The Immune Landscapes of Polypoid and Nonpolypoid Precancerous Colorectal Lesions.

Little is known about the immunoediting process in precancerous lesions. We explored this aspect of benign colorectal adenomas with a descriptive analysis of the immune pathways and immune cells whose regulation is linked to the morphology and size of these lesions. Two series of polypoid and nonpolypoid colorectal adenomas were used in this study: 1) 84 samples (42 lesions, each with matched samples of normal mucosa) whose gene expression data were used to quantify the tumor morphology- and size-related dysregulation of immune pathways collected in the Molecular Signature Database, using Gene Set Enrichment Analysis; 2) 40 other lesions examined with immunohistochemistry to quantify the presence of immune cells in the stromal compartment. In the analysis of transcriptomic data, 429 immune pathways displayed significant differential regulation in neoplasms of different morphology and size. Most pathways were significantly upregulated or downregulated in polypoid lesions versus nonpolypoid lesions (regardless of size). Differential pathway regulation associated with lesion size was observed only in polypoid neoplasms. These findings were mirrored by tissue immunostaining with CD4, CD8, FOXP3, MHC-I, CD68, and CD163 antibodies: stromal immune cell counts (mainly T lymphocytes and macrophages) were significantly higher in polypoid lesions. Certain markers displayed significant size-related differences regardless of lesion morphology. Multivariate analysis of variance showed that the marker panel clearly discriminated between precancerous lesions of different morphologies and sizes. Statistical analysis of immunostained cell counts fully support the results of the transcriptomic data analysis: the density of infiltration of most immune cells in the stroma of polypoid precancerous lesions was significantly higher than that observed in nonpolypoid lesions. Large neoplasms also have more immune cells in their stroma than small lesions. Immunoediting in precancerous colorectal tumors may vary with lesion morphology and stage of development, and this variability could influence a given lesion's trajectory to cancer

A Strange Association Between A Rectum- Infiltrating / Metastatic Dedifferentiated Chordoma And Schmidt's Syndrome

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Television, adiposity, and cardiometabolic risk in children and adolescents

Background: It is largely unknown how TV use relates to depot-specific adiposity or cardiometabolic risk in children. Purpose: To examine relationships between having a TV in the bedroom and TV viewing time with total fat mass, abdominal subcutaneous and visceral adiposity, and cardiometabolic risk in children and adolescents. Methods: A cross-sectional study of 369 children and adolescents aged 5-18 years was conducted (2010-2011; analysis 2011-2012). Waist circumference; resting blood pressure; fasting triglycerides, high-density lipoprotein cholesterol [HDL-C] and glucose; fat mass by dual-energy x-ray absorptiometry; and abdominal subcutaneous and visceral adiposity by MRI were assessed. Cardiometabolic risk was defined as three or more risk factors including adverse levels of waist circumference, blood pressure, triglycerides, HDL-C, and glucose. Logistic regression analysis was used to compute ORs of high fat mass; subcutaneous and visceral adipose tissue mass (top age-adjusted quartile); and cardiometabolic risk, based on self-reported TV present in the bedroom and TV viewing time, controlling for age, gender, ethnicity, moderate-to-vigorous physical activity level, and unhealthy diet. Results: In multivariable models, presence of a TV in the bedroom and TV viewing time were associated with (p<0.05) higher odds of high waist circumference (OR=1.9–2.1); fat mass (OR=2.0–2.5); and subcutaneous adiposity (OR=2.1–2.9), whereas viewing TV ≥5 hours/day was associated with high visceral adiposity (OR=2.0). Having a TV in the bedroom was associated with elevated cardiometabolic risk (OR=2.9) and high triglycerides (OR=2.0). Conclusions Having a bedroom TV and TV viewing time were related to high waist circumference, fat mass, and abdominal subcutaneous adiposity. TV viewing time was related to visceral adiposity, and bedroom TV was related to cardiometabolic risk in children, controlling for moderate-to-vigorous physical activity and an unhealthy diet

BMI percentiles for the identification of abdominal obesity and metabolic risk in children and adolescents : evidence in support of the CDC 95th percentile

Objectives:Body mass index (BMI) percentiles have been routinely and historically used to identify elevated adiposity. The aim of this study was to investigate the optimal Centers for Disease Control and Prevention (CDC) BMI percentile that predicts elevated visceral adipose tissue (VAT), fat mass and cardiometabolic risk in a biracial sample of children and adolescents. Participants and Methods: This cross-sectional analysis included 369 white and African-American children (5-18 years). BMI was calculated using height and weight and converted to BMI percentiles based on CDC growth charts. Receiver operating characteristic curve analysis identified the optimal (balance of sensitivity and specificity) BMI percentile to predict the upper quartile of age-adjusted VAT (measured by magnetic resonance imaging), age-adjusted fat mass (measured by dual-energy X-ray absorptiometry) and elevated cardiometabolic risk (≥2 of high glucose, triglycerides and blood pressure, and low high-density lipoprotein cholesterol) for each race-by-sex group. Results: The optimal CDC BMI percentile to predict those in the top quartile of age-adjusted VAT, age-adjusted fat mass and elevated cardiometabolic risk were the 96th, the 96th and the 94th percentiles, respectively, for the sample as a whole. Sensitivity and specificity was satisfactory (>0.70) for VAT and fat mass. Compared to VAT and fat mass, there was a lower overall accuracy of the optimal percentile in identifying those with elevated cardiometabolic risk. Conclusions: The present findings support the utility of the 95th CDC BMI percentile as a useful threshold for the prediction of elevated levels of VAT, fat mass and cardiometabolic risk in children and adolescents

The descriptive epidemiology of sitting among US adults, NHANES 2009/2010

Objectives: Using NHANES 2009/2010, to describe the amount of time a representative sample of the U.S. population spends sitting by age, sex, ethnicity, education, and body mass index. Design: Cross-sectional analysis. Methods: Participants (n= 5911, ≥20 years) self-reported demographic variables and the amount of time they spend sitting on a typical day. Body mass index was calculated from measured height and weight. Results: Mean self-reported sitting time was 285. min/day for males and 281. min/day for females. Mexican-Americans reported sitting less than both non-Hispanic Whites and non-Hispanic Blacks (all p <0.0001). Non-Hispanic White males reported sitting more than non-Hispanic Black males, while Non-Hispanic White females reported sitting more than Other Hispanic females (both p <0.0001). No significant differences were found between sexes in any age group. There was a trend for increased sitting time with increasing age for females (p for trend = 0.0045), for all Mexican-American and Hispanic participants and non-Hispanic Black males (all p ≤ 0.006) and with increasing education (p for trend <0.0001). At the College Graduate level, females reported sitting less than males (p < 0.0001). Obese females reported sitting more than normal weight and overweight females (p = 0.0008). There were no significant differences in sitting time by body mass index for males. Conclusions: Self-reported sitting time differed by ethnicity, age group, education and body mass index but there was no overall difference by sex. These results represent the most up to date prevalence of self-reported sitting for the US adult population. Certain groups should be targeted to reduce sitting time, for example those with higher educational attainment and obese females

Evidence for local control of gene expression in the epidermal differentiation complex

The epidermal differentiation complex (EDC), located on chromosomal band 1q21, consists of at least 43 genes that are expressed during keratinocyte differentiation. Indicative of a role for chromatin structure in tissue specificity of EDC gene expression, we identified an inverse correlation between expression and DNA methylation for two EDC genes (S100A2 and S00A6) in human keratinocytes and fibroblasts. 5-azacytidine (5AC) and sodium butyrate (NaB) are two agents known to promote ‘open’ chromatin structure. To explore the relationship between chromatin structure and keratinocyte differentiation, we treated normal human keratinocytes (NHK) with 5AC or NaB, or with protocols known to promote their terminal differentiation. We then measured the steady-state mRNA levels for several S100 genes, small proline rich region-1, -2, and -3, loricrin, and involucrin by Northern blotting. 5AC and NaB each markedly increased expression of SPRR1/2 and involucrin in NHK. In contrast, expression of S100A2 was reduced by both agents, and by induction of keratinocyte differentiation. Moreover, while the clustered EDC genes displayed a general tendency to be expressed in epithelial cells, they displayed different patterns of cell type-specific expression. These results indicate that local, gene-specific factors play an important role in the regulation of EDC gene expression in the keratinocyte lineage and during keratinocyte terminal differentiation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71593/1/j.1600-0625.2002.110503.x.pd

Measurement of the proton and deuteron structure functions, F2p and F2d, and of the ratio sigma(L)/sigma(T)

The muon-proton and muon-deuteron inclusive deep inelastic scattering cross sections were measured in the kinematic range 0.002 < x < 0.60 and 0.5 < Q2 < 75 GeV2 at incident muon energies of 90, 120, 200 and 280 GeV. These results are based on the full data set collected by the New Muon Collaboration, including the data taken with a small angle trigger. The extracted values of the structure functions F2p and F2d are in good agreement with those from other experiments. The data cover a sufficient range of y to allow the determination of the ratio of the longitudinally to transversely polarised virtual photon absorption cross sections, R= sigma(L)/sigma(T), for 0.002 < x < 0.12 . The values of R are compatible with a perturbative QCD prediction; they agree with earlier measurements and extend to smaller x.Comment: In this replacement the erroneously quoted R values in tables 3-6 for x>0.12, and R1990 values in tables 5-6 for all x, have been corrected, and the cross sections in tables 3-4 have been adapted. Everything else, including the structure functions F2, remained unchanged. 22 pages, LateX, including figures, with two .sty files, and three separate f2tab.tex files for the F2-tables. Accepted for publication in Nucl.Phys.B 199