Background Fibromyalgia (FM) is a chronic condition characterized by diffused musculoskeletal pain and overwhelming fatigue. Purpose To compare the gene expression profiles of fatigued FM women with different levels of pain and catastrophizing. Methods Nine FM women enrolled in an active Medstar Research Institute protocol were included in the gene expression analyses of peripheral blood RNA using Affymetrix GeneChip® human genome U133 Plus 2.0 array. Scores from Brief Pain Inventory, Pain Catastrophizing Scale, and Multidimensional Fatigue Inventory categorized the 9 participants into pain (high, n = 3; low, n = 6) and catastrophizing groups (high, n = 5; low, n = 4). Discussion Differential expression of 107 genes between the high and low pain groups and 139 genes between the high and low catastrophizing groups (over 2.0-fold change, p < 0.05) were observed. Network analyses showed interferon signaling and interferon regulatory activation factor pathways distinguished between the pain groups while dendritic cell maturation delineated between the catastrophizing groups. Conclusion Findings provide preliminary evidence that specific physiological pathways may possibly delineate pain and catastrophizing mechanisms. Further investigation using larger and more homogenous sample is warranted.

Background Irritable bowel syndrome (IBS) is a serious health problem that affects an estimated 10–15% of people worldwide and has economic consequences in the United States of over $30 billion annually. In the US, IBS affects all races and both sexes, with more females than males (2 : 1) reporting symptoms consistent with IBS. Although the etiology of this functional gastrointestinal disorder is unknown, literature suggests that a subclinical inflammatory component has a role in the etiologic mechanisms underlying IBS. The aim of this study was to evaluate the gene expression of inflammatory biomarkers in patients with and without IBS and among different IBS phenotypes. Methods Irritable bowel syndrome patients (n = 12) that met Rome III Criteria for IBS longer than 6 months were compared with healthy matched controls (n = 12). Peripheral whole blood from fasting participants was collected and RNA was extracted. The expression of 96 inflammatory genes was then analyzed using a custom quantitative real-time PCR array. Key Results CCL-16 gene expression was upregulated by 7.46-fold in IBS patients when compared with controls. CCL-16 was overexpressed by over 130-fold in IBS-constipation patients when compared with both controls and IBS-diarrhea patients. Conclusions & Inferences These results further suggest a subclinical inflammatory component underlying IBS. To better understand the phenotypic differences in IBS it is important to broaden the study of these inflammatory and other biomarkers.

Background Research examining the role of stress in gastrointestinal (GI) symptoms such as chronic abdominal pain (CAP) is controversial. The purpose of this study was to examine the expression of genes involved in metabolic stress and toxicity in men and women with high and low levels of perceived stress with and without CAP. Methods Data and samples were collected and the expression of genes involved in metabolic stress and toxicity was analyzed in 26 individuals who had consented to participate in a natural history protocol. Subjects completed the 10-item Perceived Stress scale (PSS). Fasting participants’ peripheral whole blood was collected for proteomic and genomic studies. Polymerase chain reaction (PCR) array was used to analyze the expression of 84 key genes involved in human stress and toxicity plus 5 housekeeping genes. Plasma interleukin-1 alpha (IL-1α) protein was quantified via enzyme-linked immunosorbent assay (ELISA). Results Interleukin-1 alpha gene (IL1A) was upregulated in females with high stress versus females with low stress by 2.58-fold (95% CI [0.88, 4.28]). IL1A was upregulated in participants with high stress and CAP versus those with low stress and CAP by 3.47-fold (95% CI [1.14, 5.80]). Conclusions An upregulation of the gene coding the pro-inflammatory cytokine IL-1α suggests that the mechanism behind stress-related changes in GI symptoms is pro-inflammatory in nature. The results of this study contribute to the knowledge of the mechanism behind stress-related CAP symptoms and gender differences associated with these disorders.

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Preeclampsia annually kills 76,000 mothers and 500,000 babies worldwide often due to delay in diagnosis secondary to the lack ofsimple, early gestation tests. Elevated circulating copeptin (CPP), the pro-segment of vasopressin, is associated with preeclampsia (PreE). We have demonstrated that CPP is robustly predictive of PreE as early as the 6 th week of gestation in all mothers. Development of PreE is increased 3 fold by a history of PreE. Currently, no test robustly predicts PreE in women without a history of PreE. To evaluate if CPP is predictive in this low risk setting when a predictor is most needed, a nested case-control study was performed to evaluate the predictive characteristics of CPP of women with and without a history of PreE. Maternal plasma CPP concentrations throughout gestation were measured by ELISA. Univariate comparisons were performed. Receiver operating characteristic (ROC curves were constructed to determine sensitivity, specificity, positive and negative predictive values for particular cutoffs. Multivariable logistic regression was performed to control for confounding to examine if CPP was significantly predictive of PreE. Apart from a difference in prior history of PreE, no significant demographic or clinical differences were observed between groups. In all trimesters, CPP predicted PreE similarly or better in women with no history of PreE as evidenced by an elevated ROC Area Under the Curve in comparison to values of women with a history of Pre (1 st trimester: 0.96 vs. 0.85; 2 nd trimester: 0.95 vs. 0.94 ; 3 rd trimester: 0.82 vs. 0.67; p<0.05). Despite controlling for significant covariates such as maternal age, BMI, diabetes, chronic hypertension, and twin gestation, logistic modeling demonstrate that trimester specific CPP cutoffs throughout gestation are significantly associated with the development of PreE in women with no history of PreE (all models p< 0.001). Our data clearly support copeptin as an early predictor of preeclampsia in a low risk cohort. The ability to predict PreE in a low risk cohort with CPP is clinically significant as women in whom the diagnosis of preeclampsia is delayed or missed may now receive the appropriate interventions.

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