ASU Scholarship Showcase

S-cysteinylated albumin and methionine-oxidized apolipoprotein A-I (apoA-I) have been posed as candidate markers of diseases associated with oxidative stress. Here, a dilute-and-shoot form of LC–electrospray ionization–MS requiring half a microliter of blood plasma was employed to simultaneously quantify the relative abundance of these oxidized proteoforms in samples stored at −80 °C, −20 °C, and room temperature and exposed to multiple freeze-thaw cycles and other adverse conditions in order to assess the possibility that protein oxidation may occur as a result of poor sample storage or handling. Samples from a healthy donor and a participant with poorly controlled type 2 diabetes started at the same low level of protein oxidation and behaved similarly; significant increases in albumin oxidation via S-cysteinylation were found to occur within hours at room temperature and days at −20 °C. Methionine oxidation of apoA-I took place on a longer time scale, setting in after albumin oxidation reached a plateau. Freeze–thaw cycles had a minimal effect on protein oxidation. In matched collections, protein oxidation in serum was the same as that in plasma. Albumin and apoA-I oxidation were not affected by sample headspace or the degree to which vials were sealed. ApoA-I, however, was unexpectedly found to oxidize faster in samples with lower surface-area-to-volume ratios. An initial survey of samples from patients with inflammatory conditions normally associated with elevated oxidative stress-including acute myocardial infarction and prostate cancer—demonstrated a lack of detectable apoA-I oxidation. Albumin S-cysteinylation in these samples was consistent with known but relatively brief exposures to temperatures above −30 °C (the freezing point of blood plasma). Given their properties and ease of analysis, these oxidized proteoforms, once fully validated, may represent the first markers of blood plasma specimen integrity based on direct measurement of oxidative molecular damage that can occur under suboptimal storage conditions.

Background: To determine the effects of high sucrose diets on vascular reactivity. We hypothesized that similar to high fat diets (HFD), HSD feeding would lead to increased adiposity resulting in inflammation and oxidative stress-mediated impairment of vasodilation.

Methods: Male Sprague-Dawley rats were fed control chow (Chow), HSD or HFD diets for 6 weeks. The role of inflammation and oxidative stress on impaired vasodilation were assessed in isolated mesenteric arterioles.

Results: HSD and HFD induced increased adiposity, oxidative stress and inflammation. HFD rats developed fasting hyperglycemia. Both HSD and HFD rats developed impaired glucose tolerance and hyperleptinemia. Nitric oxide (NO)-mediated vasodilation was significantly attenuated in both HSD and HFD rats but was normalized by treatment with antioxidants or anti-inflammatory drugs. Endothelial NO synthase (eNOS) protein expression was not affected by diet. Sensitivity to NO was reduced since NOS inhibition attenuated vasodilation in Chow rats but did not further impair vasodilation in HSD or HFD rats. Likewise, responsiveness to a NO donor was attenuated in both experimental groups.

Conclusions: Oxidative stress diminishes vasodilatory responsiveness in HSD and HFD rats through ROS-mediated scavenging of NO and decreased smooth muscle sensitivity to NO. Inflammation also plays a significant role in the impaired vasodilation.

Background: The National Health Interview Survey (NHIS) was used to ascertain whether increases in inadequate sleep differentially affected black and white Americans. We tested the hypothesis that prevalence estimates of inadequate sleep were consistently greater among blacks, and that temporal changes have affected these two strata differentially.

Methods: NHIS is an ongoing cross-sectional study of non-institutionalized US adults (≥18 years) providing socio-demographic, health risk, and medical factors. Sleep duration was coded as very short sleep [VSS] (<5 h), short sleep [SS] (5–6 h), or long sleep [LS] (>8 h), referenced to 7–8 h sleepers. Analyses adjusted for NHIS’ complex sampling design using SAS-callable SUDAAN.

Results: Among whites, the prevalence of VSS increased by 53 % (1.5 % to 2.3 %) from 1977 to 2009 and the prevalence of SS increased by 32 % (19.3 % to 25.4 %); prevalence of LS decreased by 30 % (11.2 % to 7.8 %). Among blacks, the prevalence of VSS increased by 21 % (3.3 % to 4.0 %) and the prevalence of SS increased by 37 % (24.6 % to 33.7 %); prevalence of LS decreased by 42 % (16.1 % to 9.4 %). Adjusted multinomial regression analysis showed that odds of reporting inadequate sleep for whites were: VSS (OR = 1.40, 95 % CI = 1.13-1.74, p < 0.001), SS (OR = 1.34, 95 % CI = 1.25-1.44, p < 0.001), and LS (OR = 0.94, 95 % CI = 0.85-1.05, NS). For blacks, estimates were: VSS (OR = 0.83, 95 % CI = 0.60-1.40, NS), SS (OR = 1.21, 95 % CI = 1.05-1.50, p < 0.001), and LS (OR = 0.84, 95 % CI = 0.64-1.08, NS).

Conclusions: Blacks and whites are characteristically different regarding the prevalence of inadequate sleep over the years. Temporal changes in estimates of inadequate sleep seem dependent upon individuals’ race/ethnicity.

Objective: To assess the informational, educational and instrumental environments among Mexican healthcare settings for their potential to promote physical activity (PA).

Materials and Methods: The Environmental Physical Activity Assessment Tool for Healthcare Settings (EPATHS) was developed to assess the PA environments of 40 clinics/hospitals representing the three Mexican healthcare systems in Guadalajara. The EPATHS assessed the presence and quality of PA enhancing features in the informational (e.g. signage),educational (e.g. pamphlets), and instrumental (e.g. stairs)environments of included clinics/hospitals.

Results: 28 (70%) clinics/hospitals had more than one floor with stairs; 60% of these had elevators. Nearly 90% of stairs were visible, accessible and clean compared to fewer than 30% of elevators. Outdoor spaces were observed in just over half (55%) of clinics/hospitals, and most (70%) were of good quality. Only 25% clinics/hospitals had educational PA materials.

Conclusions: The PA instrumental environment of Mexican healthcare settings is encouraging. The informational and educational environments could improve.

Depression and anxiety after stroke negatively affect patient outcomes; however, health care professionals may overlook poststroke depression and anxiety while they focus on the physical disabilities of patients soon after a stroke. The purpose of this study was to investigate the prevalence and predictors of depression, anxiety, or both concurrently at one month after stroke. We conducted a cross-sectional, descriptive study in a sample of 231 hospitalized patients with ischemic stroke in Korea. Data were collected by interviews using a series of structured questionnaires in addition to clinical data retrieved from patients’ medical records. More than 70% were identified as depressed, 45.9% experienced anxiety, and 43.7% had concurrent depression and anxiety. Using a multiple logistic regression analysis, we identified anxiety as a predictor of depression; depression as a predictor of anxiety; and female sex, headaches, and swallowing difficulty as predictors of the comorbidity of depression and anxiety. Periodical screenings for poststroke depression and anxiety from an early stage in a hospital to years after stroke in a community are recommended to provide better chances for early identification of patients at risk because depression and anxiety may manifest at any stage of recovery. Special attention should be given to individuals with culture-bound somatic symptoms in addition to female patients and those who have difficulty swallowing among Korean stroke patients.

Purpose: To identify barriers and discuss strategies for recruitment of older Chinese immigrants into clinical research studies.

Methods: A systematic review was conducted using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). PubMed, WEB of Science, CINAHL Plus, and the Cochrane Central Register of Controlled Trials were searched from 2001 to 2014. Empirical studies with Chinese immigrants aged 60 or older were identified and analyzed. Numerical analysis, such as calculation of response rates as indexes for recruitment outcomes, was conducted. Content analyses for recruitment barriers were abstracted.

Results: Thirteen studies of 4753 subjects were analyzed. Response rates ranged from 39% to 99%. Recruitment barriers include younger old age (i.e., 60-70 years old), low health literacy, longer length of stay in the US, limited English speaking ability, low acculturation, time constraints, inadequate transportation, social stigma about diseases, and mistrust of researchers.

Discussion: Recruitment can be facilitated by overcoming the aforementioned barriers, which include the following strategies: 1) using convenience sampling methods, particularly personal referral; 2) using special techniques to recruit younger subgroup of Chinese elders, such as doing outreach on holidays or weekends; 3) communicating effectively using participants’ native language; 4) exercising cultural competency; 5) establishing relationships of trust with participants and community leaders; 6) answering misconceptions about clinical trials; 7) providing incentives for participation; and 8) proper selection of research and interview locations.

The aim of this study was to evaluate the effects of moderate aerobic exercise training on sleep, depression, cortisol, and markers of immune function in patients with chronic primary insomnia. Twenty-one sedentary participants (16 women aged 44.7 ± 9 years) with chronic primary insomnia completed a 4-month intervention of moderate aerobic exercise. Compared with baseline, polysomnographic data showed improvements following exercise training. Also observed were reductions in depression symptoms and plasma cortisol. Immunologic assays revealed a significant increase in plasma apolipoprotein A (140.9 ± 22 to 151.2 ± 22 mg/dL) and decreases in CD4 (915.6 ± 361 to 789.6 ± 310 mm[superscript 3]) and CD8 (532.4 ± 259 to 435.7 ± 204 mm[superscript 3]). Decreases in cortisol were significantly correlated with increases in total sleep time (r = -0.51) and REM sleep (r = -0.52). In summary, long-term moderate aerobic exercise training improved sleep, reduced depression and cortisol, and promoted significant changes in immunologic variables.

Background: Success in asthma management hinges on patients’ competency to detect and respond to ever-changing symptom severity. Thus, it is crucial to have reliable, simple, and sustainable methods of symptom monitoring that can be readily incorporated into daily life. Although visual analogue scale (VAS) has been considered as a simple symptom assessment method, its utility as a daily symptom monitoring tool in adolescents is unknown. This study was to determine the concurrent validity of VAS in capturing diurnal changes in symptoms and to examine the relationships between VAS and asthma control and pulmonary function.

Methods: Forty-two adolescents (12-17 years old) with asthma completed daily assessment of symptoms twice per day, morning and bedtime, for a week using VAS and 6-item symptom diary concurrently. Asthma control was measured at enrollment and 6 month later, and spirometry was conducted at enrollment. Pearson correlations, multilevel modeling and regression were conducted to assess the relationships between VAS and symptom diary, asthma control and FEV1.

Results: Morning and evening VAS was positively associated with symptom diary items of each corresponding time frame of the day (r = 0.41–0.58, p < 0.0001). Morning VAS was significantly predicted by morning diary data reflecting nocturnal wakening (β = 2.13, p = 0.033) and morning symptoms (β = 4.09, p = 0.002), accounting for 57% of the total variance of morning VAS. Similarly, changes in four evening diary items, particularly shortness of breath (β = 2.60, p = 0.028), significantly predicted changes in evening VAS, accounting for 55% of the total variance. Average VAS scores correlated with asthma control (r = 0.65, p < 0.001) and FEV1 (r = −0.38, p = 0.029), and were predictive of asthma control 6 months later (β = 0.085, p = 0.006).

Conclusions: VAS is a valid tool capturing diurnal changes in symptoms reflected in a multi-item symptom diary. Moreover, VAS is a valid measure predicting concurrent and future asthma control. The findings suggest VAS can be a simple alternative to daily dairies for daily symptom monitoring, which can provide invaluable information about current and future asthma control without substantially increasing self-monitoring burdens for adolescent patients.

Introduction: Individuals with osteoarthritis (OA) show increased morbidity and mortality. Telomere length, a measure of cellular aging, predicts increased morbidity and mortality. Telomeres shorten with persisting biological and psychosocial stress. Living with chronic OA pain is stressful. Previous research exploring telomere length in people with OA has produced inconsistent results. Considering pain severity may clarify the relationship between OA and telomeres.

Objectives: We hypothesized that individuals with high OA chronic pain severity would have shorter telomeres than those with no or low chronic pain severity.

Methods: One hundred thirty-six adults, ages 45 to 85 years old, with and without symptomatic knee OA were included in the analysis. Peripheral blood leukocyte telomere length was measured, and demographic, clinical, and functional data were collected. Participants were categorized into 5 pain severity groups based on an additive index of frequency, intensity, time or duration, and total number of pain sites (FITT). Covariates included age, sex, race or ethnicity, study site, and knee pain status.

Results: The no or low chronic pain severity group had significantly longer telomeres compared with the high pain severity group, P50.025. A significant chronic pain severity dose response emerged for telomere length, P50.034. The FITT chronic pain severity index was highly correlated with the clinical and functional OA pain measures. However, individual clinical and functional measures were not associated with telomere length.

Conclusion: Results demonstrate accelerated cellular aging with high knee OA chronic pain severity and provide evidence for the potential utility of the FITT chronic pain severity index in capturing the biological burden of chronic pain.

Background: The cytokine MIF (Macrophage Migration Inhibitory Factor) has diverse physiological roles and is present at elevated concentrations in numerous disease states. However, its molecular heterogeneity has not been previously investigated in biological samples. Mass Spectrometric Immunoassay (MSIA) may help elucidate MIF post-translational modifications existing in vivo and provide additional clarity regarding its relationship to diverse pathologies.

Results: In this work, we have developed and validated a fully quantitative MSIA assay for MIF, and used it in the discovery and quantification of different proteoforms of MIF in serum samples, including cysteinylated and glycated MIF. The MSIA assay had a linear range of 1.56-50 ng/mL, and exhibited good precision, linearity, and recovery characteristics. The new assay was applied to a small cohort of human serum samples, and benchmarked against an MIF ELISA assay.

Conclusions: The quantitative MIF MSIA assay provides a sensitive, precise and high throughput method to delineate and quantify MIF proteoforms in biological samples.