Stress Reactivity as a Contributor to Racial and Socioeconomic Disparities: Rationale and Baseline Results From the Richmond Stress and Sugar Study.

OBJECTIVE: There are pronounced racial and socioeconomic disparities in type 2 diabetes. Although "stress" as a general phenomenon is hypothesized to contribute to these disparities, few studies have objective measures of stress reactivity in diverse samples to test hypotheses about purported mechanisms. This study describes the rationale and baseline characteristics of a cohort designed to address the question: how does stress contribute to disparities in diabetes risk? METHODS: The Richmond Stress and Sugar Study recruited 125 adults at elevated risk of type 2 diabetes using a two-by-two sampling frame wherein non-Hispanic whites and African Americans (AAs) were each recruited from neighborhoods of higher and lower socioeconomic status (SES). Stress reactivity was assessed using the Trier Social Stress Test (TSST) and salivary cortisol. Analyses of variance and multilevel modeling were used to examine how stress reactivity varied both within and across race and neighborhood SES. RESULTS: The mean (SD) age was 57.4 (7.3) years, 49% were female, 54% were AA or another racial/ethnic minority, and mean hemoglobin A1c level was in the prediabetes range (5.8%; range, 5.50%-5.93%). Living in a lower-SES neighborhood was associated with 16% (95% confidence interval [CI] = -0.04 to 34) higher pre-TSST cortisol, 8.4% (95% CI = -14 to -3) shallower increase in response to the TSST, and 1% (95% CI = 0.3 to 1.7) steeper decline post-TSST than living in the higher neighborhood SES. Post-TSST cortisol decline was 3% greater among AA compared with non-Hispanic whites. Race-by-SES interaction terms were generally small and nonsignificant. CONCLUSIONS: SES is associated with stress reactivity among adults at high risk of diabetes.

Promoting sustained diabetes management: Identifying challenges and opportunities in developing an alumni peer support component of the YMCA Diabetes Control Program.

OBJECTIVE: To explore the perspectives of coaches and participant alumni of the YMCA Diabetes Control Program (DCP) to inform the development of a peer support component of the DCP for sustained diabetes self-management. METHODS: Coaches (n = 2) and alumni (n = 38) participated in semi-structured interviews and focus groups regarding their experiences with the DCP and anticipated challenges and strengths of incorporating alumni peer support into the program. Transcripts were analyzed using content analysis to identify topics related to peer support. RESULTS: Six topics emerged related to strengths and weaknesses of the coach and peer roles, including how those roles influenced motivation and accountability in self-management. Both roles provide encouragement for sustained behavior change, particularly in the face of setbacks. Interest in becoming an alumni peer supporter was strongly related to a sense of reciprocity and potential for mutual benefit, while concerns centered on unclear expectations and a desire for formal training. CONCLUSION: Program alumni saw value in continued formal contact not only with their coaches, but with fellow peers, as part of their sustained diabetes self-management and anticipated reciprocal benefits. PRACTICE IMPLICATIONS: Findings illustrate opportunities for, and the value of, incorporating alumni peer support into hierarchical coach-led diabetes self-management programs.

Chemotactic activity of S100A7 (Psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15.

Human S100A7 (psoriasin) is overexpressed in inflammatory diseases. The recently discovered, co-evolved hS100A15 is almost identical in sequence and up-regulated with hS100A7 during cutaneous inflammation. The functional role of these closely related proteins for inflammation remains undefined. By generating specific Abs, we demonstrate that hS100A7 and hS100A15 proteins are differentially expressed by specific cell types in the skin. Although highly homologous, both proteins are chemoattractants with distinct chemotactic activity for leukocyte subsets. We define RAGE (receptor for advanced glycation end products) as the hS100A7 receptor, whereas hS100A15 functions through a Gi protein-coupled receptor. hS100A7-RAGE binding, signaling, and chemotaxis are zinc-dependent in vitro, reflecting the previously reported zinc-mediated changes in the hS100A7 dimer structure. When combined, hS100A7 and hS100A15 potentiate inflammation in vivo. Thus, proinflammatory synergism in disease may be driven by the diverse biology of these almost identical proteins that have just recently evolved. The identified S100A7 interaction with RAGE may provide a novel therapeutic target for inflammation.

Gene from a psoriasis susceptibility locus primes the skin for inflammation.

Psoriasis is a common complex genetic disease characterized by hyperplasia and inflammation in the skin; however, the relative contributions of epidermal cells and the immune system to disease pathogenesis remain unclear. Linkage studies have defined a psoriasis susceptibility locus (PSORS4) on 1q21, the epidermal differentiation complex, which includes genes for small S100 calcium-binding proteins. These proteins are involved in extracellular and intracellular signaling during epithelial host defense, linking innate and adaptive immunity. Inflammation-prone psoriatic skin constitutively expresses elevated concentrations of S100A7 (psoriasin) and S100A15 (koebnerisin) in the epidermis. Here, we report that genetically modified mice expressing elevated amounts of doxycycline-regulated mS100a7a15 in skin keratinocytes demonstrated an exaggerated inflammatory response when challenged by exogenous stimuli such as abrasion (Koebner phenomenon). This immune response was characterized by immune cell infiltration and elevated concentrations of T helper 1 (T(H)1) and T(H)17 proinflammatory cytokines, which have been linked to the pathogenesis of psoriasis and were further amplified upon challenge. Both inflammation priming and amplification required mS100a7a15 binding to the receptor of advanced glycation end products (RAGE). mS100a7a15 potentiated inflammation by acting directly as a chemoattractant for leukocytes, further increasing the number of inflammatory cells infiltrating the skin. This study provides a pathogenetic psoriasis model using a psoriasis candidate gene to link the epidermis and innate immune system in inflammation priming, highlighting the S100A7A15-RAGE axis as a potential therapeutic target.

Highly homologous hS100A15 and hS100A7 proteins are distinctly expressed in normal breast tissue and breast cancer.

Human S100A7 (psoriasin) is considered a marker for specific stages of breast cancer. hS100A15 is almost identical to hS100A7 and difficult to discriminate. We developed specific probes to distinguish hS100A7 and hS100A15, and demonstrate their differential distribution in normal breast tissue. Further, hS100A7 and S100A15 transcripts are elevated in ER/PR negative breast cancers, but hS100A15 protein is detected in all cancer specimens while hS100A7 protein is sporadically expressed. The differential regulation, expression and distribution of hS100A7 and hS100A15 and their reported distinct functions are compelling reasons to discriminate among these proteins in normal breast and breast cancers.

Diffusion-weighted imaging of inflammatory myopathies: polymyositis and dermatomyositis.

Muscles of myositis patients examined with MRI demonstrate heterogeneous pathology ranging from unaffected muscle groups to severe inflammation, fat infiltration, and eventually, more serious fat replacement. The purpose of this investigation was to characterize myositic thigh muscles using diffusion-weighted imaging (DWI) and to examine fluid motion at various disease stages. We chose to characterize total fluid motion within the muscle using the model proposed by Le Bihan et al (6,7) in which the apparent diffusion coefficient (ADC), diffusion in the extra- and intracellular muscle compartments (D), perfusion in capillaries (pseudodiffusion) (D*), and volume fraction of capillary perfusion (f) are determined. Unaffected patient muscles have DWI coefficients equivalent to those of normal muscles. Inflamed muscles show elevated ADC and D values compared to normal muscles (P < 0.0005), and fat-infiltrated muscles have lower values than control muscles (P < 0.001). Inflamed muscles have lower f values than unaffected muscles (P < 0.009), suggesting decreased fractional volume of capillary perfusion. DWI provides quantitative data on molecular fluid motion in diseased muscles and affords the potential for longitudinal monitoring of myositic patients.