Reducing colonic mechanosensitivity is an important potential strategy for reducing visceral pain. Mice lacking acid‐sensing ion channels (ASIC) 1, 2, and 3 show altered colonic mechanosensory function, implicating ASICs in the mechanotransduction process. Deletion of ASICs affects mechanotransduction in visceral and cutaneous afferents differently, suggesting differential expression. We determined relative expression of ASIC1, 2, and 3 in mouse thoracolumbar dorsal root ganglia (DRG) by quantitative reverse‐transcriptase polymerase chain reaction (RT‐PCR) analysis (QPCR) and specifically in retrogradely traced colonic neurons isolated via laser capture microdissection. Localization of ASIC expression in DRG was determined with fluorescence in situ hybridization (FISH) and retrograde tracing. QPCR of whole thoracolumbar DRG revealed and abundance of ASIC2 > ASIC1 > ASIC3. Similarly, FISH of all neurons in thoracolumbar DRG demonstrated that ASIC2 was expressed in the most (40 ± 1%) neurons, followed by ASIC3 (24 ± 1%), then ASIC1 (18 ± 1%). Retrograde tracing from the distal colon labeled 4 ± 1% of neurons in T10‐L1 DRG. In contrast to whole DRG, FISH of colonic neurons showed ASIC3 expression in 73 ± 2%, ASIC2 in 47 ± 0.5%, and ASIC1 in 30 ± 2%. QPCR of laser captured colonic neurons revealed that ASIC3 was the most abundant ASIC transcript, followed by ASIC1, then ASIC2. We conclude that ASIC1, 2, and 3 are expressed preferentially in colonic neurons within thoracolumbar DRG. In particular ASIC3, the least abundant in the general population, is the most abundant ASIC transcript in colonic neurons. The prevalence of ASIC3 in neurons innervating the colon supports electrophysiological data showing that it makes a major contribution to colonic mechanotransduction and therefore may be a target for the treatment of visceral pain. J. Comp. Neurol. 500:863–875, 2007. © 2006 Wiley‐Liss, Inc.

Our study confirms previously reported findings that generalized obesity is an important risk factor for postmenopausal breast cancer, but only among women who have never taken HRT. Lifetime weight gain is also a strong predictor of breast cancer. Waist to hip ratio, a measure of weight distribution, does not appear to be related to postmenopausal breast cancer risk.

Purpose Few physical activity (PA) questionnaires were designed to measure the lifestyles and activities of women. We sought to examine the test-retest reliability of a PA questionnaire used in the Women's Health Initiative (WHI) Study. Differences in reliability were also explored by important covariates. Methods Participants (n=1092) were post-menopausal women aged 50-79 years, randomly selected from the baseline sample of participants in the WHI Observational Study. The WHI physical activity questionnaire collects usual frequency, duration, and pace of recreational walking, frequency and duration of other recreational activities or exercises (mild, moderate and strenuous), household, and yard activities. Approximately half of the women (n=569) repeated questions on recreational PA, the other half (n=523) repeated questions related to household and yard activities (mean 3 months apart). Test-retest reliability was assessed with kappa and intraclass correlation coefficients (ICC1,1). Results Overall, questions on recreational walking, moderate recreational PA, and strenuous recreational PA had higher test-retest reliability (weighted kappa range 0.50-0.60), than questions on mild recreational PA (weighted kappa range 0.35-0.50). The ICC1,1 for moderate to strenuous recreational PA was 0.77 (95% CI 0.73, 0.80) and total recreational PA was 0.76 (95% CI 0.71, 0.79). Substantial reliability was observed for the summary measures of yard activities (ICC1,1 0.71; 95% CI 0.66, 0.75) and household activities (ICC1,1 0.60, 95% CI 0.55, 0.66). No meaningful differences were observed by race/ethnicity, age, time between test and retest, and amount of reported PA. Conclusions The WHI PA questionnaire demonstrated moderate to substantial test-retest reliability in a diverse sample of post-menopausal women.

Current users of postmenopausal hormones (PMH) have f30% to 40% lower risk of colorectal cancer (CRC), although associations with specific types of hormones have been inconsistent. Further, it is not clear whether some tumor types have a different risk. We conducted a case-control study to examine the relationship between PMH and CRC. Cases (n = 1,004), ages 50 to 74 years, were identified from the Surveillance Epidemiology and End Results registry in Washington from 1998 to 2002; controls (n = 1,062) were randomly selected from population lists. Case tissue samples were obtained for microsatellite instability (MSI) analyses. Interviews collected risk-factor data for CRC, including detailed information on PMH. Multivariable logistic regression models estimated odds ratios (OR) and 95% confidence intervals (95% CI). Current use of any PMH was associated with a 20% reduction in CRC risk (95% CI 0.6-0.9). This reduction in risk was limited to women who had taken estrogen plus progestin (EP) preparations only (OR = 0.6, 95% CI 0.5-0.9); there was no association with estrogen-only (E alone) use (OR = 0.9, 95% CI 0.7-1.1). For women with MSI-low or MSI-stable tumors, there was a statistically significant 40% reduction in CRC risk associated with EP use (95% CI 0.4-0.9); there was no clear association with MSI-high tumors. EP use was associated with a decreased risk of CRC; however, there seemed to be no association with E alone data that are consistent with the recent Women's Health Initiative findings. Progestin may enhance the estrogenic effect of conjugated estrogen so the combination may be more biologically active in the colon than E alone. [Cancer Res 2007;67(15):7534-9]