Folic Acid and Risk of Prostate Cancer: Results From a Randomized Clinical Trial

Data regarding the association between folate status and risk of prostate cancer are sparse and conflicting. We studied prostate cancer occurrence in the Aspirin/Folate Polyp Prevention Study, a placebo-controlled randomized trial of aspirin and folic acid supplementation for the chemoprevention of colorectal adenomas conducted between July 6, 1994, and December 31, 2006. Participants were followed for up to 10.8 (median = 7.0, interquartile range = 6.0–7.8) years and asked periodically to report all illnesses and hospitalizations. Aspirin alone had no statistically significant effect on prostate cancer incidence, but there were marked differences according to folic acid treatment. Among the 643 men who were randomly assigned to placebo or supplementation with folic acid, the estimated probability of being diagnosed with prostate cancer over a 10-year period was 9.7% (95% confidence interval [CI] = 6.5% to 14.5%) in the folic acid group and 3.3% (95% CI = 1.7% to 6.4%) in the placebo group (age-adjusted hazard ratio = 2.63, 95% CI = 1.23 to 5.65, Wald test P = .01). In contrast, baseline dietary folate intake and plasma folate in nonmultivitamin users were inversely associated with risk of prostate cancer, although these associations did not attain statistical significance in adjusted analyses. These findings highlight the potential complex role of folate in prostate cancer and the possibly different effects of folic acid–containing supplements vs natural sources of folate

The ‘microflora hypothesis’ of allergic diseases

Increasingly, epidemiologic and clinical data support the hypothesis that perturbations in the gastrointestinal (GI) microbiota because of antibiotic use and dietary differences in ‘industrialized’ countries have disrupted the normal microbiota-mediated mechanisms of immunological tolerance in the mucosa, leading to an increase in the incidence of allergic airway disease. The data supporting this ‘microflora hypothesis’ includes correlations between allergic airway disease and (1) antibiotic use early in life, (2) altered fecal microbiota and (3) dietary changes over the past two decades. Our laboratory has recently demonstrated that mice can develop allergic airway responses to allergens if their endogenous microbiota is altered at the time of first allergen exposure. These experimental and clinical observations are consistent with other studies demonstrating that the endogenous microbiota plays a significant role in shaping the development of the immune system. Data are beginning to accumulate that a ‘balanced’ microbiota plays a positive role in maintaining mucosal immunologic tolerance long after post-natal development. Other studies have demonstrated that even small volumes delivered to the nasopharynx largely end up in the GI tract, suggesting that airway tolerance and oral tolerance may operate simultaneously. The mechanism of microbiota modulation of host immunity is not known; however, host and microbial oxylipins are one potential set of immunomodulatory molecules that may control mucosal tolerance. The cumulative data are beginning to support the notion that probiotic and prebiotic strategies be considered for patients coming off of antibiotic therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73451/1/j.1365-2222.2005.02379.x.pd

Serum endotoxins and flagellin and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

Background: Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer development. These processes may contribute to leakage of bacterial products, such as lipopolysaccharide (LPS) and flagellin, across the gut barrier. The objective of this study, nested within a prospective cohort, was to examine associations between circulating LPS and flagellin serum antibody levels and colorectal cancer risk. Methods: A total of 1,065 incident colorectal cancer cases (colon, n = 667; rectal, n = 398) were matched (1:1) to control subjects. Serum flagellin- and LPS-specific IgA and IgG levels were quantitated by ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI), adjusting for multiple relevant confouding factors. Results: Overall, elevated anti-LPS and anti-flagellin biomarker levels were not associated with colorectal cancer risk. After testing potential interactions by various factors relevant for colorectal cancer risk and anti-LPS and anti-flagellin, sex was identified as a statistically significant interaction factor (Pinteraction < 0.05 for all the biomarkers). Analyses stratified by sex showed a statistically significant positive colorectal cancer risk association for men (fully-adjusted OR for highest vs. lowest quartile for total anti-LPS + flagellin, 1.66; 95% CI, 1.10–2.51; Ptrend, 0.049), whereas a borderline statistically significant inverse association was observed for women (fully-adjusted OR, 0.70; 95% CI, 0.47–1.02; Ptrend, 0.18). Conclusion: In this prospective study on European populations, we found bacterial exposure levels to be positively associated to colorectal cancer risk among men, whereas in women, a possible inverse association may exist. Impact: Further studies are warranted to better clarify these preliminary observations

Lifetime body size and reproductive factors: comparisons of data recorded prospectively with self reports in middle age

<p>Abstract</p> <p>Background</p> <p>Data on lifetime exposures are often self-reported in epidemiologic studies, sometimes many years after the relevant age. Validity of self-reported data is usually inferred from their agreement with measured values, but few studies directly quantify the likely effects of reporting errors in body size and reproductive history variables on estimates of disease-exposure associations.</p> <p>Methods</p> <p>The MRC National Survey of Health and Development (NSHD) and the Million Women Study (MWS) are UK population-based prospective cohorts. The NSHD recruited participants at birth in 1946 and has followed them at regular intervals since then, whereas the MWS recruited women in middle age. For 541 women who were participants in both studies, we used statistical measures of association and agreement to compare self-reported MWS data on body size throughout life and reproductive history, obtained in middle age, to NSHD data measured or reported close to the relevant ages. Likely attenuation of estimates of linear disease-exposure associations due to the combined effects of random and systematic errors was quantified using regression dilution ratios (RDRs).</p> <p>Results</p> <p>Data from the two studies were very strongly correlated for current height, weight and body mass index, and age at menopause (Pearson r = 0.91-0.95), strongly correlated for birth weight, parental heights, current waist and hip circumferences and waist-to-height ratio (r = 0.67-0.80), and moderately correlated for age at menarche and waist-to-hip ratio (r = 0.52-0.57). Self-reported categorical body size and clothes size data for various ages were moderately to strongly associated with anthropometry collected at the relevant times (Spearman correlations 0.51-0.79). Overall agreement between the studies was also good for most quantitative variables, although all exhibited both random and systematic reporting error. RDRs ranged from 0.66 to 0.86 for most variables (slight to moderate attenuation), except weight and body mass index (1.02 and 1.04, respectively; little or no attenuation), and age at menarche, birth weight and waist-to-hip ratio (0.44, 0.59 and 0.50, respectively; substantial attenuation).</p> <p>Conclusions</p> <p>This study provides some evidence that self-reported data on certain anthropometric and reproductive factors may be adequate for describing disease-exposure associations in large epidemiological studies, provided that the effects of reporting errors are quantified and the results are interpreted with caution.</p

Induction of Heme Oxygenase-1 Can Halt and Even Reverse Renal Tubule-Interstitial Fibrosis

Background: The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed. Aim: We explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease. Methods: Sprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO) and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed. Results: Pre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-beta protein production was significantly lower in Hemin-treated animals. Conclusion: Treatment with Hemin was able both to prevent the progression of fibrosis and to reverse an established renal scar. Modulation of inflammation appears to be the major mechanism behind HO-1 cytoprotection.Fundacao de Amparo Pesquisa do Estado de Sao Paulo-FAPESP[07/07139-3]Coordenaco de Aperfeioamento de Pessoal de Nivel Superior-CAPESInstituto Nacional de Ciencia e Tecnologia de Complexos Fluidos (INCT)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNP

A pilot randomised controlled trial to reduce colorectal cancer risk markers associated with B-vitamin deficiency, insulin resistance and colonic inflammation

Colorectal cancer risk is associated with biochemical markers for B-vitamin deficiency, insulin resistance and colonic inflammation, suggesting that these three conditions are each involved in colon carcinogenesis. We expected that dietary supplements of folic acid, n-3 fatty acids and calcium would reduce the markers and thus possibly cancer risk. We therefore randomised 98 participants, with previous colonic polyps or intramucosal carcinomas, to a combined treatment of supplementary folic acid, fish oil and calcium carbonate, or placebos for 28 days. Blood and faecal samples were obtained prior to and at the conclusion of the intervention and analysed for plasma folate, homocysteine, insulin, free fatty acids, triglycerides and faecal calprotectin. In addition, plasma vitamin B12, thiamin, glucose and C-reactive protein were assessed. Our supplemental strategy modestly affected some of the biomarkers associated with folate metabolism and insulin resistance, but had no effect on those associated with colonic inflammation. This pilot study demonstrates the feasibility and practicality of clinical trials aimed at reducing diet-related biochemical risk markers for colon cancer. We suggest that long-term intervention studies with tumour-related end points should be undertaken when the intervention agents used are found effective in short-term biochemical risk marker trials

Valid and reliable instruments for arm-hand assessment at ICF activity level in persons with hemiplegia: a systematic review

Contains fulltext : 110141.pdf (publisher's version ) (Open Access)BACKGROUND: Loss of arm-hand performance due to a hemiparesis as a result of stroke or cerebral palsy (CP), leads to large problems in daily life of these patients. Assessment of arm-hand performance is important in both clinical practice and research. To gain more insight in e.g. effectiveness of common therapies for different patient populations with similar clinical characteristics, consensus regarding the choice and use of outcome measures is paramount. To guide this choice, an overview of available instruments is necessary. The aim of this systematic review is to identify, evaluate and categorize instruments, reported to be valid and reliable, assessing arm-hand performance at the ICF activity level in patients with stroke or cerebral palsy. METHODS: A systematic literature search was performed to identify articles containing instruments assessing arm-hand skilled performance in patients with stroke or cerebral palsy. Instruments were identified and divided into the categories capacity, perceived performance and actual performance. A second search was performed to obtain information on their content and psychometrics. RESULTS: Regarding capacity, perceived performance and actual performance, 18, 9 and 3 instruments were included respectively. Only 3 of all included instruments were used and tested in both patient populations. The content of the instruments differed widely regarding the ICF levels measured, assessment of the amount of use versus the quality of use, the inclusion of unimanual and/or bimanual tasks and the inclusion of basic and/or extended tasks. CONCLUSIONS: Although many instruments assess capacity and perceived performance, a dearth exists of instruments assessing actual performance. In addition, instruments appropriate for more than one patient population are sparse. For actual performance, new instruments have to be developed, with specific focus on the usability in different patient populations and the assessment of quality of use as well as amount of use. Also, consensus about the choice and use of instruments within and across populations is needed