Transcriptomic analysis of hidradenitis suppurativa skin suggests roles for multiple inflammatory pathways in disease pathogenesis.

OBJECTIVE: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with limited treatment options; therefore, the current study investigated the downstream signaling pathways that are differentially expressed in HS subjects and may drive disease pathogenesis. METHODS: The expression of 144 genes was evaluated in the skin of 16 healthy subjects and 34 subjects with mild to severe HS using QuantiGene Plex assay. RESULTS: One hundred and twenty-nine genes were significantly elevated in lesional HS skin as compared to the skin of healthy controls including pro-inflammatory cytokines (IL-1α, IL-6, TNF-α), IL-17-associated cytokines (IL-17A, IL-17F, IL-23A), the IL-10 family of cytokines (IL-10, IL-19, IL-20, IL-22, IL-24), and IFN family members (IFNA1, IFNB1, IFNG, IL-12B). This corresponded with increased expression of tyrosine kinases (JAK1, JAK3, BTK, SYK) and their downstream signaling partners (STAT1, STAT2, STAT3, STAT5A, STAT5B, STAT6). CONCLUSION: These data illustrate the diverse immune activation in lesional HS skin and suggest that deeper interrogation of the disease heterogeneity may reveal unique opportunities for targeted therapies in designated subpopulations.

Galectin-3 as a Predictor of Long-term Survival After Isolated Coronary Artery Bypass Grafting Surgery.

BACKGROUND: Galectin-3 (Gal-3) is a well-established biomarker of adverse clinical outcomes, but its prognostic value for long-term survival after cardiac surgery is not well understood. Elevated levels of Gal-3 have been found to be remarkably associated with higher risk of death in both acute decompensated and chronic heart failure populations. Its prognostic value for long-term survival after cardiac surgery is not known. METHODS: A sample of patients contributing to the Northern New England Cardiovascular Disease Study Group Cardiac Surgery Registry from 2004 to 2007 were enrolled in a prospective biomarker cohort (N = 1690). Preoperative Gal-3 levels were measured and categorized by quartile. We used Kaplan-Meier survival analysis and Cox regression models, adjusting for variables in The Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategy probability calculator to evaluate the association between elevated Gal-3 levels and survival to 6 years. RESULTS: Preoperative Gal-3 levels ranged from 1.72 to 28.89 ng/mL (mean, 8.96 ng/mL; median, 8.06 ng/mL; interquartile range, 5.42-11.08 ng/mL). Crude survival decreased by increasing quartile. After adjustment, serum levels of Gal-3 in the highest quartile of the cohort were associated with significantly decreased survival compared with the lowest quartile (hazard ratio [HR] 2.22; 95% confidence interval [CI], 1.40-3.54; P = .001). No decrease in survival was found for the middle quartiles (HR 1.36; 95% CI, 0.87-2.12; P = .177). CONCLUSIONS: A substantial association was found between elevated preoperative Gal-3 levels and risk of mortality after isolated coronary artery bypass grafting surgery. An assessment of the relationship between preoperative serum biomarkers and long-term survival can be used for risk stratification or estimating postsurgical prognosis.

The Association between Cytokines and 365-Day Readmission or Mortality in Adult Cardiac Surgery.

Cardiac surgery results in a multifactorial systemic inflammatory response with inflammatory cytokines, such as interleukin-10 and 6 (IL-10 and IL-6), shown to have potential in the prediction of adverse outcomes including readmission or mortality. This study sought to measure the association between IL-6 and IL-10 levels and 1-year hospital readmission or mortality following cardiac surgery. Plasma biomarkers IL-6 and IL-10 were measured in 1,047 patients discharged alive after isolated coronary artery bypass graft surgery from eight medical centers participating in the Northern New England Cardiovascular Disease Study Group between 2004 and 2007. Readmission status and mortality were ascertained using Medicare, state all-payer claims, and the National Death Index. We evaluated the association between preoperative and postoperative cytokines and 1-year readmission or mortality using Kaplan-Meier estimates and Cox's proportional hazards modeling, adjusting for covariates used in the Society of Thoracic Surgeons 30-day readmission model. The median follow-up time was 1 year. After adjustment, patients in the highest tertile of postoperative IL-6 values had a significantly increased risk of readmission or death within 1 year (HR: 1.38; 95% CI: 1.03-1.85), and an increased risk of death within 1 year of discharge (HR: 4.88; 95% CI: 1.26-18.85) compared with patients in the lowest tertile. However, postoperative IL-10 levels, although increasing through tertiles, were not found to be significantly associated independently with 1-year readmission or mortality (HR: 1.25; 95% CI: .93-1.69). Pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10 may be postoperative markers of cardiac injury, and IL-6, specifically, shows promise in predicting readmission and mortality following cardiac surgery.

The Association Between Novel Biomarkers and 1-Year Readmission or Mortality After Cardiac Surgery.

BACKGROUND: Novel cardiac biomarkers including soluble suppression of tumorigenicity 2, galectin-3, and the N-terminal prohormone of brain natriuretic peptide may be associated with long-term adverse outcomes after cardiac surgery. We sought to measure the association between cardiac biomarker levels and 1-year hospital readmission or mortality. METHODS: Plasma biomarkers from 1,047 patients discharged alive after isolated coronary artery bypass graft surgery from 8 medical centers were measured in a cohort from the Northern New England Cardiovascular Disease Study Group between 2004 and 2007. We evaluated the association between preoperative and postoperative biomarkers and 1-year readmission or mortality using Kaplan-Meier estimates and Cox proportional hazards modeling, adjusting for covariates used in The Society of Thoracic Surgeons 30-day readmission model. RESULTS: The median follow-up time was 365 days. After adjustment for established risk factors, above-median levels of postoperative galectin-3 (median 10.35 ng/mL; hazard ratio, 1.40; 95% confidence interval, 1.08 to 1.80; p = 0.010) and N-terminal prohormone of brain natriuretic peptide (median = 15.21 ng/mL, hazard ratio, 1.42; 95% confidence interval, 1.07 to 1.87; p = 0.014) were each significantly associated with 1-year readmission or mortality. CONCLUSIONS: In patients undergoing cardiac surgery, novel cardiac biomarkers were associated with readmission or mortality independent of established risk factors. Measurement of these biomarkers may improve our ability to identify patients at highest risk for readmission or mortality before discharge. This will also allow resource allocation accordingly, while implementing strategies for personalized medicine based on the biomarker profile of the patient.

An Exploration of Shift Work, Fatigue, and Gender Among Police Officers: The BCOPS Study.

The present study examined the association between shift work and fatigue among male ( n = 230) and female ( n = 78) police officers. A 15-year work history database was used to define dominant shifts as day, afternoon, or night. A 10-item questionnaire created from the Standard Shiftwork Index (SSI) assessed fatigue. Gender-stratified analyses of variance and covariance and Poisson regression were used to compare means and prevalence of individual items across shifts. No significant differences in total fatigue scores were observed across shifts. However, the prevalence of the fatigue item "feelings of tiredness" was 89% higher among male officers working the afternoon shift compared with officers working the day shift (prevalence ratio [PR] = 1.89, 95% confidence interval [CI] = [1.12, 3.23], p = .020), after adjustment for covariates. Women reported a lower prevalence of tiredness than men on the afternoon shift. Organizations with afternoon shift workers should consider reducing fatigue at work through education and other methods.

The association between nonmedical use of prescription drugs and extreme weight control behavior among adolescents.

Although extreme weight control behavior (EWCB) is associated with substance use, no research has examined the association between the nonmedical use of prescription drugs (NMUPD) and EWCB. Self-report data were collected from a sample of 4,148 students in Grades 9-12 enrolled in 5 high schools across the United States. Logistic regression models were constructed to examine the nonmedical use of prescription pain relievers, depressants, stimulants, and a composite measure for any NMUPD, and the EWCB of fasting, use of diet pills, powders, or liquids, and vomiting or laxative use. Models were estimated before and after controlling for key covariates for males and females. Approximately 16% of respondents reported any EWCB during the past 30 days, while 11% reported any NMUPD during the past 30 days. After covariate adjustment, any NMUPD was associated with any EWCB in both males and females (p < .05), and all EWCB remained significant in females who reported prescription pain reliever use (p < .01), with 2 out of 3 remaining significant for prescription stimulant and depressant use (p < .01). The only significant association detected for males was between prescription pain reliever use and using diet pills, powders, or liquids (OR = 2.2, p < .01). Results suggest significant associations between NMUPD and EWCB, with variations by sex. These findings provide directions for additional research and point to several potential identification and intervention efforts. (PsycINFO Database Record

Association Between Discrimination and Objective and Subjective Sleep Measures in the Midlife in the United States Study Adult Sample.

OBJECTIVE: Evidence suggests that sleep quality is worse in nonwhite minorities compared with whites. Poor sleep is associated with higher levels of perceived interpersonal discrimination, which is consistently reported among minorities. However, the literature is limited in exploring discrimination with both objective and subjective sleep outcomes in the same sample. We examined the relationship between discrimination and markers of subjective and objective sleep in a racially diverse sample. METHODS: The analytic sample included 441 participants of the Midlife in the United States II (MIDUS) study (M [SD] age, 46.6 [1.03]; female, 57.9%; male, 42.1%; nonwhite, 31.7%). Complete data were available for 361 participants. Sleep measures included the Pittsburgh Sleep Quality Index, sleep latency, wake after sleep onset, and sleep efficiency derived from 7-day actigraphy. Discrimination was measured with the Williams Everyday Discrimination Scale. Ordinary least squares and logistic regression models were used to assess the relationship between discrimination and the subjective and objective measures of sleep. RESULTS: After adjusting for covariates, respondents with higher discrimination scores were significantly more likely to experience poor sleep efficiency (odds ratio, 1.12; p = .005) and report poorer sleep quality (odds ratio, 1.09; p = .029) on the basis of the Pittsburgh Sleep Quality Index. Higher discrimination scores were also associated with longer wake after sleep onset (b = 0.032, p < .01) and more sleep difficulties (b = 0.049, p = .01). Discrimination attenuated all differences in the sleep measures between whites and nonwhites except for sleep efficiency. CONCLUSIONS: The findings support the model that discrimination acts as a stressor that can disrupt subjective and objective sleep. These results suggest that interpersonal discrimination explains some variance in worse sleep among nonwhites compared with whites.

Specific domains of Aß facilitate aggregation on and association with lipid bilayers.

A hallmark of Alzheimer's disease, a late-onset neurodegenerative disease, is the deposition of neuritic amyloid plaques composed of aggregated forms of the ß-amyloid peptide (Aß). Aß forms a variety of nanoscale, toxic aggregate species ranging from small oligomers to fibrils. Aß and many of its aggregate forms strongly interact with lipid membranes, which may represent an important step in several toxic mechanisms. Understanding the role that specific regions of Aß play in regulating its aggregation and interaction with lipid membranes may provide insights into the fundamental interaction between Aß and cellular surfaces. We investigated the interaction and aggregation of several Aß fragments (Aß1-11, Aß1-28, Aß10-26, Aß12-24, Aß16-22, Aß22-35, and Aß1-40) in the presence of supported model total brain lipid extract (TBLE) bilayers. These fragments represent a variety of chemically unique domains within Aß, that is, the extracellular domain, the central hydrophobic core, and the transmembrane domain. Using scanning probe techniques, we elucidated aggregate morphologies for these different Aß fragments in free solution and in the presence of TBLE bilayers. These fragments formed a variety of oligomeric and fibrillar aggregates under free solution conditions. Exposure to TBLE bilayers resulted in distinct aggregate morphologies compared to free solution and changes in bilayer stability dependent on the Aß sequence. Aß10-26, Aß16-22, Aß22-35, and Aß1-40 aggregated into a variety of distinct fibrillar aggregates and disrupted the bilayer structure, resulting in altered mechanical properties of the bilayer. Aß1-11, Aß1-28, and Aß12-24 had minimal interaction with lipid membranes, forming only sparse oligomers.