Browsing by Author "Yu, Zhangsheng"
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Item Adiposity has unique influence on the renin-aldosterone axis and blood pressure in black children(Elsevier, 2013-11) Yu, Zhangsheng; Eckert, George; Liu, Hai; Pratt, J. Howard; Tu, Wanzhu; Medicine, School of MedicineOBJECTIVE: To comparatively examine the effects of adiposity on the levels of plasma renin activity (PRA), plasma aldosterone concentration (PAC), and aldosterone-renin ratio (ARR) in young black and white children. STUDY DESIGN: We prospectively assessed 248 black and 345 white children and adolescents. A novel analytical technique was used to assess the concurrent influences of age and body mass index (BMI) on PRA, PAC, and ARR. The estimated effects were depicted by colored contour plots. RESULTS: In contrast to whites, blacks had lower PRA (2.76 vs 3.36 ng/mL/h; P < .001) and lower PAC (9.01 vs 14.59 ng/dL; P < .001). In blacks, BMI was negatively associated with PRA (P = .001), consistent with an association with a more expanded plasma volume; there was no association with PAC. In whites, BMI was positively associated with PAC (P = .005); we did not detect a BMI-PRA association. The effects of BMI on ARR were directionally similar in the two race groups but more pronounced in blacks. Mean systolic blood pressure was greater in blacks with lower PRA (P < .01), higher PAC (P = .015), and higher ARR (P = .49). CONCLUSIONS: An increase in adiposity was associated with a suppressed PRA in blacks and an increase in PAC in whites. The unique relationship between adiposity and renin-aldosterone axis in blacks suggests the possible existence of a population-specific mechanism characterized by volume expansion, which could in turn enhance the influences of adiposity on blood pressure in black children and adolescents.Item Apurinic/Apyrimidinic Endonuclease/Redox Factor-1 (APE1/Ref-1) redox function negatively regulates NRF2(2015-01) Fishel, Melissa L.; Wu, Xue; Devlin, Cecilia M.; Logsdon, Derek P.; Jiang, Yanlin; Luo, Meihua; He, Ying; Yu, Zhangsheng; Tong, Yan; Lipking, Kelsey P.; Maitra, Anirban; Rajeshkumar, N. V.; Scandura, Glenda; Kelley, Mark R.; Ivan, Mircea; Department of Pediatrics, Indiana University School of MedicineApurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) (henceforth referred to as Ref-1) is a multifunctional protein that in addition to its base excision DNA repair activity exerts redox control of multiple transcription factors, including nuclear factor κ-light chain enhancer of activated B cells (NF-κB), STAT3, activator protein-1 (AP-1), hypoxia-inducible factor-1 (HIF-1), and tumor protein 53 (p53). In recent years, Ref-1 has emerged as a promising therapeutic target in cancer, particularly in pancreatic ductal carcinoma. Although a significant amount of research has centered on Ref-1, no wide-ranging approach had been performed on the effects of Ref-1 inhibition and transcription factor activity perturbation. Starting with a broader approach, we identified a previously unsuspected effect on the nuclear factor erythroid-related factor 2 (NRF2), a critical regulator of cellular defenses against oxidative stress. Based on genetic and small molecule inhibitor-based methodologies, we demonstrated that repression of Ref-1 potently activates NRF2 and its downstream targets in a dose-dependent fashion, and that the redox, rather than the DNA repair function of Ref-1 is critical for this effect. Intriguingly, our results also indicate that this pathway does not involve reactive oxygen species. The link between Ref-1 and NRF2 appears to be present in all cells tested in vitro, noncancerous and cancerous, including patient-derived tumor samples. In particular, we focused on understanding the implications of the novel interaction between these two pathways in primary pancreatic ductal adenocarcinoma tumor cells and provide the first evidence that this mechanism has implications for overcoming the resistance against experimental drugs targeting Ref-1 activity, with clear translational implications.Item Associations between menarche-related genetic variants and pubertal growth in male and female adolescents(Elsevier, 2015-01) Tu, Wanzhu; Wagner, Erin K.; Eckert, George J.; Yu, Zhangsheng; Hannon, Tamara; Pratt, J. Howard; He, Chunyan; Department of Epidemiology, School of Public HealthPURPOSE: Previous studies have identified novel genetic variants associated with age at menarche in females of European descent. The pubertal growth effects of these variants have not been carefully evaluated in non-European descent groups. We aimed to examine the effects of 31 newly identified menarche-related single-nucleotide polymorphisms (SNPs) on growth outcomes in African-American (AA) and European-American (EA) children in a prospective cohort. METHODS: We analyzed longitudinal data collected from 263 AAs and 338 EAs enrolled between ages 5 and 17 years; the subjects were followed semiannually for an average of 6 years. The associations between the SNPs and growth-related outcomes, including weight, height, and body mass index (BMI), were examined using mixed-effect models. RESULTS: Longitudinal analyses revealed that 4 (near or in genes VGLL3, PEX2, CA10, and SKOR2) of the 14 menarche-only-related SNPs were associated with changes in weight and BMI in EA and AA (p ≤ .0032), but none of them was associated with changes in height. Of the eight menarche-timing and BMI-related SNPs, none was associated with changes in height, but three (in or near genes NEGR1, ETV5, and FTO) were associated with more rapid increases in weight and/or BMI in EA (p ≤ .0059). Among the nine menarche-timing and height-related SNPs, four (in or near genes ZBTB38, LOC728666, TBX2, and CABLES) were associated with changes in weight or height in EA and AA (p ≤ .0042). CONCLUSIONS: Genetic variants related to age at menarche were found to be associated with various growth parameters in healthy adolescents. The identified associations were often race and sex specific.Item Comparative Responsiveness of the PROMIS Pain Interference Short Forms, Brief Pain Inventory, PEG, and SF-36 Bodily Pain Subscale(Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2016-04) Kean, Jacob; Monahan, Patrick O.; Kroenke, Kurt; Wu, Jingwei; Yu, Zhangsheng; Stump, Tim E.; Krebs, Erin E.; Biostatistics, School of Public HealthPURPOSE: To compare the sensitivity to change and the responsiveness to intervention of the PROMIS Pain Interference short forms, Brief Pain Inventory (BPI), 3-item PEG scale, and SF-36 Bodily Pain subscale in a sample of patients with persistent musculoskeletal pain of moderate severity. METHODS: Standardized response means, standardized effect sizes, and receiver operating curve analyses were used to assess change between baseline and 3-month assessments in 250 participants who participated in a randomized clinical effectiveness trial of collaborative telecare management for moderate to severe and persistent musculoskeletal pain. RESULTS: The BPI, PEG, and SF-36 Bodily Pain measures were more sensitive to patient-reported global change than the PROMIS Pain Interference short forms, especially for the clinically improved group, for which the change detected by the PROMIS short forms was not statistically significant. The BPI was more responsive to the clinical intervention than the SF-36 Bodily Pain and PROMIS Pain Interference measures. Post hoc analyses exploring these findings did not suggest that differences in content or rating scale structure (number of response options or anchoring language) adequately explained the observed differences in the detection of change. CONCLUSIONS: In this clinical trial, the BPI and PEG measures were better able to detect change than the SF-36 Bodily Pain and PROMIS Pain Interference measures.Item Determination of the composition of failure time models with long-term survivors(2016-12-08) Masud, Abdullah Al; Tu, Wanzhu; Yu, ZhangshengFailure-time data with long-term survivors are frequently encountered in clinical in vestigations. A standard approach for analyzing such data is to add a logistic regres sion component to the traditional proportional hazard models for accommodation of the individuals that are not at risk of the event. One such formulation is the cure rate model; other formulations with similar structures are also used in prac tice. Increased complexity presents a great challenge for determination of the model composition. Importantly, no existing model selection tools are directly applicable for determination of the composition of such models. This dissertation focuses on two key questions concerning the construction of complex survival models with long term survivors: (1) what independent variables should be included in which modeling components? (2) what functional form should each variable assume? I address these questions by proposing a set of regularized estimation procedures using the Least Absolute Shrinkage and Selection Operators (LASSO). Specifically, I present vari able selection and structural discovery procedures for a broad class of survival models with long-term survivors. Selection performance of the proposed methods is evaluated through carefully designed simulation studies.Item Does comorbid chronic pain affect posttraumatic stress disorder diagnosis and treatment? Outcomes of posttraumatic stress disorder screening in Department of Veterans Affairs primary care(2016) Outcalt, Samantha D.; Hoen, Helena Maria; Yu, Zhangsheng; Franks, Tenesha Marie; Krebs, Erin E.; Department of Psychiatry, IU School of MedicineBecause posttraumatic stress disorder (PTSD) is both prevalent and underrecognized, routine primary care-based screening for PTSD has been implemented across the Veterans Health Administration. PTSD is frequently complicated by the presence of comorbid chronic pain, and patients with both conditions have increased symptom severity and poorer prognosis. Our objective was to determine whether the presence of pain affects diagnosis and treatment of PTSD among Department of Veterans Affairs (VA) patients who have a positive PTSD screening test. This retrospective cohort study used clinical and administrative data from six Midwestern VA medical centers. We identified 4,244 VA primary care patients with a positive PTSD screen and compared outcomes for those with and without a coexisting pain diagnosis. Outcomes were three clinically appropriate responses to positive PTSD screening: (1) mental health visit, (2) PTSD diagnosis, and (3) new selective serotonin reuptake inhibitor (SSRI) prescription. We found that patients with coexisting pain had a lower rate of mental health visits than those without pain (hazard ratio: 0.889, 95% confidence interval: 0.821–0.962). There were no significant differences in the rate of PTSD diagnosis or new SSRI prescription between patients with and without coexisting pain.Item The effect of a locally adapted, secondary stroke risk factor self-management program on medication adherence among veterans with stroke/TIA(Springer, 2016-09) Damush, Teresa M.; Myers, Laura; Anderson, Jane A.; Yu, Zhangsheng; Ofner, Susan; Nicholas, Gloria; Kimmel, Barbara; Schmid, Arlene A.; Kent, Thomas; Williams, Linda S.; Department of Medicine, IU School of MedicineWe targeted stroke/transient ischemic attack (TIA) survivors to engage in self-management practices to manage secondary stroke risk factors. We conducted a randomized, regional pilot trial of a locally adapted, secondary stroke prevention program. We implemented the program at two Veterans Administration Medical Centers. Program sessions targeted stroke risk factor self-management. Specifically, we evaluated the effect of the program on the reach, implementation, and effectiveness on patient self-efficacy; stroke-specific, health-related quality of life; and medication adherence for the prevalent stroke risk factors: (1) diabetes, (2) hypertension, and (3) hyperlipidemia. Medication possession ratios were calculated to evaluate medication adherence using VA pharmacy benefits data pre (6 months prior) and post (6 months after) the stroke/TIA event. Based upon the literature standard of 80 % compliance rate, we dichotomized compliance and modeled the data using logistical regression. Final sample included 174 veterans with an acute stroke or TIA who were randomized to receive either the intervention (n = 87) or attention control program (n = 87). Patient self-efficacy and stroke-specific, health-related quality of life at 6 months did not significantly differ between groups. We found improvements in medication adherence within the intervention group. In the intervention group, the odds of compliance with diabetes medications post-stroke were significantly larger than the odds of compliance prior to the stroke (odds ratio = 3.45 (95 % CI = 1.08–10.96). For compliance to hypertension medications, the intervention group showed significantly greater odds of compliance post intervention than pre intervention (odds ratio = 3. 68 (95 % CI = 1.81–7.48). The control group showed no difference in compliance rates from baseline to follow-up. For adherence to hypercholesterolemia medications, both the intervention (odds ratio = 5.98 (95 % CI = 2.81–12.76) and control groups (odds ratio = 3.83 (95 % CI = 1.83–8.01), had significant increases in the odds of compliance to statin medications; however, the comparison of changes in log odds of compliance between these two groups showed that the increases were not significantly different. We observed within group improvements in medication adherence among those receiving a post-stroke risk factor self-management program suggesting that a self-management format may be feasible to enable adherence to prescribed medications to reduce secondary stroke risk after stroke in concordance with guideline care. Additional research is needed to enhance intervention components to improve effectiveness outcomes.Item Erratum to: The effect of a locally adapted, secondary stroke risk factor self-management program on medication adherence among veterans with stroke(Springer, 2016-09) Damush, Teresa M.; Myers, Laura; Anderson, Jane A.; Yu, Zhangsheng; Ofner, Susan; Nicholas, Gloria; Kimmel, Barbara; Schmid, Arlene A.; Kent, Thomas; Williams, Linda S.; Department of Medicine, IU School of MedicineItem Evaluation of Stepped Care for Chronic Pain (ESCAPE) in Veterans of the Iraq and Afghanistan Conflicts A Randomized Clinical Trial(AMA, 2015-05) Bair, Matthew J.; Ang, Dennis; Wu, Jingwei; Outcalt, Samantha D.; Sargent, Christy; Kempf, Carol; Froman, Amanda; Schmid, Arlena A.; Damush, Teresa M.; Yu, Zhangsheng; Davis, Louanne W.; Kroenke, Kurt; Department of Medicine, IU School of MedicineIMPORTANCE: Despite the prevalence and the functional, psychological, and economic impact of chronic pain, few intervention studies of treatment of chronic pain in veterans have been performed. OBJECTIVE: To determine whether a stepped-care intervention is more effective than usual care, as hypothesized, in reducing pain-related disability, pain interference, and pain severity. DESIGN, SETTING, AND PARTICIPANTS: We performed a randomized clinical trial comparing stepped care with usual care for chronic pain. We enrolled 241 veterans from Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn with chronic (>3 months) and disabling (Roland Morris Disability Scale score, ≥7) musculoskeletal pain of the cervical or lumbar spine or extremities (shoulders, knees, and hips) in the Evaluation of Stepped Care for Chronic Pain (ESCAPE) trial from December 20, 2007, through June 30, 2011. The 9-month follow-up was completed by April 2012. Patients received treatment at a postdeployment clinic and 5 general medicine clinics at a Veterans Affairs medical center. INTERVENTIONS: Step 1 included 12 weeks of analgesic treatment and optimization according to an algorithm coupled with pain self-management strategies; step 2, 12 weeks of cognitive behavioral therapy. All intervention aspects were delivered by nurse care managers. MAIN OUTCOMES AND MEASURES: Pain-related disability (Roland Morris Disability Scale), pain interference (Brief Pain Inventory), and pain severity (Graded Chronic Pain Scale). RESULTS: The primary analysis included 121 patients receiving the stepped-care intervention and 120 patients receiving usual care. At 9 months, the mean decrease from baseline in the Roland Morris Disability Scale score was 1.7 (95% CI, -2.6 to -0.9) points in the usual care group and 3.7 (95% CI, -4.5 to -2.8) points in the intervention group (between-group difference, -1.9 [95% CI, -3.2 to -0.7] points; P=.002). The mean decrease from baseline in the Pain Interference subscale score of the Brief Pain Inventory was 0.9 points in the usual care group and 1.7 points in the intervention group (between-group difference, -0.8 [95% CI, -1.3 to -0.3] points; P=.003). The Graded Chronic Pain Scale severity score was reduced by 4.5 points in the usual care group and 11.1 points in the intervention group (between-group difference, -6.6 [95% CI, -10.5 to -2.7] points; P=.001). CONCLUSIONS AND RELEVANCE: A stepped-care intervention that combined analgesics, self-management strategies, and brief cognitive behavioral therapy resulted in statistically significant reductions in pain-related disability, pain interference, and pain severity in veterans with chronic musculoskeletal pain.Item Exhaled nitric oxide during infancy as a risk factor for asthma and airway hyperreactivity(European Respiratory Society, 2015-01) Chang, Daniel; Yao, Weiguo; Tiller, Christina J.; Kisling, Jeffrey; Slaven, James E.; Yu, Zhangsheng; Kaplan, Mark H.; Tepper, Robert S.; Department of Pediatrics, IU School of MedicineChildhood asthma is often characterised by elevated exhaled nitric oxide (eNO), decreased lung function, increased airway reactivity and atopy; however, our understanding of when these phenotypic airway characteristics develop remains unclear. This study evaluated whether eNO, lung function, airway reactivity and immune characteristics during infancy are risk factors of asthma at age 5 years. Infants with eczema, enrolled prior to wheezy illness (n=116), had eNO, spirometry, airway reactivity and allergen sensitisation assessed at entry to the study and repeated at age 5 years (n=90). Increasing eNO at entry was associated with an increased risk of asthma (p=0.037) and increasing airway reactivity (p=0.015) at age 5 years. Children with asthma at 5 years of age had a greater increase in eNO between infancy and age 5 years compared with those without asthma (p=0.002). Egg sensitisation at entry was also associated with an increased risk of asthma (p=0.020), increasing eNO (p = 0.002) and lower forced expiratory flows (p=0.029) as a 5 year-old. Our findings suggest that, among infants at high risk for developing asthma, eNO early in life may provide important insights into the subsequent risk of asthma and its airway characteristics.