Changes in working memory performance in youth following concussion.

OBJECTIVE: The purpose of this study was to compare the working memory (WM) performance pre- and post-concussion, and investigate the relationships between performance changes and characteristics such as self-reported symptom scores, number of days post-injury and age at injury in 10-14-year-old youth. METHODS: Twenty-one youth (17 males) aged 10-14 years recruited from the community completed verbal and non-verbal WM tasks pre- and post-concussion. Performance was measured using accuracy and performance errors (false alarms and misses). Pre- and post-tests were compared using a Wilcoxon signed rank test, and effect size was determined using matched-pairs rank biserial correlation. RESULTS: Comparisons showed lower verbal WM accuracy at post-test, greater verbal and non-verbal WM false alarm errors at post-test, and greater verbal WM miss errors at post-test (all r ≥ 0.30). Correlations between performance and characteristics revealed associations between younger youth and lower non-verbal WM accuracy and more false alarms at post-test, as well as an association among non-verbal WM miss errors, higher PCS scores and fewer days since injury at post-test. CONCLUSIONS: The current study found lower WM performance in youth following concussion. Furthermore, the findings suggest that false alarm errors may be a useful screening measure acutely post-concussion when assessing WM performance in youth.

Significance of chronic tachycardia in systemic lupus erythematosus.

OBJECTIVE: A significant subset of systemic lupus erythematosus (SLE) patients exhibit chronic tachycardia (CT) of unknown significance. We postulated that CT is a marker of lupus activity and severity. METHODS: A cross-sectional database at the University of Chicago recorded disease activity, damage, disease manifestations, pain, anxiety, and physical function (PF). CT was defined as a heart rate of ≥95 beats per minute in at least 3 out of 4 sequential visits. Demographic, disease-specific, and self-reported symptoms were compared between groups with and without tachycardia. RESULTS: Of the 243 subjects analyzed, 14.8% had CT. On univariate analysis, CT was associated with younger age at the time of enrollment (P = 0.004), number of hospitalizations adjusted for years of SLE (P = 0.001), current prednisone dose (P < 0.0001), history of serositis (P = 0.03), anxiety score (P = 0.004), and poor PF (P = 0.0017). All domains of the Short Form 36 (SF-36) health survey correlated strongly with CT, but on multivariate regression this correlation appeared to be driven by poor PF. On multivariate regression, the Systemic Lupus Erythematosus Disease Activity Index score (P = 0.03), younger age (P = 0.04), and poor PF by the SF-36 domain (P = 0.006) were independently correlated with CT, and anxiety trait and hemoglobin both trended closely to significant association (P = 0.08 for both). CONCLUSION: CT is prevalent in SLE and is a clinically relevant physical finding. It implies greater lupus activity and physical frailty. Univariate association with serositis raises the possibility of subclinical serositis or pancarditis. Further study to elucidate the cardiopulmonary status of SLE patients with unexplained CT is planned.

Correlates of sleep abnormalities in systemic lupus: a cross-sectional survey in an urban, academic center.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is associated with poor health-related quality-of-life outcomes. OBJECTIVES: The objectives of this study were to identify correlates of the domains of the Medical Outcomes Study (MOS) Sleep Scale in SLE and to determine the factors most associated with overall sleep quality. METHODS: Sleep in 118 SLE patients was assessed using the self-administered MOS Sleep Scale. Bivariate correlations were determined between each of 6 MOS Sleep subscale scores and each sociodemographic, clinical, or psychological predictor variable. Serial hierarchical multiple regression analyses were computed to identify the variables associated with the individual sleep domains and the overall Sleep Problems Index. RESULTS: The MOS Sleep Scale scores of patients with SLE were poorer than the US general population. Depression moderately correlated with 5 (all P < 0.01) and anxiety with 4 subscale scores (all P < 0.05). The SLE Disease Activity Index did not significantly correlate with any of the subscale scores. Results of a multivariate regression model showed that sleep adequacy and sleep disturbance were independently associated with depression (ß = -0.84; 95% confidence interval [CI], -1.37 to -0.32; and ß = 0.80; 95% CI, 0.15-1.45; respectively). Daytime somnolence was significantly associated with daily prednisone dosage (ß = 0.54; 95% CI, 0.29-0.80) and anxiety trait (ß = 0.81; 95% CI, 0.41-1.21). Snoring independently correlated with anxiety (ß = 1.64; 95% CI, 0.80-2.29). When demographic, clinical, and psychological variables were simultaneously regressed on the Sleep Problems Index, pain trended toward association with overall sleep problems (ß = 0.17; 95% CI, -0.02 to 0.36). CONCLUSIONS: Patients with SLE have greater sleep problems relative to the general population. Psychosocial factors, particularly depression and anxiety, are important determinants that are significantly associated with sleep abnormalities in SLE.

A study of racial/ethnic differences in treatment preferences among lupus patients.

OBJECTIVES: To determine whether there are racial/ethnic differences in the willingness of SLE patients to receive CYC or participate in clinical trials, and whether demographic, psychosocial and clinical characteristics contribute to these differences. METHODS: Data from 120 African-American and 62 white lupus patients were evaluated. Structured telephone interviews were conducted to determine treatment preferences, as well as to study characteristics and beliefs that may affect these preferences. Data were analysed using serial hierarchical multivariate logistic regression and deviances were calculated from a saturated model. RESULTS: Compared with their white counterparts, African-American SLE patients expressed less willingness to receive CYC (67.0% vs 84.9%, P = 0.02) if their lupus worsened. This racial/ethnic difference remained significant after adjusting for socioeconomic and psychosocial variables. Logistic regression analysis showed that African-American race [odds ratio (OR) 0.29, 95% CI 0.10, 0.80], physician trust (OR 1.05, 95% CI 1.00, 1.12) and perception of treatment effectiveness (OR 1.40, 95% CI 1.22, 1.61) were the most significant determinants of willingness to receive CYC. A trend in difference by race/ethnicity was also observed in willingness to participate in a clinical trial, but this difference was not significant. CONCLUSION: This study demonstrated reduced likelihood of accepting CYC in African-American lupus patients compared with white lupus patients. This racial/ethnic variation was associated with belief in medication effectiveness and trust in the medical provider, suggesting that education about therapy and improved trust can influence decision-making among SLE patients.

Osteopontin alleles are associated with clinical characteristics in systemic lupus erythematosus.

Variants of the osteopontin (OPN) gene have been associated with systemic lupus erythematosus (SLE) susceptibility and cytokine profiles in SLE patients. It is not known whether these alleles are associated with specific clinical phenotypes in SLE. We studied 252 well-characterized SLE patients from a multiethnic cohort, genotyping the rs11730582, rs28357094, rs6532040, and rs9138 SNPs in the OPN gene. Ancestry informative markers were used to control for genetic ancestry. The SLE-risk allele rs9138C in the 3' UTR region was associated with photosensitivity in lupus patients across all ancestral backgrounds (meta-analysis OR = 3.2, 95% CI = 1.6-6.5, P = 1.0 × 10⁻³). Additionally, the promoter variant rs11730582C demonstrated suggestive evidence for association with two hematologic traits: thrombocytopenia (OR = 2.1, P = 0.023) and hemolytic anemia (OR = 2.6, P = 0.036). These clinical associations with SNPs in the promoter and 3' UTR regions align with previously reported SLE-susceptibility SNPs in OPN and suggest potential roles for these variants in antibody-mediated cytopenias and skin inflammation in SLE.

Toward enabling winter occupations: testing a winter coat designed for older adults.

BACKGROUND: Previous research indicates that older adults have difficulties using winter clothing, which contributes to their risk of isolation during winter. Research has also shown that a winter coat that requires less flexibility, strength, and dexterity would help support this population. PURPOSE: This pilot study evaluated the measured and perceived effectiveness of a winter coat prototype that had a funnel sleeve design. METHODS: Eight older adults trialed three coats (the participant's own coat, a coat fitted with sleeve gripper, and the prototype coat), which were evaluated though shoulder range of motion measurements and by the participant completing a survey. FINDINGS: Less shoulder range of motion was used to put on the prototype coat. Survey findings support range of motion data that Sleeve Gripper has limited utility. IMPLICATIONS: A funnel sleeve design may require less range of motion at the shoulder compared to other coats.

Network analysis of associations between serum interferon-α activity, autoantibodies, and clinical features in systemic lupus erythematosus.

OBJECTIVE: Interferon-α (IFNα) is a primary pathogenic factor in systemic lupus erythematosus (SLE), and high IFNα levels may be associated with particular clinical manifestations. The prevalence of individual clinical and serologic features differs significantly by ancestry. This study was undertaken to detect associations between clinical and serologic disease manifestations and serum IFNα activity in a large diverse SLE cohort, using multivariate and network analyses. METHODS: We studied 1,089 SLE patients (387 African American, 186 Hispanic American, and 516 European American patients). The presence or absence of individual American College of Rheumatology (ACR) clinical criteria for SLE, autoantibodies, and serum IFNα activity data were analyzed in univariate and multivariate models. Iterative multivariate logistic regression was performed in each ancestral background group separately to establish the network of associations between variables that were independently significant following Bonferroni correction. RESULTS: In all ancestral backgrounds, high IFNα activity was associated with anti-Ro and anti-double-stranded DNA antibodies (P = 4.6 × 10(-18) and P = 2.9 × 10(-16) , respectively). Younger age, non-European ancestry, and anti-RNP were also independently associated with increased serum IFNα activity (P ≤ 6.7 × 10(-4) ). We found 14 unique associations between variables in network analysis, and only 7 of these associations were shared among >1 ancestral background. Associations between clinical criteria were different for different ancestral backgrounds, while autoantibody-IFNα relationships were similar across backgrounds. IFNα activity and autoantibodies were not associated with ACR clinical features in multivariate models. CONCLUSION: Our findings indicate that serum IFNα activity is strongly and consistently associated with autoantibodies, and not independently associated with clinical features in SLE. IFNα may be more relevant to humoral tolerance and initial pathogenesis than later clinical disease manifestations.

Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice.

Vision loss affects >3 million Americans and many more people worldwide. Although predisposing genes have been identified their link to known environmental factors is unclear. In wild-type animals DNA alkylating agents induce photoreceptor apoptosis and severe retinal degeneration. Alkylation-induced retinal degeneration is totally suppressed in the absence of the DNA repair protein alkyladenine DNA glycosylase (Aag) in both differentiating and postmitotic retinas. Moreover, transgenic expression of Aag activity restores the alkylation sensitivity of photoreceptors in Aag null animals. Aag heterozygotes display an intermediate level of retinal degeneration, demonstrating haploinsufficiency and underscoring that Aag expression confers a dominant retinal degeneration phenotype.

DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice.

Chronic inflammation increases cancer risk. While it is clear that cell signaling elicited by inflammatory cytokines promotes tumor development, the impact of DNA damage production resulting from inflammation-associated reactive oxygen and nitrogen species (RONS) on tumor development has not been directly tested. RONS induce DNA damage that can be recognized by alkyladenine DNA glycosylase (Aag) to initiate base excision repair. Using a mouse model of episodic inflammatory bowel disease by repeated administration of dextran sulfate sodium in the drinking water, we show that Aag-mediated DNA repair prevents colonic epithelial damage and reduces the severity of dextran sulfate sodium-induced colon tumorigenesis. Importantly, DNA base lesions expected to be induced by RONS and recognized by Aag accumulated to higher levels in Aag-deficient animals following stimulation of colonic inflammation. Finally, as a test of the generality of this effect we show that Aag-deficient animals display more severe gastric lesions that are precursors of gastric cancer after chronic infection with Helicobacter pylori. These data demonstrate that the repair of DNA lesions formed by RONS during chronic inflammation is important for protection against colon carcinogenesis.