c-Rel orchestrates energy-dependent epithelial and macrophage reprogramming in fibrosis.

Fibrosis is a common pathological feature of chronic disease. Deletion of the NF-κB subunit c-Rel limits fibrosis in multiple organs, although the mechanistic nature of this protection is unresolved. Using cell-specific gene-targeting manipulations in mice undergoing liver damage, we elucidate a critical role for c-Rel in controlling metabolic changes required for inflammatory and fibrogenic activities of hepatocytes and macrophages and identify Pfkfb3 as the key downstream metabolic mediator of this response. Independent deletions of Rel in hepatocytes or macrophages suppressed liver fibrosis induced by carbon tetrachloride, while combined deletion had an additive anti-fibrogenic effect. In transforming growth factor-ß1-induced hepatocytes, c-Rel regulates expression of a pro-fibrogenic secretome comprising inflammatory molecules and connective tissue growth factor, the latter promoting collagen secretion from HMs. Macrophages lacking c-Rel fail to polarize to M1 or M2 states, explaining reduced fibrosis in RelΔLysM mice. Pharmacological inhibition of c-Rel attenuated multi-organ fibrosis in both murine and human fibrosis. In conclusion, activation of c-Rel/Pfkfb3 in damaged tissue instigates a paracrine signalling network among epithelial, myeloid and mesenchymal cells to stimulate fibrogenesis. Targeting the c-Rel-Pfkfb3 axis has potential for therapeutic applications in fibrotic disease.

Fecal incontinence in obese women with urinary incontinence: prevalence and role of dietary fiber intake.

OBJECTIVE: This study estimates the prevalence of fecal incontinence (FI) in overweight and obese women with urinary incontinence and compares dietary intake in women with and without FI. STUDY DESIGN: A total of 336 incontinent and overweight women in the Program to Reduce Incontinence by Diet and Exercise clinical trial were included. FI was defined as monthly or greater loss of mucus, liquid, or solid stool. Dietary intake was quantified using the Block Food Frequency Questionnaire. RESULTS: Women had a mean (+/- SD) age of 53 +/- 10 years, body mass index of 36 +/- 6 kg/m(2), and 19% were African American. Prevalence of FI was 16% (n = 55). In multivariable analyses, FI was independently associated with low fiber intake, higher depressive symptoms, and increased urinary tract symptoms (all P < .05). CONCLUSION: Overweight and obese women report a high prevalence of monthly FI associated with low dietary fiber intake. Increasing dietary fiber may be a treatment for FI.

Additional self-monitoring tools in the dietary modification component of The Women's Health Initiative.

Self-monitoring promotes behavior changes by promoting awareness of eating habits and creates self-efficacy. It is an important component of the Women's Health Initiative dietary intervention. During the first year of intervention, 74% of the total sample of 19,542 dietary intervention participants self-monitored. As the study progressed the self-monitoring rate declined to 59% by spring 2000. Participants were challenged by inability to accurately estimate fat content of restaurant foods and the inconvenience of carrying bulky self-monitoring tools. In 1996, a Self-Monitoring Working Group was organized to develop additional self-monitoring options that were responsive to participant needs. This article describes the original and additional self-monitoring tools and trends in tool use over time. Original tools were the Food Diary and Fat Scan. Additional tools include the Keeping Track of Goals, Quick Scan, Picture Tracker, and Eating Pattern Changes instruments. The additional tools were used by the majority of participants (5,353 of 10,260 or 52% of participants who were self-monitoring) by spring 2000. Developing self-monitoring tools that are responsive to participant needs increases the likelihood that self-monitoring can enhance dietary reporting adherence, especially in long-term clinical trials.