Citations

Ano1 is a Ca 2+ activated Cl − channel expressed in several proliferating cell types including various epithelia, gastrointestinal stromal tumors, interstitial cells of Cajal (ICC) and CFPAC‐1 cells. The aim of this study was to determine if Ano1 regulates proliferation. ICC from Ano1 (−/−) and Ano1 (+/+) mice were cultured with Cl − channel inhibitors or in low Cl − media. CFPAC‐1 cells grown in low Cl − media were pulsed with EdU for 1 h. Incorporation was measured by flow cytometry. For immunoblots on mouse jejunum, antibodies to pRb, phospho(Ser773)‐pRb and GAPDH were used. Fewer proliferating ICC were detected in Ano1 (−/−) cultures (15 ± 3.5% Ki67 + ICC vs 25 ± 4% in Ano1 (+/+) , mean ± SEM, n = 4, p < 0.05). Cl − channel inhibitors DIDS (10 μM), niflumate (10 μM) and tamoxifen (1 μM) decreased ICC proliferation by 53, 53 and 59%, respectively ( p < 0.05). This effect was reduced in cultures from Ano1 (−/−) mice (29% and 19 % decrease, 22% increase, p > 0.05). Fewer proliferating ICC and CFPAC‐1 cells were detected in low Cl − media (% EdU + ICC: 120 mM; 19.8 ± 5.3, 12 mM; 8.5 ± 3.2, n = 4, and % EdU + CFPAC‐1: 120 mM; 29.5, 12 mM; 14.3 p < 0.05). Proportionally less Ser773‐phosphorylated pRb was detected in jejunum from Ano1 (−/−) mice (Ano1 (+/+) ; 5.98 ± 0.78, Ano1 (−/−) ; 3.60 ± 0.49, mean ± SEM, n = 7, p < 0.05). In conclusion, Ano1 regulates proliferation possibly by promoting the G 1 /S transition of the cell cycle. Support: DK57061 and DK68055.

The antihypertensive influence of fish oil is controversial, and mechanisms remain unclear. We tested the hypothesis that fish oil reduces mean arterial pressure (MAP) via reductions in muscle sympathetic nerve activity (MSNA). Because the inverse relation between fish oil and hypertension appears to be dependent on the degree of hypertension, we also tested the hypothesis that fish oil would elicit more dramatic reductions in MAP and MSNA in prehypertensive (PHT) compared to normotensive (NT) subjects. Resting MAP, MSNA, and heart rate (HR) were examined before and after 8 wk of fish oil (9g/day) or placebo (olive oil; 9g/day) in 38 NT (19 fish oil; 19 placebo) and 29 PHT (15 fish oil; 14 placebo) volunteers. Fish oil did not alter resting MAP, MSNA, or HR in either NT (71±2 to 71±2 mmHg; 11±2 to 10±1 bursts/min; 80±1 to 80±1 beats/min) or PHT (88±2 to 87±1 mmHg; 11±2 to 10±2 bursts/min; 73±2 to 73±2 beats/min) subjects. However, when NT and PHT groups were consolidated, a significant correlation was observed between changes in MAP and changes in MSNA in the fish oil group (r=0.354, p=0.035). In conclusion, fish oil did not alter neural cardiovascular control in NT or PHT. However, interindividual MAP responses to fish oil appear to be moderately associated with changes in MSNA, suggesting that the sympathetic nervous system may contribute to the inconsistent antihypertensive response of fish oil. Supported by NIH (HL‐088689).

Some studies report an increase of resting muscle sympathetic nerve activity (MSNA) during the midluteal (ML) phase of the menstrual cycle when compared to the early follicular phase (EF), while others do not. The inconsistent findings may be due, in part, to variable surges in estradiol and progesterone. We tested the hypothesis that the degree of sympathoexcitation during the ML phase (ΔMSNA) is associated with changes in estradiol (ΔE 2 ) and progesterone (ΔP). Retrospective analysis of previous studies with recordings of mean arterial pressure (MAP), MSNA, E 2 , and P during both EF and ML phases yielded 30 eumenorrheic women (age, 18–51 yrs). ML phase increased E 2 (37±2 to 117±9 pg/ml; p<.001), P (1±0 to 11±1 ng/ml; p<.001), and MSNA (12±1 to 15±1 bursts/min; p=.02), but did not alter MAP (83±2 to 83±2 mmHg; p=.91). ΔMSNA was correlated to ΔE 2 (r=−.50, p=.005) and ΔE 2 /ΔP (r=−.52, p=.004), but not ΔP (r=.21, p=.26). There was no association between ΔMAP and ΔE 2 (r=−.13, p=.49), ΔP (r=−.04, p=.83), or ΔE 2 /ΔP (r<.01, p=.98). In conclusion, sympathoexcitatory responses to the ML phase appear to be associated with the degree of sex steroid surges. While E 2 had a stronger influence on MSNA than P, it is worthy to note that a strong association with ΔMSNA persisted when both ΔE 2 and ΔP were considered. This dynamic interaction between E 2 , P, and MSNA likely explains previously reported inconsistencies in the field. Supported by NIH.

Omega‐3 fatty acids found in fish oil have been suggested to protect against cardiovascular disease, yet underlying mechanisms remain unclear. Given the well documented links between mental stress (MS) and cardiovascular risk, we hypothesized that fish oil would blunt blood pressure (BP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) responsiveness to MS. Neural and cardiovascular responses to a 5 min mental arithmetic protocol were recorded in 67 non‐hypertensive subjects before and after 8 wks of fish oil (9g/day; n=33) or placebo (olive oil; 9g/day; n=34). Fish oil blunted HR reactivity to MS (group × condition × time interaction, P=0.012), but did not alter BP reactivity (interactions, P>;0.05). Fish oil blunted total MSNA reactivity to MS (interaction, P=0.039), but did not alter MSNA burst frequency and burst incidence reactivity (interactions, P>;0.05). Finally, fish oil significantly blunted calf vascular conductance (CVC) reactivity to MS (interaction, P=0.013), but did not alter forearm vascular conductance reactivity (interaction, P>;0.05). In conclusion, 8 wks of fish oil supplementation significantly attenuated HR and total MSNA reactivity to MS, and elicited a paradoxical blunting of CVC. These findings support and extend the growing evidence that fish oil may have positive health benefits regarding neural cardiovascular control in humans. Supported by NIH (HL‐088689).

INTRODUCTION: Significant variability between colonoscopy operators contributes to postcolonoscopy colorectal cancers (CRCs). We aimed to estimate postcolonoscopy colorectal neoplasia (CRN) detection by multi-target stool DNA (mt-sDNA), which has not previously been studied for this purpose. METHODS: In a retrospective cohort of patients with +mt-sDNA and completed follow-up colonoscopy, positive predictive value (PPV) for endpoints of any CRN, advanced adenoma, right-sided neoplasia, sessile serrated polyps (SSP), and CRC were stratified by the time since previous colonoscopy (0–9, 10, and ≥11 years). mt-sDNA PPV at ≤9 years from previous average-risk screening colonoscopy was used to estimate CRN missed at previous screening colonoscopy. RESULTS: Among the 850 studied patients with +mt-sDNA after a previous negative screening colonoscopy, any CRN was found in 535 (PPV 63%). Among 107 average-risk patients having +mt-sDNA ≤9 years after last negative colonoscopy, any CRN was found in 67 (PPV 63%), advanced neoplasia in 16 (PPV 15%), right-sided CRN in 48 (PPV 46%), and SSP in 20 (PPV 19%). These rates were similar to those in 47 additional average risk persons with previous incomplete colonoscopy and in an additional 68 persons at increased CRC risk. One CRC (stage I) was found in an average risk patient who was mt-sDNA positive 6 years after negative screening colonoscopy. DISCUSSION: The high PPV of mt-sDNA 0–9 years after a negative screening colonoscopy suggests that lesions were likely missed on previous examination or may have arisen de novo . mt-sDNA as an interval test after negative screening colonoscopy warrants further study.

Effective communication of medical information by doctors to patients has been found to be positively related to patient satisfaction. In the United States ACGME requires doctors in training to meet the competency of effective communication across many socioeconomic and cultural backgrounds. One of the main contributors to ineffective patient communication is inaccurate perception by the doctor about the extent of a patient's medical knowledge. This study seeks to elucidate medical student perceptions of patients’ knowledge of anatomy based on patient age, sex, occupation, education level and race. It also seeks to understand which of these matter most in guiding students’ assumptions. Patients were asked to complete a questionnaire, created in collaboration with the Mayo Clinic Patient Education Center, which included a multiple choice anatomy quiz and demographic information. First year medical students who had just completed their gross anatomy course were given the same anatomy quiz and a survey that included the demographic profiles of the patients. They were then asked to predict how well the patients scored. Student perceptions of patient knowledge were compared to the actual scores. Pending the results of this study, we anticipate that medical students will over‐estimate patients’ anatomical knowledge. This project was funded by the Department of Anatomy, Mayo Clinic, Rochester, MN.

The relationship between mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and total peripheral resistance (TPR) is altered in young women versus men and postmenopausal women due to endogenous sex hormone differences. Exogenous sex hormones in the form of oral contraceptive pills (OCPs) may further affect this relationship. We performed a retrospective review of 136 premenopausal women in whom MSNA and arterial pressure were measured, including 78 women with natural menstrual cycles in the early follicular phase (26±1 yr) and 58 women in the placebo phase of OCPs (24±1 yr). TPR and cardiac output (CO) were measured in a subset of women in whom continuous intra‐arterial blood pressure was recorded. Compared to those with natural menstrual cycles, women on OCPs had greater MAP (89±1 vs. 84±1 mmHg, p<0.01) and tended to have lower MSNA (15±1 vs. 18±1 bursts/100 heart beats, p=0.06). MAP and MSNA were positively correlated (r=0.22, p<0.05), TPR and MSNA were positively associated (r=0.41, p<0.05) and CO and MSNA (r=‐0.44, p<0.05) were inversely associated in naturally cycling women (n=26) but not in women on OCPs (r=0.15, r=0.11, r=‐0.01, respectively; p>0.05; n=38). In contrast to naturally cycling women, there appears to be no relationship between MSNA and hemodynamics in women on OCPs, suggesting that these women may regulate their blood pressure differently than women. Grant Funding Source : Supported by NIH