Telomeres protect against chromosomal end damage and shorten with each cell division; their lengt... more Telomeres protect against chromosomal end damage and shorten with each cell division; their length may be a marker of cardiovascular and overall biological aging. We examined the hypothesis that reduced telomere length is associated with increased coronary atherosclerosis in rheumatoid arthritis (RA). We performed a cross-sectional study in 145 patients with RA and 87 control subjects frequency-matched for age, race, and sex. Coronary artery calcium score was determined by noncontrast cardiac computed tomography. Telomere length was measured from whole blood DNA, using real-time quantitative polymerase chain reaction and expressed as telomeric product to a single-copy gene product ratio (T/S ratio). Associations between telomere length, coronary artery calcium score, and 28-joint Disease Activity Score (DAS28) were assessed with Spearman correlation, proportional odds logistic regression, and linear regression, adjusting for age, race, and sex. Telomere length was significantly inve...
Clinical Journal of the American Society of Nephrology, 2015
Electronic health record (EHR) patient portals allow individuals to access their medical informat... more Electronic health record (EHR) patient portals allow individuals to access their medical information with the intent of patient empowerment. However, little is known about portal use in nephrology patients. We addressed this gap by characterizing adoption of an EHR portal, assessing secular trends, and examining the association of portal adoption and BP control (<140/90 mmHg). Patients seen between January 1, 2010, and December 31, 2012, at any of four university-affiliated nephrology offices who had at least one additional nephrology follow-up visit before June 30, 2013, were included. Sociodemographic characteristics, comorbidities, clinical measurements, and office visits were abstracted from the EHR. Neighborhood median household income was obtained from the American Community Survey 2012. Of 2803 patients, 1098 (39%) accessed the portal. Over 87% of users reviewed laboratory results, 85% reviewed their medical information (e.g., medical history), 85% reviewed or altered appointments, 77% reviewed medications, 65% requested medication refills, and 31% requested medical advice from their renal provider. In adjusted models, older age, African-American race (odds ratio [OR], 0.50; 95% confidence interval [95% CI], 0.39 to 0.64), Medicaid status (OR, 0.53; 95% CI, 0.36 to 0.77), and lower neighborhood median household income were associated with not accessing the portal. Portal adoption increased over time (2011 versus 2010: OR, 1.38 [95% CI, 1.09 to 1.75]; 2012 versus 2010: OR, 1.95 [95% CI, 1.44 to 2.64]). Portal adoption was correlated with BP control in patients with a diagnosis of hypertension; however, in the fully adjusted model this was somewhat attenuated and no longer statistically significant (OR, 1.11; 95% CI, 0.99 to 1.24). While portal adoption appears to be increasing, greater attention is needed to understand why vulnerable populations do not access it. Future research should examine barriers to the use of e-health technologies in underserved patients with CKD, interventions to address them, and their potential to improve outcomes.
It has been shown that arbaclofen placarbil (AP) inhibits reflux in gastroesophageal reflux disea... more It has been shown that arbaclofen placarbil (AP) inhibits reflux in gastroesophageal reflux disease (GERD) following single oral dosing. This study evaluated the efficacy and safety of AP over 4 weeks in subjects with symptomatic GERD. One hundred fifty-six subjects with heartburn and/or regurgitation ≥3 days/week and either no history of taking proton pump inhibitors (PPIs naive, n=58) or at least partial symptom response to PPI therapy (PPI responsive, n=98) were enrolled in this randomized, double-blind, placebo-controlled trial. All GERD therapies including PPIs were discontinued 2 weeks before randomization to AP 20, 40, or 60 mg daily, 30 mg twice daily, or placebo for 4 weeks. Randomization was stratified by prior PPI use. In the primary analysis, change from baseline in weekly heartburn events between AP and placebo for the entire study group was not statistically significant. However, a significant interaction was observed between prior PPI use and response to AP treatment. In pre-planned secondary analyses of the PPI-responsive subgroup, percent reductions from baseline in weekly heartburn events were greater for each AP dose vs. placebo (P<0.05) and the percentage of subjects who reported complete resolution of heartburn during week 4 was higher in each AP treatment group (21, 28, 30, and 50% for AP 20, 40, 60 mg daily, and 30 mg twice daily, respectively) compared with placebo (6%) (P<0.05 for 30 mg twice daily). Corresponding analyses of the PPI-naive subgroup showed no significant differences. AP was well tolerated; withdrawals due to adverse events were infrequent. AP was not superior to placebo in reducing the number of weekly heartburn events over 4 weeks in the primary analysis of the entire study population. Exploratory subgroup analyses suggest that response to PPI treatment before the study was associated with a response to AP treatment.
The efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in preventing recurrence of atria... more The efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in preventing recurrence of atrial fibrillation (AF) is controversial and their effects on inflammation and oxidative stress in this population are not known. This study examined the effects of high-dose marine n-3 PUFAs added to conventional therapy on the recurrence of AF and on markers of inflammation and oxidative stress. Patients with paroxysmal or persistent AF were randomized to n-3 PUFAs (4 g/day; n = 126) or placebo (n = 64) in a 2:1 ratio in a prospective, double-blind, placebo-controlled, parallel group study. The primary outcome was time to recurrence of AF. Secondary outcomes were changes in biomarkers of inflammation (serum interleukin [IL]-6, IL-8, IL-10, tissue necrosis factor alpha, monocyte chemoattractant protein-1, and vascular endothelial growth factor), N-terminal-pro-brain-type natriuretic peptide, and oxidative stress (urinary F2-isoprostanes). AF recurred in 74 patients (58.7%) randomized to n-3...
Hypertension (HTN), a common modifiable cardiovascular risk factor, is more common in patients wi... more Hypertension (HTN), a common modifiable cardiovascular risk factor, is more common in patients with rheumatoid arthritis (RA), but the underlying mechanisms are unclear. We examined the hypothesis that mediators of inflammation and markers of cardiovascular risk are associated with HTN in RA. We compared measures of inflammation [serum C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), homocysteine, and leptin concentrations] and insulin resistance [homeostasis model assessment index (HOMA)] in RA patients with (n = 90) and without HTN (n = 79). HTN was defined as blood pressure ≥ 140/90 mm Hg or treatment with antihypertensive therapy. The independent association of markers of interest with HTN was examined using multivariable logistic regression. Patients with HTN were significantly older and had longer disease duration than those without HTN (both p < 0.001). Concentrations of homocysteine [11.1 (8.5-13.5) μmol/l vs 9.3 (7.8-11.0) μmol/l] were significantly higher in patients with HTN (p < 0.001). After adjustment for age, sex, race, smoking, body mass index, and corticosteroid and nonsteroidal antiinflammatory drugs (NSAID) use, increased concentrations of homocysteine (OR 2.9, 95% CI: 1.5-5.5, p = 0.001), and leptin (OR 2.0, 95% CI: 1.0-3.8, p = 0.046) were significantly associated with HTN, but the 28-joint Disease Activity Score, IL-6, CRP, TNF-α, and HOMA index were not (all p > 0.05). HTN in patients with RA is not associated with generalized systemic inflammation or insulin resistance, but is associated with increasing concentrations of homocysteine and leptin. The pathogenesis of HTN in RA may involve pathways more regularly associated with fat and vascular homeostasis.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2013
F₂-isoprostanes (F₂-IsoP) are oxidant stress biomarkers that are higher in HIV-infected women tha... more F₂-isoprostanes (F₂-IsoP) are oxidant stress biomarkers that are higher in HIV-infected women than men. We explored whether the effect of hemoglobin (Hgb), serum iron, or anemia on F₂-IsoP is different between HIV-infected women and men. Plasma F₂-IsoP were quantified by gas chromatography/mass spectrometry; clinical and laboratory data were collected at enrollment or from the medical record. Multivariable linear regression was used to assess associations between F₂-IsoP and Hgb, anemia as a dichotomous variable, and serum iron with adjustment for age, sex, race, body mass index, CD4 lymphocyte count, self-reported current smoking status, and antiretroviral therapy. Compared with men, women had lower Hgb [median: 12.7 (interquartile range: 11.8-13.9) vs. 14.9 (13.7-15.8) g/dL, P < 0.001], lower iron levels [75 (47-97) vs. 90 (69-121) µg/dL, P = 0.004], more anemia (29% vs. 10%, P < 0.001), and higher levels of F₂-IsoP [42 (32-62) vs. 36 (25-46) pg/mL, P < 0.001]. The relationship between iron and F₂-IsoP differed significantly between men and women (interaction P = 0.02). Men had a 21% (95% confidence interval: 8 to 36) increase in F₂-IsoP per interquartile increase in iron (P = 0.001), whereas no relationship was seen among women [-4% (-17 to 13, P = 0.65]. Although women have overall higher F₂-IsoP than men, a relationship between circulating F₂-IsoP and iron levels was observed in men but not in women with HIV infection. The association between female sex and higher F₂-IsoP is not explained by iron or Hgb levels because the association persists when controlling for these factors. The role of iron in oxidant stress and sex-specific differences among HIV-infected individuals require further study.
BACKROUND: Epithelial-mesenchymal transition (EMT) changes polarized epithelial cells into migrat... more BACKROUND: Epithelial-mesenchymal transition (EMT) changes polarized epithelial cells into migratory phenotypes associated with loss of cell-cell adhesion molecules and cytoskeletal rearrangements. This form of plasticity is seen in mesodermal development, fibroblast formation, and cancer metastasis. METHODS AND FINDINGS: Here we identify prominent transcriptional networks active during three time points of this transitional process, as epithelial cells become fibroblasts. DNA microarray in cultured epithelia undergoing EMT, validated in vivo, were used to detect various patterns of gene expression. In particular, the promoter sequences of differentially expressed genes and their transcription factors were analyzed to identify potential binding sites and partners. The four most frequent cis-regulatory elements (CREs) in up-regulated genes were SRY, FTS-1, Evi-1, and GC-Box, and RNA inhibition of the four transcription factors, Atf2, Klf10, Sox11, and SP1, most frequently binding the...
Telomeres protect against chromosomal end damage and shorten with each cell division; their lengt... more Telomeres protect against chromosomal end damage and shorten with each cell division; their length may be a marker of cardiovascular and overall biological aging. We examined the hypothesis that reduced telomere length is associated with increased coronary atherosclerosis in rheumatoid arthritis (RA). We performed a cross-sectional study in 145 patients with RA and 87 control subjects frequency-matched for age, race, and sex. Coronary artery calcium score was determined by noncontrast cardiac computed tomography. Telomere length was measured from whole blood DNA, using real-time quantitative polymerase chain reaction and expressed as telomeric product to a single-copy gene product ratio (T/S ratio). Associations between telomere length, coronary artery calcium score, and 28-joint Disease Activity Score (DAS28) were assessed with Spearman correlation, proportional odds logistic regression, and linear regression, adjusting for age, race, and sex. Telomere length was significantly inve...
Clinical Journal of the American Society of Nephrology, 2015
Electronic health record (EHR) patient portals allow individuals to access their medical informat... more Electronic health record (EHR) patient portals allow individuals to access their medical information with the intent of patient empowerment. However, little is known about portal use in nephrology patients. We addressed this gap by characterizing adoption of an EHR portal, assessing secular trends, and examining the association of portal adoption and BP control (<140/90 mmHg). Patients seen between January 1, 2010, and December 31, 2012, at any of four university-affiliated nephrology offices who had at least one additional nephrology follow-up visit before June 30, 2013, were included. Sociodemographic characteristics, comorbidities, clinical measurements, and office visits were abstracted from the EHR. Neighborhood median household income was obtained from the American Community Survey 2012. Of 2803 patients, 1098 (39%) accessed the portal. Over 87% of users reviewed laboratory results, 85% reviewed their medical information (e.g., medical history), 85% reviewed or altered appointments, 77% reviewed medications, 65% requested medication refills, and 31% requested medical advice from their renal provider. In adjusted models, older age, African-American race (odds ratio [OR], 0.50; 95% confidence interval [95% CI], 0.39 to 0.64), Medicaid status (OR, 0.53; 95% CI, 0.36 to 0.77), and lower neighborhood median household income were associated with not accessing the portal. Portal adoption increased over time (2011 versus 2010: OR, 1.38 [95% CI, 1.09 to 1.75]; 2012 versus 2010: OR, 1.95 [95% CI, 1.44 to 2.64]). Portal adoption was correlated with BP control in patients with a diagnosis of hypertension; however, in the fully adjusted model this was somewhat attenuated and no longer statistically significant (OR, 1.11; 95% CI, 0.99 to 1.24). While portal adoption appears to be increasing, greater attention is needed to understand why vulnerable populations do not access it. Future research should examine barriers to the use of e-health technologies in underserved patients with CKD, interventions to address them, and their potential to improve outcomes.
It has been shown that arbaclofen placarbil (AP) inhibits reflux in gastroesophageal reflux disea... more It has been shown that arbaclofen placarbil (AP) inhibits reflux in gastroesophageal reflux disease (GERD) following single oral dosing. This study evaluated the efficacy and safety of AP over 4 weeks in subjects with symptomatic GERD. One hundred fifty-six subjects with heartburn and/or regurgitation ≥3 days/week and either no history of taking proton pump inhibitors (PPIs naive, n=58) or at least partial symptom response to PPI therapy (PPI responsive, n=98) were enrolled in this randomized, double-blind, placebo-controlled trial. All GERD therapies including PPIs were discontinued 2 weeks before randomization to AP 20, 40, or 60 mg daily, 30 mg twice daily, or placebo for 4 weeks. Randomization was stratified by prior PPI use. In the primary analysis, change from baseline in weekly heartburn events between AP and placebo for the entire study group was not statistically significant. However, a significant interaction was observed between prior PPI use and response to AP treatment. In pre-planned secondary analyses of the PPI-responsive subgroup, percent reductions from baseline in weekly heartburn events were greater for each AP dose vs. placebo (P<0.05) and the percentage of subjects who reported complete resolution of heartburn during week 4 was higher in each AP treatment group (21, 28, 30, and 50% for AP 20, 40, 60 mg daily, and 30 mg twice daily, respectively) compared with placebo (6%) (P<0.05 for 30 mg twice daily). Corresponding analyses of the PPI-naive subgroup showed no significant differences. AP was well tolerated; withdrawals due to adverse events were infrequent. AP was not superior to placebo in reducing the number of weekly heartburn events over 4 weeks in the primary analysis of the entire study population. Exploratory subgroup analyses suggest that response to PPI treatment before the study was associated with a response to AP treatment.
The efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in preventing recurrence of atria... more The efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in preventing recurrence of atrial fibrillation (AF) is controversial and their effects on inflammation and oxidative stress in this population are not known. This study examined the effects of high-dose marine n-3 PUFAs added to conventional therapy on the recurrence of AF and on markers of inflammation and oxidative stress. Patients with paroxysmal or persistent AF were randomized to n-3 PUFAs (4 g/day; n = 126) or placebo (n = 64) in a 2:1 ratio in a prospective, double-blind, placebo-controlled, parallel group study. The primary outcome was time to recurrence of AF. Secondary outcomes were changes in biomarkers of inflammation (serum interleukin [IL]-6, IL-8, IL-10, tissue necrosis factor alpha, monocyte chemoattractant protein-1, and vascular endothelial growth factor), N-terminal-pro-brain-type natriuretic peptide, and oxidative stress (urinary F2-isoprostanes). AF recurred in 74 patients (58.7%) randomized to n-3...
Hypertension (HTN), a common modifiable cardiovascular risk factor, is more common in patients wi... more Hypertension (HTN), a common modifiable cardiovascular risk factor, is more common in patients with rheumatoid arthritis (RA), but the underlying mechanisms are unclear. We examined the hypothesis that mediators of inflammation and markers of cardiovascular risk are associated with HTN in RA. We compared measures of inflammation [serum C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), homocysteine, and leptin concentrations] and insulin resistance [homeostasis model assessment index (HOMA)] in RA patients with (n = 90) and without HTN (n = 79). HTN was defined as blood pressure ≥ 140/90 mm Hg or treatment with antihypertensive therapy. The independent association of markers of interest with HTN was examined using multivariable logistic regression. Patients with HTN were significantly older and had longer disease duration than those without HTN (both p < 0.001). Concentrations of homocysteine [11.1 (8.5-13.5) μmol/l vs 9.3 (7.8-11.0) μmol/l] were significantly higher in patients with HTN (p < 0.001). After adjustment for age, sex, race, smoking, body mass index, and corticosteroid and nonsteroidal antiinflammatory drugs (NSAID) use, increased concentrations of homocysteine (OR 2.9, 95% CI: 1.5-5.5, p = 0.001), and leptin (OR 2.0, 95% CI: 1.0-3.8, p = 0.046) were significantly associated with HTN, but the 28-joint Disease Activity Score, IL-6, CRP, TNF-α, and HOMA index were not (all p > 0.05). HTN in patients with RA is not associated with generalized systemic inflammation or insulin resistance, but is associated with increasing concentrations of homocysteine and leptin. The pathogenesis of HTN in RA may involve pathways more regularly associated with fat and vascular homeostasis.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2013
F₂-isoprostanes (F₂-IsoP) are oxidant stress biomarkers that are higher in HIV-infected women tha... more F₂-isoprostanes (F₂-IsoP) are oxidant stress biomarkers that are higher in HIV-infected women than men. We explored whether the effect of hemoglobin (Hgb), serum iron, or anemia on F₂-IsoP is different between HIV-infected women and men. Plasma F₂-IsoP were quantified by gas chromatography/mass spectrometry; clinical and laboratory data were collected at enrollment or from the medical record. Multivariable linear regression was used to assess associations between F₂-IsoP and Hgb, anemia as a dichotomous variable, and serum iron with adjustment for age, sex, race, body mass index, CD4 lymphocyte count, self-reported current smoking status, and antiretroviral therapy. Compared with men, women had lower Hgb [median: 12.7 (interquartile range: 11.8-13.9) vs. 14.9 (13.7-15.8) g/dL, P < 0.001], lower iron levels [75 (47-97) vs. 90 (69-121) µg/dL, P = 0.004], more anemia (29% vs. 10%, P < 0.001), and higher levels of F₂-IsoP [42 (32-62) vs. 36 (25-46) pg/mL, P < 0.001]. The relationship between iron and F₂-IsoP differed significantly between men and women (interaction P = 0.02). Men had a 21% (95% confidence interval: 8 to 36) increase in F₂-IsoP per interquartile increase in iron (P = 0.001), whereas no relationship was seen among women [-4% (-17 to 13, P = 0.65]. Although women have overall higher F₂-IsoP than men, a relationship between circulating F₂-IsoP and iron levels was observed in men but not in women with HIV infection. The association between female sex and higher F₂-IsoP is not explained by iron or Hgb levels because the association persists when controlling for these factors. The role of iron in oxidant stress and sex-specific differences among HIV-infected individuals require further study.
BACKROUND: Epithelial-mesenchymal transition (EMT) changes polarized epithelial cells into migrat... more BACKROUND: Epithelial-mesenchymal transition (EMT) changes polarized epithelial cells into migratory phenotypes associated with loss of cell-cell adhesion molecules and cytoskeletal rearrangements. This form of plasticity is seen in mesodermal development, fibroblast formation, and cancer metastasis. METHODS AND FINDINGS: Here we identify prominent transcriptional networks active during three time points of this transitional process, as epithelial cells become fibroblasts. DNA microarray in cultured epithelia undergoing EMT, validated in vivo, were used to detect various patterns of gene expression. In particular, the promoter sequences of differentially expressed genes and their transcription factors were analyzed to identify potential binding sites and partners. The four most frequent cis-regulatory elements (CREs) in up-regulated genes were SRY, FTS-1, Evi-1, and GC-Box, and RNA inhibition of the four transcription factors, Atf2, Klf10, Sox11, and SP1, most frequently binding the...
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Papers by A. Bian