Circadian changes in PACAP type 1 (PAC1) receptor mRNA in the rat suprachiasmatic and supraoptic nuclei

A receptor for pituitary adenylate cyclase activating polypeptide (PACAP), denoted as PAC₁, is expressed in the suprachiasmatic nuclei (SCN). Since the circadian clock demonstrates phase-dependent sensitivity to PACAP, we have used in situ hybridization histochemistry to examine whether PAC₁ mRNA is differentially expressed in the rat SCN across the 24-h cycle. There was a significant variation in PAC₁ mRNA within the SCN and supraoptic nuclei during the light–dark cycle and in constant darkness, with peaks at the middle of both the real and subjective day and night; no significant variation was observed in the cingulate cortex. The results suggest that the phase-dependent actions of PACAP on the clock may involve phase-specific changes in the availability of PAC₁ receptors within the SCN.     

Target definition in prostate, head, and neck

Target definition is a major source of errors in both prostate and head and neck external-beam radiation treatment. Delineation errors remain constant during the course of radiation and therefore have a large impact on the dose to the tumor. Major sources of delineation variation are visibility of the target including its extensions, disagreement on the target extension, and interpretation or lack of delineation protocols. The visibility of the target can be greatly improved with the use of multimodality imaging. Both in the head and neck and the prostate, computed tomography (CT)-magnetic resonance imaging coregistration decreases the target volume and its variability. CT-positron emission tomography delineation is promising for delineation in head and neck cancer. Despite the better visibility, a different interpretation of the target extension remains a major source of error. The use of coregistration of CT with a second modality, together with improved guidelines for delineation and an online anatomical atlas, increases agreement between observers in prostate, lung, and nasopharynx tumors. Delineation errors should not be treated differently from other geometrical errors. Similar margin recipes for the correction of setup errors and organ motion should be adapted to incorporate the effect of delineation errors. A calculation of a 3-dimensional clinical target volume-planning target volume margin incorporating delineation errors for the head and neck is around 6.1 to 9.7 mm. Given the good local control of IMRT with smaller margins and smaller pathological specimens, it is likely that the delineated CTV frequently overestimates the actual volume.     

Homocysteine and the kidney

Plasma homocysteine concentration exhibits a strong relationship with (indices of) renal function. Hyperhomocysteinemia has been implicated in the high vascular event rate in patients with chronic renal failure. The precise pathophysiological explanation for the occurrence of hyperhomocysteinemia in renal failure is not yet elucidated. A defective intrinsic renal metabolism of homocysteine seems unlikely. There are several indications that whole body homocysteine metabolism is altered in renal insufficiency. Stable isotope studies in dialysis patients have shown a decreased homocysteine clearance by transsulfuration and decreased homocysteine remethylation and methionine transmethylation. Several, but not all, prospective studies have linked hyperhomocysteinemia to adverse cardiovascular outcomes in renal failure patients. Treatment of hyperhomocysteinemia in renal insufficiency is based on folic acid-containing regimens, but so far, none of the regimens has been shown to successfully normalize plasma homocysteine concentration. Intervention studies have not yet demonstrated beneficial vascular effects of homocysteine-lowering treatment in dialysis patients.     

Smoking prevalence and correlates among Chinese- and Filipino-American adults: findings from the 2001 California Health Interview Survey

OBJECTIVES: We report prevalence rates and correlates of cigarette smoking among a population-based sample of Chinese- and Filipino-American adults together with rates found in other racial/ethnic groups in California. METHODS: All analyses are based on the 2001 California Health Interview Survey. RESULTS: The proportion of current smokers among males was lowest among Chinese Americans (14%), followed by Non-Hispanic Whites (19%), Hispanics (20%), African Americans (22%), Filipino Americans (24%), American Indians/Alaska Natives (29%), and Pacific Islanders (32%). The proportion of current smokers among females was lowest among Chinese Americans (6%), followed by Hispanics (8%), Filipino Americans (11%), Non-Hispanic Whites (17%), African Americans (20%), Pacific Islander (21%), and American Indians/Alaska Natives (32%). Smoking rates were higher among foreign-born versus U.S.-born Asian males. CHIS data show an opposite effect among Asian women: acculturation to the U.S. is associated with increased smoking prevalence rates. Multivariate analyses with Chinese and Filipino respondents showed that the likelihood of smoking varied among foreign-born versus U.S.-born men (OR 2.59 for Chinese, 1.42 for Filipino, 2.01 for all Asian men combined) and for foreign-born versus U.S.-born women (OR 0.41 for Chinese, 0.38 for Filipino, and 0.59 for all Asian women combined). CONCLUSION: Public health intervention efforts should take into account Asian ethnic subgroup, gender, and acculturation status in targeting high-risk smoking groups.     

Increased plasma aldosterone in patients with clinical depression

BACKGROUND: Clinical depression has been increasingly recognized as an independent risk factor for adverse cardiovascular events, but the biological mechanisms of this association remain unclear. Recent evidence for renin system dysregulation in patients with depression led us to hypothesize that aldosterone--a well-recognized contributor to vascular injury--could be increased in depressed patients. The present study was designed, therefore, to be a cross-sectional investigation of plasma renin and aldosterone levels in depressed patients as compared with healthy controls with no history of psychiatric illness. METHODS: A total of 65 depressed patients and 65 age- and gender-matched control subjects were enrolled. Following a fixed sodium and potassium diet, venous blood samples were obtained at 9:00 a.m. to avoid the influence of circadian rhythms. RESULTS: Although there were no significant differences in plasma level of renin among subjects with depression and controls (7.9 +/- 5.8 vs. 6.4 +/- 4.3 pg/mL, respectively; p=0.10), depressed subjects exhibited greater mean aldosterone levels as compared with control subjects (157.2 +/- 67.5 vs. 125.7 +/- 38.1 pg/mL, respectively; p=0.0014). After adjusting for potential confounders, multivariate logistic regression analysis showed that subjects with depression had 2.77 times higher odds of elevated aldosterone levels compared with healthy control subjects (95% confidence interval, 1.30-5.92, p=0.008). CONCLUSIONS: Our present findings support the hypothesis that hyperaldosteronism could be a common feature among depressed patients, thereby suggesting that increased aldosterone levels may act as a mediator in the pathway linking depression to unfavorable vascular events.     

Competition between methicillin-sensitive and -resistant Staphylococcus aureus in the anterior nares

Colonization of the anterior nares with Staphylococcus aureus has been shown to be a risk factor for infection. The purpose of this study was to test the hypothesis that methicillin-resistant strains of S. aureus (MRSA) compete with methicillin-sensitive (MSSA) strains for colonization of the anterior nares. As part of the local National Health Service trust MRSA infection control strategy, patients who have been in a healthcare institution in the last year are routinely sampled and tested for MRSA colonization at the time of hospital admission. The sampling and testing methods were modified for the six-month period of this study to allow the detection of both MSSA and MRSA/MSSA co-colonization. MRSA alone was carried by 56 (8%) of 680 patients, MSSA alone by 115 patients (17%), 505 patients (74.3%) carried neither, and four patients (0.6%) carried both MRSA and MSSA. The deviance between the observed number of co-colonized swabs and that expected under the null hypothesis of no competition between MSSA and MRSA was significant (P=0.02, Fisher's exact test). The statistical approach is unaffected by the confounding effect of factors that affect the relative frequencies of MRSA or MSSA colonization. When logistic regression was used to estimate the extent of competition, controlling for effects of age and sex, we estimated a protective efficacy of MSSA colonization in the prevention of MRSA colonization of 78% (95% CI 29-99%). Results from this cross-sectional study support the hypothesis that MRSA and MSSA compete for colonization space, and provides an estimate of the extent to which MSSA interferes with MRSA colonization.     

Proinsulin concentration is an independent predictor of all-cause and cardiovascular mortality: an 11-year follow-up of the Hoorn Study

OBJECTIVE: High proinsulin concentration may be a better predictor for cardiovascular disease (CVD) mortality than insulin concentration. Previous observations may have been confounded by glucose tolerance status or lack of precision because of high intraindividual variability. We investigated the longitudinal relation of means of duplicate measurements of insulin and proinsulin with all-cause and CVD mortality in a population-based cohort taking glucose tolerance status into account. RESEARCH DESIGN AND METHODS: Fasting and post-75-g glucose-load (2-h) glucose, insulin, and proinsulin values were determined in duplicate on separate days in 277 participants with normal glucose metabolism, 208 participants with impaired glucose metabolism, and 119 newly detected patients with type 2 diabetes of the Hoorn Study. Insulin resistance and beta-cell function were estimated by homeostasis model assessment (HOMA-IR and HOMA-B, respectively), and the fasting proinsulin-to-insulin ratio was calculated. Subjects were followed with respect to mortality until January 2003. RESULTS: Fasting proinsulin levels were significantly associated with all-cause and CVD mortality. The hazard ratios (HRs) per increase in interquartile range adjusted for age and sex were 1.21 (95% CI 1.04-1.42) for all-cause mortality and 1.33 (1.06-1.66) for CVD mortality. Adjustment for glucose tolerance status and HOMA-IR did not substantially change the associations. CONCLUSIONS: Fasting proinsulin was associated with all-cause and CVD mortality, independent of glucose tolerance status and insulin resistance and largely independent of other CVD risk factors. Proinsulin might play a role in the relationship between insulin resistance and CVD.     

Effects of exercise adherence on physical function among overweight older adults with knee osteoarthritis

OBJECTIVE: To determine whether high exercise adherence improved physical function among older adults with knee osteoarthritis (OA) who were overweight or obese. METHODS: Associations between exercise adherence, changes in 6-minute walking distance in meters, and self-reported disability (Western Ontario and McMaster Universities Osteoarthritis Index function subscale) after 6 and 18 months were examined among an Arthritis, Diet, and Activity Promotion Trial subsample (n = 134) using multiple linear regression models. RESULTS: Higher exercise adherence was associated with greater improvements in 6-minute walking distance after 6 and 18 months and in disability after 6 months. Pain and body mass index (BMI) contributed, to some extent, to explaining the link between exercise adherence and changes in physical performance and self-reported disability. CONCLUSION: Higher exercise adherence is associated with improved physical function in overweight and obese older adults with knee OA. This indicates that promoting adherence is clinically relevant when prescribing exercise regimens that also focus on decreasing pain and BMI.