Meat and Components of Meat and the Risk of Bladder Cancer in the NIH-AARP Diet and Health Study

BACKGROUND: Meat could be involved in bladder carcinogenesis via multiple potentially carcinogenic meat-related compounds related to cooking and processing, including nitrate, nitrite, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs). The authors comprehensively investigated the association between meat and meat components and bladder cancer. METHODS: During 7 years of follow-up, 854 transitional cell bladder-cancer cases were identified among 300,933 men and women who had completed a validated food-frequency questionnaire in the large prospective NIH-AARP Diet and Health Study. The authors estimated intake of nitrate and nitrite from processed meat and HCAs and PAHs from cooked meat by using quantitative databases of measured values. Total dietary nitrate and nitrite were calculated based on literature values. RESULTS: The hazard ratios (HR) and 95% confidence intervals (CI) for red meat (HR for fifth quintile compared with first quintile, 1.22; 95% CI, 0.96-1.54; Ptrend = .07) and the HCA 2-amino-1 methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) (HR, 1.19; 95% CI, 0.95-1.48; Ptrend = .06) conferred a borderline statistically significant increased risk of bladder cancer. Positive associations were observed in the top quintile for total dietary nitrite (HR, 1.28; 95% CI, 1.02-1.61; Ptrend = .06) and nitrate plus nitrite intake from processed meat (HR, 1.29; 95% CI, 1.00-1.67; Ptrend = .11). CONCLUSIONS: These findings provided modest support for an increased risk of bladder cancer with total dietary nitrite and nitrate plus nitrite from processed meat. Results also suggested a positive association between red meat and PhIP and bladder carcinogenesis

Situating Speech: A Rhetorical Approach to Political Strategy

Ideas are increasingly acknowledged as factors in explaining political behaviour. But often they are treated as inert resources rather than dynamic instances of action in themselves. The latter, I propose, requires reflection on the character of speech – as the medium of ideas – in responding to and refiguring a prevailing situation. I undertake such reflection by setting out a rhetorical approach to political strategy. Building upon ‘interpretive’ advances in political science I shift the focus from stable cognitive frames to the dynamics of argumentation where ideas work expressively. I then explore the rhetorical aspect of strategising with attention to the way speech serves to orient audiences by creatively re-appropriating a situation. That approach is shown to be consistent with a ‘dialectical’ political sociology that emphasises the interaction of structure and agency. Finally, I sketch a method for undertaking rhetorical analysis and indicate how it might be applied to a concrete example

Diabetes prevalence is associated with serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in US middle-aged Caucasian men and women: a cross-sectional analysis within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Hypovitaminosis D may be associated with diabetes, hypertension and CHD. However, because studies examining the associations of all three chronic conditions with circulating 25-hydroxyvitamin D (25(0H)D) and 1,25-dihydroxyvitamin D (1,25(0H)2D) are limited, we examined these associations in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (n 2465). Caucasian PLCO participants selected as controls in previous nested case-control studies of 25(0H)D and 1,25(0H)2D were included in this analysis. Diabetes, CHD and hypertension prevalence, risk factors for these conditions and intake of vitamin D and Ca were collected from a baseline questionnaire. Results indicated that serum levels of 25(0H)D were low (\u3c50nmol/1) in 29% and very low ( \u3c 37nmol/1) in 11% of subjects. The prevalence of diabetes, hypertension and CHD was 7, 30 and 10%, respectively. After adjustment for confounding by sex, geographical location, educational level, smoking history, BMI, physical activity, total dietary energy and vitamin D and Ca intake, only diabetes was significantly associated with lower 25(0H)D and 1,25(0H)2D levels. Caucasians who had 25(0H)D 2:80nmol/1 were half as likely to have diabetes (OR 0·5 (95% Cl 0·3, 0·9)) compared with those who had 25(0H)D /l. Those in the highest quartile of 1,25(0H)2D (/1) were less than half as likely to have diabetes (OR 0·3 (95% Cl 0·1, 0·7)) than those in the lowest quartile (\u3c 72pmol/l). In conclusion, the independent associations of 25(0H)D and 1,25(0H)2D with diabetes prevalence in a large population are new findings, and thus warrant confirmation in larger, prospective studies

Delayed-type hypersensitivity in classic Kaposi sarcoma patients and controls

BACKGROUND: Immune perturbation likely affects the development of Kaposi sarcoma (KS) among people infected with the KS-associated herpesvirus (KSHV). We tested whether KSHV-seropositive individuals or cases of classic KS (cKS), which typically originates in the leg, had differing delayed-type hypersensitivity (DTH) in the forearm or leg. METHODS: Mantoux DTH with three antigens (Candida, tetanus, PPD) was performed on the forearm and leg of 15 cKS cases, 14 KSHV-positives without KS, and 15 KSHV-negative controls. The diameters of induration responses were compared by group and body site. RESULTS: Leg DTH was greater than forearm DTH among controls (mean difference 5.6 mm, P\ubc0.0004), whereas this was not observed in cKS cases ( 2.2 mm, P\ubc0.32) or KSHV-positives (0.5 mm, P\ubc0.56). Leg-minus-forearm DTH difference was greater in controls compared with cKS cases (P\ubc0.004) and KSHV-positives (P\ubc0.002). Leg-plus-forearm DTH was similar in controls (mean 28.2 mm) and cKS cases (24.5 mm, P\ubc0.60), but it was reduced in KSHV-positives (11.8 mm, P\ubc0.02), particularly in the leg (P\ubc0.004) and marginally in the forearm (P\ubc0.07). CONCLUSION: KS cases had weaker DTH only in the leg, whereas both body sites appeared weaker in KSHV-positives without KS. Both systemic and regional immune alterations may influence the development of this malignancy

Maternal hormone levels among populations at high and low risk of testicular germ cell cancer

Ethnic differences in maternal oestrogen levels have been suggested as explaining the significantly higher risk of testicular germ cell tumours (TGCT) of white men than black men in the United States. We therefore examined levels of maternal oestrogens, as well as testosterone and alphafetoprotein (AFP), in 150 black and 150 white mothers in the Collaborative Perinatal Project. Serum levels of estradiol (total, free and bioavailable), estriol, testosterone (total, free and bioavailable), sex hormone binding globulin (SHBG), and AFP were examined during first and third trimesters. We found that the black mothers, rather than the white mothers, had significantly higher estradiol levels in first trimester (P=0.05). Black mothers also had significantly higher levels of all testosterone (P<0.001) and AFP (P<0.001) in both trimesters. In addition, the ratios of sex hormones (estradiol/testosterone) were significantly lower among black mothers. These findings provide little support to the oestrogen hypothesis, but are consistent with higher levels of testosterones and/or AFP being associated with reduced risk of TGCT; alternatively, lower oestrogen/androgen ratios may be associated with reduced risk

Risk of testicular germ-cell tumours in relation to childhood physical activity

The US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) case–control study of testicular germ-cell tumours (TGCTs) enrolled participants and their mothers in 2002–2005. Hours of sports or vigorous childhood physical activity per week were ascertained for three time periods; 1st–5th grades, 6th–8th grades and 9th–12th grades. Son- and mother-reports were analysed separately and included 539 control son–mother pairs and 499 case son–mother pairs. Odds ratios and 95% confidence intervals were produced. The analysis of the sons' responses found no relationship between childhood physical activity and TGCT, while the mothers' analysis found an inverse association, which was solely due to nonseminoma. Future studies should seek to validate responses further using recorded information sources such as school records

Human Herpesvirus 8 Seropositivity Among Sexually Active Adults in Uganda

Sexual transmission of human herpesvirus 8 (HHV8) has been implicated among homosexual men, but the evidence for sexual transmission among heterosexual individuals is controversial. We investigated the role of sexual transmission of HHV8 in a nationally representative sample in Uganda, where HHV8 infection is endemic and transmitted mostly during childhood.The study population was a subset of participants (n = 2681) from a population-based HIV/AIDS serobehavioral survey of adults aged 15-59 years conducted in 2004/2005. High risk for sexual transmission was assessed by questionnaire and serological testing for HIV and herpes simplex virus 2. Anti-HHV8 antibodies were measured using two enzyme immunoassays targeting synthetic peptides from the K8.1 and orf65 viral genes. The current study was restricted to 2288 sexually active adults. ORs and 95% CIs for HHV8 seropositivity were estimated by fitting logistic regression models with a random intercept using MPLUS and SAS software.The weighted prevalence of HHV8 seropositivity was 56.2%, based on 1302 seropositive individuals, and it increased significantly with age (P(trend)<0.0001). In analyses adjusting for age, sex, geography, education, and HIV status, HHV8 seropositivity was positively associated with reporting two versus one marital union (OR:1.52, 95% CI: 1.17-1.97) and each unit increase in the number of children born (OR: 1.04, 95% CI: 1.00-1.08), and was inversely associated with ever having used a condom (OR: 0.64, 95% CI: 0.45-0.89). HHV8 seropositivity was not associated with HIV (P = 0.660) or with herpes simplex virus 2 (P = 0.732) seropositivity. Other sexual variables, including lifetime number of sexual partners or having had at least one sexually transmitted disease, and socioeconomic variables were unrelated to HHV8 seropositivity.Our findings are compatible with the conclusion that sexual transmission of HHV8 in Uganda, if it occurs, is weak

Neuronal Conduction of Excitation without Action Potentials Based on Ceramide Production

International audienceBACKGROUND: Action potentials are the classic mechanism by which neurons convey a state of excitation throughout their length, leading, after synaptic transmission, to the activation of other neurons and consequently to network functioning. Using an in vitro integrated model, we found previously that peripheral networks in the autonomic nervous system can organise an unconventional regulatory reflex of the digestive tract motility without action potentials. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we used combined neuropharmacological and biochemical approaches to elucidate some steps of the mechanism that conveys excitation along the nerves fibres without action potentials. This mechanism requires the production of ceramide in membrane lipid rafts, which triggers in the cytoplasm an increase in intracellular calcium concentration, followed by activation of a neuronal nitric oxide synthase leading to local production of nitric oxide, and then to guanosine cyclic monophosphate. This sequence of second messengers is activated in cascade from rafts to rafts to ensure conduction of the excitation along the nerve fibres. CONCLUSIONS/SIGNIFICANCE: Our results indicate that second messengers are involved in neuronal conduction of excitation without action potentials. This mechanism represents the first evidence-to our knowledge-that excitation is carried along nerves independently of electrical signals. This unexpected ceramide-based conduction of excitation without action potentials along the autonomic nerve fibres opens up new prospects in our understanding of neuronal functioning

Equity in the use of antithrombotic drugs, beta-blockers and statins among Finnish coronary patients

Background Earlier studies have mainly reported the use of antithrombotic drugs, beta-blockers and statins among hospital patient populations or MI patients. This study aimed to describe the use of these drugs among middle-aged Finnish coronary patients and to identify patient groups in risk of being prescribed inadequate medication for secondary prevention of coronary heart disease. Methods One-year follow-up survey data from a random sample of a cohort of coronary patients were used along with register data linked to the survey. The response rate was 54% (n = 2650). The main outcome measures were use of antithrombotic drugs, beta-blockers and statins and the data were analysed using logistic regression analysis. Results Among men and women, respectively, 82% and 81% used beta-blockers, 95% and 89% used antithrombotic drugs, and 62% and 59% used statins. Younger men and men from higher socioeconomic groups were more likely to use statins, even after controlling for disease severity and comorbidity. In women, the age trend was reversed and no socioeconomic differences were found. Drug use increased with increased disease severity, but diabetes had only a slight effect. Conclusion The use of antithrombotic drugs and beta-blockers among Finnish coronary patients seemed to be rather appropriate and, to some extent, prescription practices of preventive medication varied according to patients' risk of coronary events. However, statin use was remarkably low among men with low socio-economic status, and there is need to improve preventive drug treatment among diabetic coronary patients.BioMed Central Open acces

Comparing methods to estimate treatment effects on a continuous outcome in multicentre randomized controlled trials: A simulation study

<p>Abstract</p> <p>Background</p> <p>Multicentre randomized controlled trials (RCTs) routinely use randomization and analysis stratified by centre to control for differences between centres and to improve precision. No consensus has been reached on how to best analyze correlated continuous outcomes in such settings. Our objective was to investigate the properties of commonly used statistical models at various levels of clustering in the context of multicentre RCTs.</p> <p>Methods</p> <p>Assuming no treatment by centre interaction, we compared six methods (ignoring centre effects, including centres as fixed effects, including centres as random effects, generalized estimating equation (GEE), and fixed- and random-effects centre-level analysis) to analyze continuous outcomes in multicentre RCTs using simulations over a wide spectrum of intraclass correlation (ICC) values, and varying numbers of centres and centre size. The performance of models was evaluated in terms of bias, precision, mean squared error of the point estimator of treatment effect, empirical coverage of the 95% confidence interval, and statistical power of the procedure.</p> <p>Results</p> <p>While all methods yielded unbiased estimates of treatment effect, ignoring centres led to inflation of standard error and loss of statistical power when within centre correlation was present. Mixed-effects model was most efficient and attained nominal coverage of 95% and 90% power in almost all scenarios. Fixed-effects model was less precise when the number of centres was large and treatment allocation was subject to chance imbalance within centre. GEE approach underestimated standard error of the treatment effect when the number of centres was small. The two centre-level models led to more variable point estimates and relatively low interval coverage or statistical power depending on whether or not heterogeneity of treatment contrasts was considered in the analysis.</p> <p>Conclusions</p> <p>All six models produced unbiased estimates of treatment effect in the context of multicentre trials. Adjusting for centre as a random intercept led to the most efficient treatment effect estimation across all simulations under the normality assumption, when there was no treatment by centre interaction.</p