplasms mortality, Survival Analysis, Treatment Outcome, Aminopyridines administration & dosage, Biphenyl Compounds administration & dosage, Carcinoma, Basal Cell drug therapy, Carcinoma, Basal Cell pathology, Morpholines administration & dosage, Pyridines administration & dosage, Skin Neoplasms drug therapy, Skin Neoplasms pathology
- Published
- 2018
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33. An 18-year retrospective study on the outcomes of keratoacanthomas with different treatment modalities at a single academic centre.
- Author
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Tran DC, Li S, Henry S, Wood DJ, and Chang ALS
- Subjects
- Aged, Chronic Disease, Follow-Up Studies, Humans, Recurrence, Retrospective Studies, Treatment Outcome, Watchful Waiting, Keratoacanthoma therapy
- Published
- 2017
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34. Initial in vitro functional characterization of serum exosomal microRNAs from patients with metastatic basal cell carcinoma.
- Author
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Chang J, Tran DC, Zhu GA, Li R, Whitson R, Kim YH, Gupta A, Afshari A, Antes T, Spitale RC, and Chang ALS
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor metabolism, Exosomes metabolism, Female, Humans, Male, Middle Aged, Neoplasm Metastasis, Pilot Projects, Carcinoma, Basal Cell pathology, Exosomes physiology, MicroRNAs metabolism, Skin Neoplasms pathology
- Published
- 2017
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35. A Systematic Review of the Use of Telemedicine in Plastic and Reconstructive Surgery and Dermatology.
- Author
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Vyas KS, Hambrick HR, Shakir A, Morrison SD, Tran DC, Pearson K, Vasconez HC, Mardini S, Gosman AA, Dobke M, and Granick MS
- Subjects
- Humans, Dermatology, Plastic Surgery Procedures, Surgery, Plastic, Telemedicine
- Abstract
Background: Telemedicine, the use of information technology and telecommunication to provide healthcare at a distance, is a burgeoning field with applications throughout medicine. Given the visual nature of plastic surgery and dermatology, telemedicine has a myriad of potential applications within the field., Methods: A comprehensive literature review of articles published on telemedicine since January 2010 was performed. Articles were selected for their relevance to plastic and reconstructive surgery and dermatology, and then reviewed for their discussion of the applications, benefits, and limitations of telemedicine in practice., Results: A total of 3119 articles were identified in the initial query. Twenty-three articles met the inclusion criteria in plastic surgery (7 wound management, 5 burn management, 5 trauma, 4 free flap care, 2 in cleft lip/palate repair). Twenty-three (100%) reported a benefit of telemedicine often related to improved postoperative monitoring, increased access to expertise in rural settings, and cost savings, either predicted or actualized. Eight (35%) reported limitations and barriers to the application of telemedicine, including overdiagnosis and dependence on functional telecommunication systems. Sixty-six articles focused on telemedicine in dermatology and also demonstrated significant promise., Conclusions: Telemedicine holds special promise in increasing the efficiency of postoperative care for microsurgical procedures, improving care coordination and management of burn wounds, facilitating interprofessional collaboration across time and space, eliminating a significant number of unnecessary referrals, and connecting patients located far from major medical centers with professional expertise without impinging on-and in some cases improving-the quality or accuracy of care provided. Teledermatology consultation was found to be safe and has a comparable or superior efficacy to the traditional in-patient consultation. The system was consistently rated as convenient and easy to use by patients, referring physicians, and consulting dermatologists. Teledermatology has also been used as an educational tool for patients. A significant number of studies detailed strategies to improve the current state of teledermatology, either by implementing new programs or improving technologies. Telemedicine use is widespread among plastic surgeons and is enabling the spread of expertise beyond major medical centers. Further research is needed to conclusively demonstrate benefit in routine clinical care.
- Published
- 2017
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36. Synthesis and Bioactivity Evaluation of Novel 2-Salicyloylbenzofurans as Antibacterial Agents.
- Author
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Phan PT, Nguyen TT, Nguyen HT, Le BN, Vu TT, Tran DC, and Pham TN
- Subjects
- Anti-Bacterial Agents pharmacology, Benzofurans pharmacology, Enterococcus faecalis drug effects, Escherichia coli drug effects, Methicillin-Resistant Staphylococcus aureus drug effects, Microbial Sensitivity Tests, Salicylates pharmacology, Anti-Bacterial Agents chemical synthesis, Benzofurans chemical synthesis, Salicylates chemical synthesis
- Abstract
In order to discover new antibacterial agents, series of 2-salicyloylbenzofuran derivatives were designed, synthesized and evaluated for their antibacterial activities against three Gram-(+) strains (methicillin-sensitive Staphylococcus aureus (MSSA) ATCC 29213, methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, and Streptococcus faecalis ( S. faecalis ) ATCC 29212) and one Gram-(-) strain ( Escherichia coli (E. coli) ATCC 25922). The 2-salicyloylbenzofuran heterocycles were generated by Rap-Stoermer condensation of salicylaldehydes with phenacyl bromides and then converted to diverse O -ether derivatives by Williamson synthesis. The targeted products were screened for in vitro qualitative (zone of inhibition) and quantitative (MIC) antibacterial activities by agar well diffusion assay and agar dilution method. Amongst the compounds, those bearing carboxylic acid functional group were found to exhibit reasonable activity against Gram-(+) bacterial strains including S. faecalis , MSSA and MRSA with the most potent antibacterial agent 8h (MICs = 0.06-0.12 mM). Besides, the 2-salicyloylbenzofurans partly displayed inhibitory activity against MRSA with the best MICs = 0.14 mM ( 8f ) and 0.12 mM ( 8h ). Finally, the antibacterial results preliminarily suggested that the substituent bearing carboxylic acid group at salicyloyl-C2 and the bromine atoms on the benzofuran moiety seem to be the functionality necessary for antibacterial activities.
- Published
- 2017
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37. Follow-up on Programmed Cell Death 1 Inhibitor for Cutaneous Squamous Cell Carcinoma.
- Author
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Tran DC, Colevas AD, and Chang AL
- Subjects
- Aged, Antineoplastic Agents, Immunological therapeutic use, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Cell Death, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Nivolumab, Skin Neoplasms metabolism, Time Factors, Treatment Outcome, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Carcinoma, Squamous Cell drug therapy, Programmed Cell Death 1 Receptor antagonists & inhibitors, Skin Neoplasms drug therapy, Skin Neoplasms pathology
- Published
- 2017
- Full Text
- View/download PDF
38. Navigating sticky areas in transdermal product development.
- Author
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Strasinger C, Raney SG, Tran DC, Ghosh P, Newman B, Bashaw ED, Ghosh T, and Shukla CG
- Subjects
- Administration, Cutaneous, Animals, Humans, Skin metabolism, Drug Delivery Systems, Pharmaceutical Preparations administration & dosage
- Abstract
The benefits of transdermal delivery over the oral route to combat such issues of low bioavailability and limited controlled release opportunities are well known and have been previously discussed by many in the field (Prausnitz et al. (2004) [1]; Hadgraft and Lane (2006) [2]). However, significant challenges faced by developers as a product moves from the purely theoretical to commercial production have hampered full capitalization of the dosage forms vast benefits. While different technical aspects of transdermal system development have been discussed at various industry meetings and scientific workshops, uncertainties have persisted regarding the pharmaceutical industry's conventionally accepted approach for the development and manufacturing of transdermal systems. This review provides an overview of the challenges frequently faced and the industry's best practices for assuring the quality and performance of transdermal delivery systems and topical patches (collectively, TDS). The topics discussed are broadly divided into the evaluation of product quality and the evaluation of product performance; with the overall goal of the discussion to improve, advance and accelerate commercial development in the area of this complex controlled release dosage form., (Published by Elsevier B.V.)
- Published
- 2016
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39. The Shelterin TIN2 Subunit Mediates Recruitment of Telomerase to Telomeres.
- Author
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Frank AK, Tran DC, Qu RW, Stohr BA, Segal DJ, and Xu L
- Subjects
- Aminopeptidases metabolism, Cell Line, Tumor, DNA Repair genetics, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases metabolism, Dyskeratosis Congenita genetics, Gene Knock-In Techniques, HCT116 Cells, Humans, Mutation genetics, Serine Proteases metabolism, Shelterin Complex, Telomere Homeostasis genetics, Telomeric Repeat Binding Protein 1 genetics, Tripeptidyl-Peptidase 1, Telomerase metabolism, Telomere metabolism, Telomere Shortening genetics, Telomere-Binding Proteins genetics
- Abstract
Dyskeratosis Congenita (DC) is a heritable multi-system disorder caused by abnormally short telomeres. Clinically diagnosed by the mucocutaneous symptoms, DC patients are at high risk for bone marrow failure, pulmonary fibrosis, and multiple types of cancers. We have recapitulated the most common DC-causing mutation in the shelterin component TIN2 by introducing a TIN2-R282H mutation into cultured telomerase-positive human cells via a knock-in approach. The resulting heterozygous TIN2-R282H mutation does not perturb occupancy of other shelterin components on telomeres, result in activation of telomeric DNA damage signaling or exhibit other characteristics indicative of a telomere deprotection defect. Using a novel assay that monitors the frequency and extension rate of telomerase activity at individual telomeres, we show instead that telomerase elongates telomeres at a reduced frequency in TIN2-R282H heterozygous cells; this recruitment defect is further corroborated by examining the effect of this mutation on telomerase-telomere co-localization. These observations suggest a direct role for TIN2 in mediating telomere length through telomerase, separable from its role in telomere protection.
- Published
- 2015
- Full Text
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40. Maximal Usage Trial: An Overview of the Design of Systemic Bioavailability Trial for Topical Dermatological Products.
- Author
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Bashaw ED, Tran DC, Shukla CG, and Liu X
- Abstract
Dermatologic diseases can present in varying forms and severity, ranging from the individual lesion and up to almost total skin involvement. Pharmacokinetic assessment of topical drug products has previously been plagued by bioanalytical assay limitations and the lack of a standardized study design. Since the mid-1990's the US Food and Drug Administration has developed and implemented a pharmacokinetic maximal usage trial (MUsT) design to help address these issues. The MUsT design takes into account the following elements: the enrollment of patients rather than normal volunteers, the frequency of dosing, duration of dosing, use of highest proposed strength, total involved surface area to be treated at one time, amount applied per square centimeter, application method and site preparation, product formulation, and use of a sensitive bioanalytical method that has been properly validated. This paper provides a perspective of pre-MUsT study designs and a discussion of the individual elements that make up a MUsT.
- Published
- 2015
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41. Combinatorial H3K9acS10ph histone modification in IgH locus S regions targets 14-3-3 adaptors and AID to specify antibody class-switch DNA recombination.
- Author
-
Li G, White CA, Lam T, Pone EJ, Tran DC, Hayama KL, Zan H, Xu Z, and Casali P
- Subjects
- 14-3-3 Proteins genetics, Animals, Cytidine Deaminase immunology, DNA immunology, Histones immunology, Immunoglobulin Heavy Chains immunology, Immunoglobulin Variable Region genetics, Mice, Mice, Inbred C57BL, Models, Molecular, Recombination, Genetic, 14-3-3 Proteins metabolism, Cytidine Deaminase genetics, DNA genetics, Histones genetics, Immunoglobulin Class Switching genetics, Immunoglobulin Heavy Chains genetics
- Abstract
Class-switch DNA recombination (CSR) is central to the antibody response, in that it changes the immunoglobulin heavy chain (IgH) constant region, thereby diversifying biological effector functions of antibodies. The activation-induced cytidine deaminase (AID)-centered CSR machinery excises and rejoins DNA between an upstream (donor) and a downstream (acceptor) S region, which precede the respective constant region DNA. AID is stabilized on S regions by 14-3-3 adaptors. These adaptors display a high affinity for 5'-AGCT-3' repeats, which recur in all S regions. However, how 14-3-3, AID, and the CSR machinery target exclusively the donor and acceptor S regions is poorly understood. Here, we show that histone methyltransferases and acetyltransferases are induced by CD40 or Toll-like receptor signaling and catalyze H3K4me3 and H3K9ac/K14ac histone modifications, which are enriched in S regions but do not specify the S region targets of CSR. By contrast, the combinatorial H3K9acS10ph modification specifically marks the S regions set to recombine and directly recruits 14-3-3 adaptors for AID stabilization there. Inhibition of the enzymatic activity of GCN5 and PCAF histone acetyltransferases reduces H3K9acS10ph in S regions, 14-3-3 and AID stabilization, and CSR. Thus, H3K9acS10ph is a histone code that is "written" specifically in S regions and is "read" by 14-3-3 adaptors to target AID for CSR as an important biological outcome., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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42. Iron inhibits activation-induced cytidine deaminase enzymatic activity and modulates immunoglobulin class switch DNA recombination.
- Author
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Li G, Pone EJ, Tran DC, Patel PJ, Dao L, Xu Z, and Casali P
- Subjects
- Animals, Cell Differentiation physiology, Cytidine Deaminase genetics, Immunoglobulin A genetics, Immunoglobulin A metabolism, Immunoglobulin G genetics, Immunoglobulin G metabolism, Mice, Plasma Cells cytology, Cytidine Deaminase antagonists & inhibitors, Cytidine Deaminase metabolism, DNA Breaks, Double-Stranded, Immunoglobulin Class Switching physiology, Iron metabolism, Plasma Cells metabolism, Recombination, Genetic physiology
- Abstract
Immunoglobulin (Ig) class switch DNA recombination (CSR) and somatic hypermutation (SHM) are critical for the maturation of the antibody response. Activation-induced cytidine deaminase (AID) initiates CSR and SHM by deaminating deoxycytidines (dCs) in switch (S) and V(D)J region DNA, respectively, to generate deoxyuracils (dUs). Processing of dUs by uracil DNA glycosylase (UNG) yields abasic sites, which are excised by apurinic/apyrimidinic endonucleases, eventually generating double strand DNA breaks, the obligatory intermediates of CSR. Here, we found that the bivalent iron ion (Fe(2+), ferrous) suppressed CSR, leading to decreased number of switched B cells, decreased postrecombination Iμ-C(H) transcripts, and reduced titers of secreted class-switched IgG1, IgG3, and IgA antibodies, without alterations in critical CSR factors, such as AID, 14-3-3γ, or PTIP, or in general germline I(H)-S-C(H) transcription. Fe(2+) did not affect B cell proliferation or plasmacytoid differentiation. Rather, it inhibited AID-mediated dC deamination in a dose-dependent fashion. The inhibition of intrinsic AID enzymatic activity by Fe(2+) was specific, as shown by lack of inhibition of AID-mediated dC deamination by other bivalent metal ions, such as Zn(2+), Mn(2+), Mg(2+), or Ni(2+), and the inability of Fe(2+) to inhibit UNG-mediated dU excision. Overall, our findings have outlined a novel role of iron in modulating a B cell differentiation process that is critical to the generation of effective antibody responses to microbial pathogens and tumoral cells. They also suggest a possible role of iron in dampening AID-dependent autoimmunity and neoplastic transformation.
- Published
- 2012
- Full Text
- View/download PDF
43. Clinical pharmacology aspects of sex-related drug products.
- Author
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Tran DC, Apparaju S, Yu C, Lee L, Kim H, and Kim MJ
- Subjects
- Drug Labeling trends, Drugs, Investigational adverse effects, Female, Humans, Male, United States, United States Food and Drug Administration, Drug Approval, Drugs, Investigational pharmacokinetics, Drugs, Investigational pharmacology, Sexual Dysfunction, Physiological drug therapy
- Abstract
Clinical pharmacology plays an important role in drug development, including evaluation of a drug's pharmacokinetics (PK), interaction potential, exposure-response relationship, and pharmacogenomics (Table 1). Reviewers in the Office of Clinical Pharmacology at the US Food and Drug Administration (FDA) consider these issues to facilitate drug development and to ensure that drug products are safe and effective. This article highlights some of the important clinical pharmacology topics in the development of sex-related drug products.
- Published
- 2011
- Full Text
- View/download PDF
44. Pharmacokinetics of 1,4-butanediol in rats: bioactivation to gamma-hydroxybutyric acid, interaction with ethanol, and oral bioavailability.
- Author
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Fung HL, Tsou PS, Bulitta JB, Tran DC, Page NA, Soda D, and Mi Fung S
- Subjects
- Administration, Oral, Animals, Biological Availability, Butylene Glycols blood, Dose-Response Relationship, Drug, Drug Interactions physiology, Male, Rats, Rats, Sprague-Dawley, Sodium Oxybate metabolism, Butylene Glycols administration & dosage, Butylene Glycols pharmacokinetics, Ethanol pharmacokinetics, Sodium Oxybate blood
- Abstract
1,4-Butanediol (BD), a substance of abuse, is bioactivated to gamma-hydroxybutyrate (GHB), but its fundamental pharmacokinetics (PK) have not been characterized. Because this bioactivation is partly mediated by alcohol dehydrogenase, we hypothesized that there may also be a metabolic interaction between ethanol (ETOH) and BD. We therefore studied, in rats, the plasma PK of GHB, BD and ETOH each at two intravenous (IV) doses, when each substance was given alone, and when GHB or BD was co-administered with ETOH. Results showed that bioconversion of intravenously administered BD to GHB was complete, and that both GHB and BD exhibited nonlinear PK. Various population PK models were analyzed using NONMEM VI, and the best disposition model was found to include two PK compartments each for BD, an (unmeasured) putative semialdehyde intermediate (ALD), GHB and ETOH, the presence of nonlinear (Michaelis-Menten) elimination for each compound, and several mutual inhibition processes. The most prominent mutual metabolic inhibition was found between ETOH and BD, while that between GHB and ETOH was not significant. In vitro studies using liver homogenates confirmed mutual metabolic inhibitions between GHB and BD. Oral absorption of BD was best described by a first-order process with lag-time and pre-systemic metabolism from BD to ALD. Oral absorption of BD (as BD plus ALD) was rapid and complete. The fraction of the absorbed dose entering the central compartment as BD was 30% for the 1.58 mmol/kg dose and 55% for the 6.34 mmol/kg dose. At 6.34 mmol/kg IV, the onset of loss of righting reflex (LRR) for BD was significantly delayed vs. that produced by GHB (72.0 +/- 9.1 min vs. 6.7 +/- 0.6 min, respectively, p < 0.001), and the total duration of LRR was prolonged for BD vs. GHB (192 +/- 28 min vs. 117 +/- 2 min, respectively, p < 0.05). Relative to IV dosing, oral BD produced similar but more variable LRR effects. These results may provide a quantitative PK framework for the understanding of the toxicokinetics and toxicodynamics of both BD and GHB.
- Published
- 2008
- Full Text
- View/download PDF
45. Effects of inhalant nitrites on VEGF expression: a feasible link to Kaposi's sarcoma?
- Author
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Fung HL and Tran DC
- Subjects
- Animals, Humans, Inhalation Exposure, Mice, Nitrites pharmacokinetics, Sarcoma, Kaposi metabolism, Vascular Endothelial Growth Factor A biosynthesis, Gene Expression drug effects, Nitrites administration & dosage, Nitrites toxicity, Sarcoma, Kaposi chemically induced, Vascular Endothelial Growth Factor A drug effects
- Abstract
Because inhalant nitrites (commonly known as "poppers") were thought to be rapidly cleared from the body, the lay literature has somewhat downplayed their toxicity. However, scientific reports have documented their immunosuppressive effects in animals, and epidemiological studies have implicated their use with the development of Kaposi's sarcoma (KS) in humans. Because inhalant nitrites are exogenous nitric oxide donors, we hypothesized that these substances of abuse might exert part of their toxicological effects through this biochemical product, which has been shown to alter gene regulation and angiogenesis. In a series of studies, we showed that acute and chronic in vivo exposure to isobutyl nitrite (a representative inhalant nitrite) produced significant tissue-dependent alterations in the expression of a number of cancer- and angiogenesis-related genes in mice. In particular, hepatic mRNA and protein expression of vascular endothelial growth factor (VEGF) was significantly stimulated. The in vivo growth rate of a subcutaneous VEGF-responsive tumor was also shown to be accelerated by inhalant nitrite exposure. Because the development of KS is extensively linked to VEGF and its receptors, the purported link between inhalant nitrites and KS may be explained mechanistically, at least in part, through the stimulation of VEGF expression by these inhalants.
- Published
- 2006
- Full Text
- View/download PDF
46. Effects of repeated in vivo inhalant nitrite exposure on gene expression in mouse liver and lungs.
- Author
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Tran DC, Brazeau DA, Nickerson PA, and Fung HL
- Subjects
- Administration, Inhalation, Animals, Liver metabolism, Lung metabolism, Mice, Mice, Inbred C57BL, Nitric Oxide Donors pharmacology, Nitric Oxide Synthase genetics, Nitric Oxide Synthase metabolism, Nitrites administration & dosage, Oligonucleotide Array Sequence Analysis, Up-Regulation, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor A metabolism, Gene Expression drug effects, Liver drug effects, Lung drug effects, Nitrites pharmacology
- Abstract
Exposure to inhalant organic nitrites (drugs of abuse commonly known as "poppers") has been reported to enhance tumor growth in mice, but the mechanism is not fully defined. This study examined the effect of repeated in vivo nitrite exposures on gene expression in the mouse liver and lungs using a gene array panel of 94 cancer- and angiogenesis-related genes. Using 2-fold change as a threshold criterion, repeated nitrite exposure was found to alter the expression of 65 and 23 genes in the liver and lungs, respectively. Six genes were significantly upregulated (p
- Published
- 2006
- Full Text
- View/download PDF
47. Visual compatibility of furosemide with phenylephrine and vasopressin.
- Author
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Faria CE, Fiumara K, Patel N, and Tran DC
- Subjects
- Chemistry, Pharmaceutical, Drug Incompatibility, Pharmaceutical Solutions, Adrenergic alpha-Agonists chemistry, Diuretics chemistry, Furosemide chemistry, Hemostatics chemistry, Phenylephrine chemistry, Vasopressins chemistry
- Published
- 2006
- Full Text
- View/download PDF
48. Determination of nitric oxide-donor effects on tissue gene expression in vivo using low-density gene arrays.
- Author
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Tran DC, Brazeau DA, and Fung HL
- Subjects
- Animals, Mice, Mice, Inbred BALB C, Gene Expression drug effects, Nitric Oxide Donors pharmacology, Oligonucleotide Array Sequence Analysis, Tissue Array Analysis
- Abstract
Gene array technology has been used to examine gene expression changes following drug treatments, including administration of nitric oxide (NO) donors. High-density arrays represent a powerful and popular method to analyze a large number of genes simultaneously. On the other hand, low-density arrays, available commercially at a lower cost, allow for the use of gene-specific primers, which reduces the risk of cross-hybridization among genes with similar sequence. For certain experiments in which the hypothesis is focused on a selected set of genes, use of low-density arrays might be more productive and cost-effective. Here, we describe our experience using low-density arrays to examine the effect of exposure to the NO-donor isobutyl nitrite on the expression of 23 cancer- and angiogenesis-related genes in mouse tissues. Detailed descriptions of data capture procedures, statistical tests, and confirmation studies using real-time quantitative (RTQ) reverse transcription polymerase chain reaction (RT-PCR) are presented. Three simple statistical methods, namely Student's t test, significant analysis of microarrays (SAM), and permutation adjusted t statistics (PATS), were applied on our gene array data, and their utilities were compared. All three methods yielded concordant results for the most significant genes, namely vascular endothelial growth factor (VEGF), VEGF receptor 3, Smad5, and Smad7. RT-PCR confirmed VEGF upregulation as observed via gene arrays. PATS appeared to be more robust than SAM in handling our small gene array data set. This statistical method, therefore, appears more suited for analyzing low-density gene array data. We conclude that low-density gene array is a useful screening method that can be performed with lower cost and less cumbersome data treatment.
- Published
- 2005
- Full Text
- View/download PDF
49. Inhalant nitrite exposure alters mouse hepatic angiogenic gene expression.
- Author
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Tran DC, Yeh KC, Brazeau DA, and Fung HL
- Subjects
- Administration, Inhalation, Animals, Cell Line, Gene Expression Regulation, Liver blood supply, Liver drug effects, Male, Mice, Mice, Inbred C57BL, Neoplasms genetics, Neoplasms metabolism, Neovascularization, Physiologic, Nitrites administration & dosage, RNA, Messenger biosynthesis, Reverse Transcriptase Polymerase Chain Reaction, Up-Regulation, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor A metabolism, Vascular Endothelial Growth Factor Receptor-2 biosynthesis, Vascular Endothelial Growth Factor Receptor-2 genetics, Liver metabolism, Nitrites pharmacology, Vascular Endothelial Growth Factor A biosynthesis
- Abstract
Inhalant nitrites are drugs of abuse that have been shown to enhance tumor growth rate in mice and are epidemiologically linked to an increased risk of Kaposi's sarcoma. Because nitrites produce nitric oxide, we hypothesized that their toxicological effects might be partly mediated via regulation of angiogenic factors such as vascular endothelial growth factor (VEGF). Preliminary studies showed that isobutyl nitrite (ISBN) incubation stimulated VEGF protein expression in J774 macrophage cells. C57BL/6 mice exposed to ISBN in air exhibited significant up-regulation of VEGF protein and mRNA in the liver, but not in the lung. Liver mRNA expression of VEGF receptor 2 (VEGFR-2), VEGFR-3, Smad5, and Smad7 was also significantly altered. These results demonstrate that in vivo exposure to an inhalant nitrite results in altered tissue expression of VEGF and its receptors, suggesting that some of its toxicological effects may be mediated partly through a mechanism involving angiogenesis.
- Published
- 2003
- Full Text
- View/download PDF
50. The role of the mouthguard in the prevention of sports-related dental injuries: a review.
- Author
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Newsome PR, Tran DC, and Cooke MS
- Subjects
- Adolescent, Age Factors, Attitude to Health, Basketball injuries, Child, Equipment Design, Female, Football injuries, Health Behavior, Hockey injuries, Humans, Male, Mouth injuries, Orthodontic Appliances, Orthodontics, Corrective instrumentation, Risk Factors, Sex Factors, Surface Properties, Athletic Injuries prevention & control, Mouth Protectors classification, Tooth Injuries prevention & control
- Abstract
Objectives: This paper examines the literature dealing with oral-facial injuries received during participation in sport and the possibilities open to athletes for their prevention. In particular, the paper examines five different aspects of this topic: the risk of dental injury while playing sports, the role of the mouthguard in preventing injury, types of athletic mouthguard, implications for patients undergoing orthodontic treatment and behavioural aspects of mouthguard wear., Results: It is clear from this review that participation in a number of sports does carry a considerable risk of sustaining dental injury, not only in the so-called contact sports such as rugby and hockey, but also in less obviously dangerous sports such as basketball. Although some evidence exists to the contrary, the majority of studies have found the mouthguard to be the most effective way of preventing such injuries. It is also clear that the custom-fabricated mouthguard, in particular the pressure-laminated variety, is seen to afford most protection. Athletes undergoing orthodontic treatment present a particular problem as they are potentially at greater risk of injury because of increased tooth mobility and the presence of orthodontic appliances. The fabrication of mouthguards for these patients is also problematic and the literature covering this is reviewed. As with other preventive measures, mouthguard usage is often less than the dental profession would like; the reasons for this are explored in a small number of studies., Conclusion: While much progress has been made in this area, the profession could do much more to promote the greater use of mouthguards.
- Published
- 2001
- Full Text
- View/download PDF
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