Long-term burden of increased body mass index from childhood on adult dyslipidemia: the i3C Consortium study

Background: Data are limited regarding the association of cumulative burden and trajectory of body mass index (BMI) from early life with adult lipid disorders. Methods: The study cohort consisted of 5195 adults who had BMI repeatedly measured 4 to 21 times from childhood and had blood lipid measurements of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) and information on lipid-lowering medications in the last adult survey. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI. Results: Participants with dyslipidemia, high LDL-C, low HDL-C and high TG had consistently and significantly higher BMI levels from childhood to adulthood compared to those with normal lipid levels. After adjusting for age, race, sex, and cohort, increased risk of adult dyslipidemia was significantly associated with higher values of childhood BMI, adulthood BMI, total AUC and incremental AUC, with odds ratio (95% confidence interval) = 1.22 (1.15-1.29), 1.85 (1.74-1.97), 1.61 (1.52-1.71), and 1.59 (1.50-1.69), respectively, and p Conclusions: Adults with dyslipidemia versus normal lipid levels have consistently higher levels and distinct life-course trajectories of BMI, suggesting that the impact of excessive body weight on dyslipidemia originates in early life

TUNEL – an efficient prognosis predictor of salivary malignancies

Biological markers are necessary for predicting prognosis of salivary malignancies and better understanding the pathogenesis of salivary cancer. We analysed terminal deoxynucleotidyl transferase (TdT)-mediated biotinylated deoxyuridine-triphosphate (dUTP)-biotin nick-end labelling (TUNEL), p53 and Ki67 expression in 66 patients with malignant salivary tumours by immonohistochemistry, and correlated the data with survival, disease-free survival, tumour grade, stage, and local and distant metastasis. TUNEL efficiently predicted poor prognosis in salivary malignancies. The 5-year (5Y) survival probability dropped significantly with the level of TUNEL staining (from 83% in negatively stained tumours to 57 and 24% in TUNEL positively stained levels 1 and 2, respectively), (P=0.042). Extensive Ki67 staining (in addition to TUNEL) reduced the 5Y-survival rate even further and addition of positively stained p53 dropped the 5Y-survival rate to 0. The correlation rates between TUNEL and Ki67 was 58% (P=0.0001), and between TUNEL and p53 it was 50% (P=0.035). Concurrently, TUNEL correlated with metastasis, extracapsular spread, grade and stage. The correlation between TUNEL, p53 and Ki67 staining and survival probabilities, and the pathological grade, stage and metastasis spread of salivary malignancies makes this a highly effective tool in patient follow-up and prognosis

Relation of Blood Pressure in Childhood to Self-Reported Hypertension in Adulthood: The International Childhood Cardiovascular Cohort Consortium

Blood pressure (BP) tracking (maintaining a BP percentile) across life is not well defined but is important in predicting which children will become hypertensive adults. We computed BP tracking in subjects with BP measured in childhood and adulthood and performed logistic regression to determine the ability of childhood BP to predict adult hypertension (N=5035, 46.7 years, 74.2% white, 17.7% black; 39.6% male). Prevalence of hypertension was 29%. Correlations between systolic BP for child and adolescent were r=0.48; for adolescent and young adult were r=0.40, and for child and young adult were r=0.24 (all P<0.0001). Participants self-reporting adult hypertension were less likely to be white (38.7% black, 27.6% white, 20.9% other; P<0.0001) and female (26.4% females, 32.9% male, P<0.0001). Participants with adult hypertension were more likely to have higher BP and adiposity by age 10 years and abnormal lipids and glucose by age 16 years. There was a graded increase in the frequency of self-reported adult hypertension across the BP change groups, even within the persistently normotensive group (X-2<0.0001) from 19% in children with a systolic BP% persistently below the median to 80% for individuals with elevated BP in both childhood and adolescence. Although our precision to predict which individual child is at risk of adult BP-related cardiovascular disease is weak, an increase in systolic BP and body mass index percentile from childhood to adolescence should signal a need for lifestyle intervention to prevent future sustained hypertension-related cardiovascular disease

Long-Term Burden of Increased Body Mass Index from Childhood on Adult Dyslipidemia: The i3C Consortium Study

Background: Data are limited regarding the association of cumulative burden and trajectory of body mass index (BMI) from early life with adult lipid disorders. Methods: The study cohort consisted of 5195 adults who had BMI repeatedly measured 4 to 21 times from childhood and had blood lipid measurements of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) and information on lipid-lowering medications in the last adult survey. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI. Results: Participants with dyslipidemia, high LDL-C, low HDL-C and high TG had consistently and significantly higher BMI levels from childhood to adulthood compared to those with normal lipid levels. After adjusting for age, race, sex, and cohort, increased risk of adult dyslipidemia was significantly associated with higher values of childhood BMI, adulthood BMI, total AUC and incremental AUC, with odds ratio (95% confidence interval) = 1.22 (1.15-1.29), 1.85 (1.74-1.97), 1.61 (1.52-1.71), and 1.59 (1.50-1.69), respectively, and p Conclusions: Adults with dyslipidemia versus normal lipid levels have consistently higher levels and distinct life-course trajectories of BMI, suggesting that the impact of excessive body weight on dyslipidemia originates in early life.</p

Time esophageal pH < 4 overestimates the prevalence of pathologic esophageal reflux in subjects with gastroesophageal reflux disease treated with proton pump inhibitors

<p>Abstract</p> <p>Background</p> <p>A Stanford University study reported that in asymptomatic GERD patients who were being treated with a proton pump inhibitor (PPI), 50% had pathologic esophageal acid exposure.</p> <p>Aim</p> <p>We considered the possibility that the high prevalence of pathologic esophageal reflux might simply have resulted from calculating acidity as time pH < 4.</p> <p>Methods</p> <p>We calculated integrated acidity and time pH < 4 from the 49 recordings of 24-hour gastric and esophageal pH from the Stanford study as well as from another study of 57 GERD subjects, 26 of whom were treated for 8 days with 20 mg omeprazole or 20 mg rabeprazole in a 2-way crossover fashion.</p> <p>Results</p> <p>The prevalence of pathologic 24-hour esophageal reflux in both studies was significantly higher when measured as time pH < 4 than when measured as integrated acidity. This difference was entirely attributable to a difference between the two measures during the nocturnal period. Nocturnal gastric acid breakthrough was not a useful predictor of pathologic nocturnal esophageal reflux.</p> <p>Conclusion</p> <p>In GERD subjects treated with a PPI, measuring time esophageal pH < 4 will significantly overestimate the prevalence of pathologic esophageal acid exposure over 24 hours and during the nocturnal period.</p

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

OAS1 Polymorphisms Are Associated with Susceptibility to West Nile Encephalitis in Horses

West Nile virus, first identified within the United States in 1999, has since spread across the continental states and infected birds, humans and domestic animals, resulting in numerous deaths. Previous studies in mice identified the Oas1b gene, a member of the OAS/RNASEL innate immune system, as a determining factor for resistance to West Nile virus (WNV) infection. A recent case-control association study described mutations of human OAS1 associated with clinical susceptibility to WNV infection. Similar studies in horses, a particularly susceptible species, have been lacking, in part, because of the difficulty in collecting populations sufficiently homogenous in their infection and disease states. The equine OAS gene cluster most closely resembles the human cluster, with single copies of OAS1, OAS3 and OAS2 in the same orientation. With naturally occurring susceptible and resistant sub-populations to lethal West Nile encephalitis, we undertook a case-control association study to investigate whether, similar to humans (OAS1) and mice (Oas1b), equine OAS1 plays a role in resistance to severe WNV infection. We identified naturally occurring single nucleotide mutations in equine (Equus caballus) OAS1 and RNASEL genes and, using Fisher's Exact test, we provide evidence that mutations in equine OAS1 contribute to host susceptibility. Virtually all of the associated OAS1 polymorphisms were located within the interferon-inducible promoter, suggesting that differences in OAS1 gene expression may determine the host's ability to resist clinical manifestations associated with WNV infection

Erratum to: Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes: individual patient data (IPD) meta-analysis and health economic evaluation.

Erratum to: Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes: individual patient data (IPD) meta-analysis and health economic evaluatio