Background Oral cancer is the sixth most common cancer with a five-year survival rate of approximately 60%. Presently there are no scientifically credible early detection techniques beyond conventional clinical oral examination. The goal of this study is to validate if the 7 mRNAs and 3 proteins previously reported biomarkers are capable of discriminating patients with oral squamous cell carcinomas (OSCC) from healthy subjects in independent cohorts and by a National Cancer Institute (NCI)- Early Detection Research Network (EDRN) Biomarker Reference Laboratory (BRL). Methods 395 subjects from 5 independent cohorts based on case-controlled design were investigated by 2 independent laboratories, UCLA discovery laboratory and NCI-EDRN Biomarker Reference Laboratory (BRL). Results Expression of all 7 mRNA and 3 protein markers was increased in OSCC versus controls in all 5 cohorts. With respect to individual marker performance across the 5 cohorts, the increase in IL-8 and SAT were statistically significant and remained top performers across different cohorts in terms of sensitivity and specificity. A previously identified multiple marker model demonstrated an area under the receiver operating characteristic (ROC)-curve for prediction of OSCC status ranging from of 0.74 to 0.86 across the cohorts. Conclusions The validation of these biomarkers demonstrated their feasibility in the discrimination of OSCC from healthy controls. Established assay technologies are robust enough to perform independently. Individual cutoff values for each of these markers and for the combined predictive model need to be further defined in large clinical studies. Impact Salivary proteomic and transcriptomic biomarkers can discriminate oral cancer from control subjects.

Background and Purpose Regular physical activity is an important recommendation for stroke prevention. We compared the associations of self-reported physical activity (PA) with incident stroke in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Methods REGARDS recruited 30,239 US blacks (42%) and whites, aged ≥45 with follow-up every six months for stroke events. Excluding those with prior stroke, analysis involved27,348participants who reported their frequency of moderate-vigorous intensity PA at baseline according to three categories: none (physical inactivity), 1–3 times/week and ≥ 4 times/week. Stroke and TIA cases were identified during an average of 5.7 years of follow-up. Cox proportional hazards models were constructed to examine whether self-reported PA was associated with risk of incident stroke. Results Physical inactivity was reported by 33% of participants and was associated with a hazard ratio (HR) of 1.20 ([95% confidence intervals 1.02–1.42], p = 0.035). Adjustment for demographic and socioeconomic factors did not affect HR, but further adjustment for traditional stroke risk factors (diabetes, hypertension, body mass index, alcohol use and smoking) partially attenuated this risk (HR 1.14 [0.95–1.37], p = 0.17). There was no significant association between PA frequency and risk of stroke by sex groups although there was a trend towards increased risk for men reporting PA 0–3 times a week compared to 4 or more times a week. Conclusions Self-reported low PA frequency is associated with increased risk of incident stroke. Any effect of PA is likely to be mediated through reducing traditional risk factors.

A US national sample of 20,962 participants (57% women, 44% blacks) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study provided general population estimates for ECG abnormalities among black and white men and women. Participants were recruited during 2003–2007 by random selection from a commercially available nationwide list, with oversampling of blacks and persons from the stroke belt for a cooperation rate of 49%. Measurement of risk factors and 12-lead ECGs (centrally coded using Minnesota Code criteria) showed 28% had at least one major ECG abnormality. Prevalence of abnormalities was higher (35%+) for those 65 years and older with no differences between blacks and whites. However, among men less than 65 years, blacks had more major abnormalities than whites, most notably for atrial fibrillation, major Q waves and left ventricular hypertrophy (LVH). Men generally had more ECG abnormalities than women. The most common ECG abnormalities were T-wave abnormalities. Average heart rate corrected QT interval was longer in women than men, similar in whites and blacks and increased with age, whereas the average heart rate was higher in women than men and in blacks than whites and decreased with age. The prevalence of ECG abnormalities was related to hypertension, diabetes, blood pressure level and age. In conclusion, black men and women in the US have a significantly higher prevalence of ECG abnormalities than whites at ages 45–64 but these proportions, although larger, tend to equalize or reverse after age 65.

Higher saturated fat intake is significantly associated with the presence of high albuminuria, but neither total nor other subtypes of dietary fat are associated with high albuminuria or eGFR <60 mL · min(-1) · 1.73 m(-2).

Objectives: Obese cats show many similarities to obese people, including insulin resistance and an increased diabetes risk. However, atherosclerosis and cardiovascular disease are not seen in cats. In people, they are associated with the development of an inflammatory response, which, we hypothesized, does not occur in cats. Design and Methods: Twenty neutered cats of equal gender distribution were allowed to gain weight by offering food ad libitum and were examined before and at 10, 30, 60, and 100% weight gain. All cats reached 60% of weight gain, 12 cats gained 100 % in 12 months. Results: Fat was equally distributed between subcutaneous and visceral depots. Insulin-independent glucose uptake increased and insulin sensitivity decreased with increasing adiposity. However, baseline glucose concentrations were unchanged suggesting a decrease in EGP. Inflammatory cytokines (Il-1, IL-6, TNFa) and catalase, superoxide dismutase, glutathione peroxidase did not change. Insulin, proinsulin, and leptin were positively and adiponectin negatively correlated with adiposity. Heat production increased with obesity, but became less when body weight gain was > 60 %. Conclusions: This indicates that metabolism adapts more appropriately to the higher intake of calories in the initial phase of obesity but slows at higher body fat content. This likely contributes to the difficulty to lose weight.

Objective To examine the association between prolongation of heart rate–corrected QT interval (QTc) with incident stroke. Background Unlike cardiovascular morbidity and mortality, little is known about the relationship between QTc and risk of stroke. Methods A total of 27,411 participants aged ≥ 45 years without prior stroke from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study were included in this analysis. QTc was calculated using Framingham formula (QTcFram). Stroke cases were identified and adjudicated during up to 8.2 years of follow-up (median 5.1 years). Results The risk of incident stroke in study participants with prolonged QTcFram was almost three times the risk in those with normal QTcFram [HR (95% CI): 2.88 (2.12, 3.92), p<0.0001]. After adjustment for demographics (age, race, sex), traditional stroke risk factors (antihypertensive medication use, systolic blood pressure, current smoking, diabetes, left ventricular hypertrophy, atrial fibrillation, prior cardiovascular disease), warfarin use, aspirin use, QRS duration and use of QT-prolonging drugs, the risk of stroke remained significantly high [HR (95% CI): 1.67 (1.16, 2.41), p=0.0061)], and was consistent across several subgroups of REGARDS participants. Similar results were obtained when the risk of stroke was estimated per 1-standard deviation increase in QTcFram, [HR (95% CI): 1.12 (1.03, 1.21), p=0.0053 in multivariable-adjusted model], and when other QTc correction formulas including Hodge’s, Bazett’s and Fridericia’s were used. Conclusions QTc prolongation is associated with a significantly increased risk of incident stroke independent of traditional stroke risk factors. Examining the risk of stroke associated with QT-prolonging drugs may be warranted.

Among middle-aged and older adults, the addition of CRP was most informative among underweight and normal-weight individuals, not the obese. This negated our hypothesis that increased levels of CRP would differentiate individuals at higher mortality risk due to excess adiposity.

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