Celecoxib Colorectal Bioavailability and Chemopreventive Response in Patients with Familial Adenomatous Polyposis.

Why celecoxib exerts chemopreventive activity in only some familial adenomatous polyposis (FAP) patients remains poorly understood. We conducted a phase II clinical study to identify potential predictive biomarkers for celecoxib chemopreventive activity in FAP. Twenty-seven patients with FAP completed a 6-month oral course of 400 mg of celecoxib twice a day; they underwent colonoscopies before and after celecoxib treatment to assess colorectal polyp tumor burden and to obtain normal and polyp colorectal biopsies to measure celecoxib, 13-S-hydroxyoctadecadienoic acid (13-HODE), 15-HETE, 12-HETE, and LTB4 levels by LC/MS-MS. Celecoxib levels in sera from those patients were also measured before treatment and after 2, 4, and 6 months of treatment. Nineteen of the 27 patients experienced a response to celecoxib, with a ≥ 28% reduction of colonic polyp burden on the basis of a reproducible quantitative assessment of colonoscopy results. Celecoxib levels were significantly lower in polyp tissues than in normal colorectal tissues. Celecoxib levels in sera and normal colorectal tissues were correlated in patients who experienced a response to celecoxib but not in those who did not. Among the measured lipoxygenase products, only 13-HODE levels were significantly lower in polyp tissues than in normal tissues. Our findings demonstrate the differential bioavailability of celecoxib between normal and polyp tissues and its potential effects on clinical response in patients with FAP. PREVENTION RELEVANCE: This study evaluated potential predictive biomarkers for celecoxib chemopreventive activity in patients with FAP. Our findings demonstrated the differential bioavailability of celecoxib between normal and polyp tissues and its potential effects on clinical chemopreventive response in patients with FAP. See related Spotlight, p. 205.

The Timing and Sequence of Cardiovascular Health Decline.

INTRODUCTION: Childhood declines in cardiovascular health have been linked to the development of subclinical atherosclerosis; however, less is known about the timing and sequence of the decline of the specific cardiovascular health components. The study objective is to identify the patterns of decline and associations with adulthood subclinical atherosclerosis. METHODS: Data were pooled from 5 cardiovascular cohorts. Clinical components of cardiovascular health (BMI, blood pressure, cholesterol, and blood glucose) were categorized as ideal or nonideal using American Heart Association definitions. Multitrajectory models simultaneously fitted the probability ideal for each factor. Adjusted associations between trajectory groups and carotid intima-media thickness were modeled. Data were pooled from December 1, 2015 to June 1, 2019; statistical analysis occurred between June 1, 2019 and June 1, 2020. RESULTS: This study included 9,388 individuals (55% female, 66% White). A total of 5 distinct trajectory groups were created: 1 maintained the ideal levels of all the 4 health factors, 2 had risk onset of a single factor in childhood, 1 had risk onset of multiple factors in childhood, and 1 had risk onset in adulthood. Those with childhood multiple risk onset had 8.1% higher carotid intima-media thickness (95% CI=0.067, 0.095) than those in the ideal group, childhood cholesterol risk onset had 5.9% higher carotid intima-media thickness (95% CI=0.045, 0.072), childhood BMI risk onset had 5.5% higher carotid intima-media thickness (95% CI=0.041, 0.069), and early adulthood multiple risk onset had 2.7% higher carotid intima-media thickness (95% CI=0.013, 0.041). CONCLUSIONS: Those who lost the ideal status of cardiovascular health in childhood and early adulthood had more subclinical atherosclerosis than those who retained the ideal cardiovascular health across the life course, underscoring the importance of preserving the ideal cardiovascular health beginning in childhood and continued into adulthood.

Accurate identification of neutralizing antibodies to adenovirus Ad36, -a putative contributor of obesity in humans.

BACKGROUND: In children and adults, human adenovirus serotype 36 (Ad36) is linked with increased adiposity, and important metabolic alterations. Since this property is not shared by many other human adenovirus serotypes, it is imperative to specifically identify exposure to Ad36. Although serum neutralization assay (SNA) is the gold standard to specifically detect neutralizing antibodies (NA) to Ad36, it requires 2-weeks to complete and considerable training to interpret the results. Whereas, an enzyme-immuno assay (EIA) may provide a quicker and objective determination. OBJECTIVES: Evaluate the accuracy of commercially available EIA kits to detect NA to Ad36. Modify SNA to reduce time and increase objectivity. STUDY DESIGN: Sera of 15 seropositive or 16 seronegative subjects confirmed by SNA were used to test: 1) reproducibility of SNA to detect Ad36 exposure, by repeating assays twice; 2) an EIA that detects antibodies to all human adenovirus serotypes (NS-EIA) (Abcam-108705); 3) an EIA supposedly specific for Ad36 antibody (Ad36-EIA) (MyBioSource,#MBS705802), and 4) the concordance of SNA with a novel combination of SNA and immune-staining (SN-IS) kit (Cell BioLabs,#VPK-111). RESULTS: The SNA showed exact reproducibility. NS-EIA detected adenovirus antibodies in 94% samples, confirming the non-specificity of the assay for Ad36 serotype. All seronegative samples (as determined by SNA) were false positive by Ad36-EIA. In 97% samples, SN-IS showed fidelity with Ad36-antibody status as determined by SNA. CONCLUSIONS: The available EIA kits are not specific for detecting NA to Ad36. The modified SNA with immune-staining reduces assay time and increases accuracy of detecting by reducing subjectivity.

Physician weight recommendations for overweight and obese firefighters, United States, 2011-2012.

INTRODUCTION: National guidelines state that health care professionals (HCPs) should advise patients on the importance of maintaining a healthy weight. Firefighters have high rates of obesity, and cardiovascular events are the leading cause of line-of-duty deaths in firefighters. This study assessed the association of age and body mass index (BMI) with HCP weight recommendations among male firefighters. METHODS: We used data on self-reported HCP weight recommendations and measured BMI from a 2011-2012 national sample of male firefighters (N = 1,002). HCP recommendations were recorded as no advice, maintain, gain, or lose weight, and BMI was categorized as normal (<25.0 kg/m(2)), overweight (25.0-29.9 kg/m(2)), class I obese (30.0-34.9 kg/m(2)), and class II or III obese (≥35.0 kg/m(2)). We used multinomial logistic regression to estimate the odds of receiving weight advice by age and BMI categories. RESULTS: Most firefighters (96%) reported visiting an HCP in the past year. Most (69%) firefighters and 48% of class I to III obese firefighters reported receiving no weight advice. Higher BMI predicted HCP advice to lose weight (odds ratio class I obese vs normal weight: 12.98; 95% confidence interval: 5.38-31.34). Younger firefighters were less likely to receive weight loss advice than older firefighters, except among those who were class II or III obese. CONCLUSIONS: HCPs are important sources of health information for firefighters. Overweight and obese firefighters, particularly those who are younger, do not consistently receive HCP advice to lose weight. This marks a missed opportunity to prevent further weight gain and reduce obesity-related health outcomes.

Adiposity predicts self-reported frequency of poor health days among male firefighters.

OBJECTIVE: Quantify the association between adiposity and frequency of self-reported poor health days among male firefighters. METHODS: Measures were taken for body mass index, waist circumference, and percentage of body fat. Firefighters self-reported the outcome of the number of poor health days in the past 30 days. Zero-inflated negative binomial models and fractional polynomial plots were used to determine the impact of adiposity on the frequency of self-reported poor health days. RESULTS: Body mass index (rate ratio [RR]: 1.037; 95% confidence interval [CI]: 1.003 to 1.073), waist circumference (RR: 1.012; 95% CI: 0.999 to 1.030), and percentage of body fat (RR: 1.021; 95% CI: 0.999 to 1.041) were associated with self-reported poor health days. CONCLUSIONS: Adiposity is positively associated with frequency of self-reported poor health days among male firefighters. Future efforts to improve health among firefighters should emphasize reductions in adiposity.

Dietary mutagen exposure and risk of pancreatic cancer.

To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. A total of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (+/-5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases than controls showed a preference to well-done pork, bacon, grilled chicken, and pan-fried chicken, but not to hamburger and steak. Cases had a higher daily intake of food mutagens and mutagenicity activity (revertants per gram of daily meat intake) than controls did. The daily intakes of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP), as well as the mutagenic activity, were significant predictors for pancreatic cancer (P = 0.008, 0.031, and 0.029, respectively) with adjustment of other confounders. A significant trend of elevated cancer risk with increasing DiMeIQx intake was observed in quintile analysis (P(trend) = 0.024). A higher intake of dietary mutagens (those in the two top quintiles) was associated with a 2-fold increased risk of pancreatic cancer among those without a family history of cancer but not among those with a family history of cancer. A possible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to PhIP and BaP, P(interaction) = 0.09 and 0.099, respectively. These data support the hypothesis that dietary mutagen exposure alone and in interaction with other factors contribute to the development of pancreatic cancer.

Recommendations to develop an intervention for Japanese youth on weight management.

In the last 20 years the average change in BMI among Japanese youth is minimal, but significant changes appear when the categories of overweight/obesity and underweight are investigated within gender. Now intervention programs for Japanese youth on weight management need to be developed. To address the issue, there are a series of steps that could be undertaken utilizing theory of behavior change. Using the Transtheoretical Model-Stages of Change as the health promotion theory an intervention could be developed that would tailor messages to the level of the stage of readiness to weight change that exists among youth. Different aspects of the intervention could be developed and targeted to groups of youth by their needs. To assist with planning and development of the intervention principles of Intervention Mapping could be used to guide development using data from a needs assessment survey to: a) determine youths' knowledge, attitudes and beliefs about body size, b) determine youth's barriers to change in body size, c) determine parental knowledge, attitudes and beliefs about body size, d) determine parental barriers to change in youth body size, e) determine the prevalence of health problems from low and high BMI of young females and males, f) determine which youth are at risk-rural/urban areas, socioeconomic status.