Attitudes towards colorectal cancer (CRC) and CRC screening tests among elderly Malay patients.

Science.gov (United States)

Al-Naggar, Redhwan A; Al-Kubaisy, Waqar; Yap, Bee W; Bobryshev, Yuri V; Osman, Muhamed T

2015-01-01

Colorectal cancer (CRC) is the third most common malignancy in Malaysia, where data are limited regarding knowledge and barriers in regard to CRC and screening tests. The aim of the study was to assess these parameters among Malaysians. The questionnaires were distributed in the Umra Private Hospital in Selangor. The questionnaire had four parts and covered social-demographic questions, respondent knowledge about CRC and colorectal tests, attitude towards CRC and respondentaction regarding CRC. More than half of Malay participants (total n=187) were female (57.2%) and 36.9% of them were working as professionals. The majority of the participants (93.6%) never had a CRC screening test. The study found that only 10.2% of the study participants did not consider that their chances of getting CRC were high. A high percentage of the participants (43.3%) believed that they would have good chance of survival if the cancer would be found early. About one third of the respondents did not want to do screening because of fear of cancer, and concerns of embarrassment during the procedure adversely affected attitude to CRC screening as well. Age, gender, income, family history of CRC, vegetable intake and physical activity were found to be significant determinants of knowledge on CRC. The major barriers identified towards CRC screening identified in our study were fear of pain and embarrassment. The findings have implications for understanding of similarities and differences in attitude to CRC amongst elderly patients in other cultural/ geographic regions.

Pseudomonas putida growing at low temperature shows increased levels of CrcZ and CrcY sRNAs, leading to reduced Crc-dependent catabolite repression.

Science.gov (United States)

Fonseca, Pilar; Moreno, Renata; Rojo, Fernando

2013-01-01

The Crc protein of Pseudomonas inhibits the expression of genes involved in the transport and assimilation of a number of non-preferred carbon sources when preferred substrates are available, thus coordinating carbon metabolism. Crc acts by binding to target mRNAs, inhibiting their translation. In Pseudomonas putida, the amount of free Crc available is controlled by two sRNAs, CrcY and CrcZ, which bind to and sequester Crc. The levels of these sRNAs vary according to metabolic conditions. Pseudomonas putida grows optimally at 30°C, but can also thrive at 10°C. The present work shows that when cells grow exponentially at 10°C, the repressive effect of Crc on many genes is significantly reduced compared with that seen at 30°C. Total Crc levels were similar at both temperatures, but those of CrcZ and CrcY were significantly higher at 10°C. Therefore, Crc-mediated repression may, at least in part, be reduced at 10°C because the fraction of Crc protein sequestered by CrcZ and CrcY is larger, reducing the amount of free Crc available to bind its targets. This may help P. putida to face cold stress. The results reported might help understanding the behaviour of this bacterium in bioremediation or rhizoremediation strategies at low temperatures. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

Childhood and adolescent energy restriction and subsequent colorectal cancer risk: results from the Netherlands Cohort Study.

Science.gov (United States)

Hughes, Laura A E; van den Brandt, Piet A; Goldbohm, R Alexandra; de Goeij, Anton F P M; de Bruïne, Adriaan P; van Engeland, Manon; Weijenberg, Matty P

2010-10-01

Energy restriction during childhood and adolescence is suggested to lower colorectal cancer (CRC) risk. We investigated this in the Netherlands Cohort Study. Information on diet and other risk factors was collected by a baseline questionnaire in 1986 when cohort members were 55-69 years of age (n = 120 852). Three indicators of early life exposure to energy restriction were assessed: father's employment status during the Economic Depression (1932-40), place of residence during Second World War years (1940-44) and the 'Hunger Winter' (1944-45), a severe famine. Using the case-cohort approach, incidence rate ratios (RRs) and 95% confidence intervals (CIs) were calculated for total colorectal, proximal colon, distal colon, rectosigmoid and rectal cancers, according to the three time periods of energy restriction. After 16.3 years of follow-up, 2573 cases were available for multivariate analyses. Men who lived in a western city during the Hunger Winter and therefore exposed to the highest degree of energy restriction, had a lower risk of developing CRC (RR: 0.81, 95% CI: 0.68-0.98), and tumours of the proximal colon (RR: 0.72, 95% CI: 0.54-0.96) and rectum (RR: 0.71, 95% CI: 0.53-0.96). In women, non-statistically significant inverse associations were observed for tumours of the distal colon, rectosigmoid and rectum. Inverse associations were also observed between the other two exposure times and studied endpoints, though not statistically significant. This unique observational evidence suggests that severe energy restriction during childhood and adolescence may lower CRC risk, especially in men, thus providing insight regarding the role of energy intake during early life in CRC development.

The requirement for freshly isolated human colorectal cancer (CRC) cells in isolating CRC stem cells.

Science.gov (United States)

Fan, F; Bellister, S; Lu, J; Ye, X; Boulbes, D R; Tozzi, F; Sceusi, E; Kopetz, S; Tian, F; Xia, L; Zhou, Y; Bhattacharya, R; Ellis, L M

2015-02-03

Isolation of colorectal cancer (CRC) cell populations enriched for cancer stem cells (CSCs) may facilitate target identification. There is no consensus regarding the best methods for isolating CRC stem cells (CRC-SCs). We determined the suitability of various cellular models and various stem cell markers for the isolation of CRC-SCs. Established human CRC cell lines, established CRC cell lines passaged through mice, patient-derived xenograft (PDX)-derived cells, early passage/newly established cell lines, and cells directly from clinical specimens were studied. Cells were FAC-sorted for the CRC-SC markers CD44, CD133, and aldehyde dehydrogenase (ALDH). Sphere formation and in vivo tumorigenicity studies were used to validate CRC-SC enrichment. None of the markers studied in established cell lines, grown either in vitro or in vivo, consistently enriched for CRC-SCs. In the three other cellular models, CD44 and CD133 did not reliably enrich for stemness. In contrast, freshly isolated PDX-derived cells or early passage/newly established CRC cell lines with high ALDH activity formed spheres in vitro and enhanced tumorigenicity in vivo, whereas cells with low ALDH activity did not. PDX-derived cells, early passages/newly established CRC cell lines and cells from clinical specimen with high ALDH activity can be used to identify CRC-SC-enriched populations. Established CRC cell lines should not be used to isolate CSCs.

Main: CRC101 [AT Atlas

Lifescience Database Archive (English)

Full Text Available CRC101 CRC1 Establishment of Chemical Library and Development of Protein Regulation... Technology Chemical library Tetsuo Nagano Graduate School of Pharmaceutical Sciences, The University CRC101.csml ...

CRC-113 gene expression signature for predicting prognosis in patients with colorectal cancer.

Science.gov (United States)

Nguyen, Minh Nam; Choi, Tae Gyu; Nguyen, Dinh Truong; Kim, Jin-Hwan; Jo, Yong Hwa; Shahid, Muhammad; Akter, Salima; Aryal, Saurav Nath; Yoo, Ji Youn; Ahn, Yong-Joo; Cho, Kyoung Min; Lee, Ju-Seog; Choe, Wonchae; Kang, Insug; Ha, Joohun; Kim, Sung Soo

2015-10-13

Colorectal cancer (CRC) is the third leading cause of global cancer mortality. Recent studies have proposed several gene signatures to predict CRC prognosis, but none of those have proven reliable for predicting prognosis in clinical practice yet due to poor reproducibility and molecular heterogeneity. Here, we have established a prognostic signature of 113 probe sets (CRC-113) that include potential biomarkers and reflect the biological and clinical characteristics. Robustness and accuracy were significantly validated in external data sets from 19 centers in five countries. In multivariate analysis, CRC-113 gene signature showed a stronger prognostic value for survival and disease recurrence in CRC patients than current clinicopathological risk factors and molecular alterations. We also demonstrated that the CRC-113 gene signature reflected both genetic and epigenetic molecular heterogeneity in CRC patients. Furthermore, incorporation of the CRC-113 gene signature into a clinical context and molecular markers further refined the selection of the CRC patients who might benefit from postoperative chemotherapy. Conclusively, CRC-113 gene signature provides new possibilities for improving prognostic models and personalized therapeutic strategies.

Slender CRC Columns

DEFF Research Database (Denmark)

Aarup, Bendt; Jensen, Lars Rom; Ellegaard, Peter

2005-01-01

CRC is a high-performance steel fibre reinforced concrete with a typical compressive strength of 150 MPa. Design methods for a number of structural elements have been developed since CRC was invented in 1986, but the current project set out to further investigate the range of columns for which...

Mining, Validation, and Clinical Significance of Colorectal Cancer (CRC)-Associated lncRNAs.

Science.gov (United States)

Sun, Xiangwei; Hu, Yingying; Zhang, Liang; Hu, Changyuan; Guo, Gangqiang; Mao, Chenchen; Xu, Jianfeng; Ye, Sisi; Huang, Guanli; Xue, Xiangyang; Guo, Aizhen; Shen, Xian

2016-01-01

Colorectal cancer (CRC) is one of the deadliest tumours, but its pathogenesis remains unclear. The involvement of differentially expressed long non-coding RNAs (lncRNAs) in CRC tumorigenesis makes them suitable tumour biomarkers. Here, we screened 150 cases of CRC and 85 cases of paracancerous tissues in the GEO database for differentially expressed lncRNAs. The levels of lncRNA candidates in 84 CRC and paracancerous tissue samples were validated by qRT-PCR and their clinical significance was analyzed. We identified 15 lncRNAs with differential expression in CRC tumours; among them, AK098081 was significantly up-regulated, whereas AK025209, BC040303, BC037331, AK026659, and CR749831 were down-regulated in CRC. In a receiver operating characteristic curve analysis, the area under the curve for the six lncRNAs was 0.914. High expression of AK098081 and low expression of BC040303, CR749831, and BC037331 indicated poor CRC differentiation. CRC patients with lymph node metastasis had lower expression of BC037331. In addition, the group with high AK098081 expression presented significantly lower overall survival and disease-free survival rates than the low-expression group, confirming AK098081 as an independent risk factor for CRC patients. In conclusion, we have identified multiple CRC-associated lncRNAs from microarray expression profiles that can serve as novel biomarkers for the diagnosis and prognosis of CRC.

A dietary pattern that is associated with C-peptide and risk of colorectal cancer in women.

Science.gov (United States)

Fung, Teresa T; Hu, Frank B; Schulze, Matthias; Pollak, Michael; Wu, Tianying; Fuchs, Charles S; Giovannucci, Edward

2012-06-01

Higher serum C-peptide concentrations have shown to be associated with an increased risk of colorectal cancer (CRC). Therefore, we used diet information to identify food groups that correlated with fasting serum concentrations of C-peptide and assess the association of this dietary pattern and CRC risk. Major food contributors to fasting C-peptide concentrations were identified with stepwise linear regression in a subsample (n = 833) of women from a large cohort. We then summed the consumption frequency of the major food contributors to form a C-peptide dietary pattern for the entire cohort (n = 66,714). Risk for CRC was computed using Cox proportional hazard model with the C-peptide dietary pattern score as the predictor. In up to 20 years of follow-up, we ascertained 985 cases of CRC and 758 colon cancer. After adjusting for confounders, the C-peptide dietary pattern, characterized by higher meat, fish, and sweetened beverage intake, but lower coffee, high fat dairy, and whole grains intake, showed direct association with CRC risk (RR comparing extreme quintiles = 1.29, 95 % CI = 1.05-1.58, p trend = 0.048). The same comparison was slightly stronger for colon cancer (RR = 1.35, 95 % CI = 1.07-1.70, p trend = 0.009). In stratified analysis, there was no association between the C-peptide dietary pattern and colon cancer among lean and active women. However, for overweight or sedentary women, RR for the same comparison was 1.58 (95 % CI = 1.20-2.07, p trend = 0.002) (p for interaction = 0.007). We derived a dietary pattern that correlated with C-peptide concentrations. This pattern was associated with an increase in colon cancer, especially among women who were overweight or sedentary.

Effect of Crc and Hfq proteins on the transcription, processing, and stability of the Pseudomonas putida CrcZ sRNA.

Science.gov (United States)

Hernández-Arranz, Sofía; Sánchez-Hevia, Dione; Rojo, Fernando; Moreno, Renata

2016-12-01

In Pseudomonas putida, the Hfq and Crc proteins regulate the expression of many genes in response to nutritional and environmental cues, by binding to mRNAs that bear specific target motifs and inhibiting their translation. The effect of these two proteins is antagonized by the CrcZ and CrcY small RNAs (sRNAs), the levels of which vary greatly according to growth conditions. The crcZ and crcY genes are transcribed from promoters PcrcZ and PcrcY, respectively, a process that relies on the CbrB transcriptional activator and the RpoN σ factor. Here we show that crcZ can also be transcribed from the promoter of the immediate upstream gene, cbrB, a weak constitutive promoter. The cbrB-crcZ transcript was processed to render a sRNA very similar in size to the CrcZ produced from promoter PcrcZ The processed sRNA, termed CrcZ*, was able to antagonize Hfq/Crc because, when provided in trans, it relieved the deregulated Hfq/Crc-dependent hyperrepressing phenotype of a ΔcrcZΔcrcY strain. CrcZ* may help in attaining basal levels of CrcZ/CrcZ* that are sufficient to protect the cell from an excessive Hfq/Crc-dependent repression. Since a functional sRNA can be produced from PcrcZ, an inducible strong promoter, or by cleavage of the cbrB-crcZ mRNA, crcZ can be considered a 3'-untranslated region of the cbrB-crcZ mRNA. In the absence of Hfq, the processed form of CrcZ was not observed. In addition, we show that Crc and Hfq increase CrcZ stability, which supports the idea that these proteins can form a complex with CrcZ and protect it from degradation by RNases. © 2016 Hernández-Arranz et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Dietary Patterns and Risk of Colorectal Cancer: Analysis by Tumor Location and Molecular Subtypes.

Science.gov (United States)

Mehta, Raaj S; Song, Mingyang; Nishihara, Reiko; Drew, David A; Wu, Kana; Qian, Zhi Rong; Fung, Teresa T; Hamada, Tsuyoshi; Masugi, Yohei; da Silva, Annacarolina; Shi, Yan; Li, Wanwan; Gu, Mancang; Willett, Walter C; Fuchs, Charles S; Giovannucci, Edward L; Ogino, Shuji; Chan, Andrew T

2017-06-01

Western and prudent dietary patterns have been associated with higher and lower risks of colorectal cancer (CRC), respectively. However, little is known about the associations between dietary patterns and specific anatomic subsites or molecular subtypes of CRC. We used multivariable Cox proportional hazards models to examine the associations between Western and prudent dietary patterns and CRC risk in the Health Professionals Follow-up Study and Nurses' Health Study. After up to 32 years of follow-up of 137,217 men and women, we documented 3260 cases of CRC. Among individuals from whom subsite data were available, we observed 1264 proximal colon, 866 distal colon, and 670 rectal tumors. Western diet was associated with an increased incidence of CRC (P trend pattern, we observed a RR of 0.86 for overall CRC (95% CI, 0.77-0.95; P trend  = .01), with similar trends at anatomic subsites. However, the trend appeared stronger among men than women. Among 1285 cases (39%) with tissue available for molecular profiling, Western diet appeared to be more strongly associated with some CRC molecular subtypes (no mutations in KRAS [KRAS wildtype] or BRAF [BRAF wildtype], no or a low CpG island methylator phenotype, and microsatellite stability), although formal tests for heterogeneity did not produce statistically significant results. Western dietary patterns are associated with an increased risk of CRC, particularly distal colon and rectal tumors. Western dietary patterns also appear more strongly associated with tumors that are KRAS wildtype, BRAF wildtype, have no or a low CpG island methylator phenotype, and microsatellite stability. In contrast, prudent dietary patterns are associated with a lower risk of CRC that does not vary according to anatomic subsite or molecular subtype. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Obesity and risk of colorectal cancer: a systematic review of prospective studies.

Directory of Open Access Journals (Sweden)

Yanlei Ma

Full Text Available BACKGROUND: Mounting evidence indicates that obesity may be associated with the risk of colorectal cancer (CRC. To conduct a systematic review of prospective studies assessing the association of obesity with the risk of CRC using meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: Relevant studies were identified by a search of MEDLINE and EMBASE databases before January 2012, with no restrictions. We also reviewed reference lists from retrieved articles. We included prospective studies that reported relative risk (RR estimates with 95% confidence intervals (CIs for the association between general obesity [measured using body mass index (BMI] or central obesity [measured using waist circumference (WC] and the risk of colorectal, colon, or rectal cancer. Approximately 9, 000, 000 participants from several countries were included in this analysis. 41 studies on general obesity and 13 studies on central obesity were included in the meta-analysis. The pooled RRs of CRC for the obese vs. normal category of BMI were 1.334 (95% CI, 1.253-1.420, and the highest vs. lowest category of WC were 1.455 (95% CI, 1.327-1.596. There was heterogeneity among studies of BMI (P<0.001 but not among studies of WC (P=0.323. CONCLUSIONS: Both of general and central obesity were positively associated with the risk of CRC in this meta-analysis.

CRC-cards for Product Modelling

DEFF Research Database (Denmark)

Hvam, Lars; Riis, Jesper; Hansen, Benjamin Loer

2003-01-01

, transportation, service and decommissioning. A main challenge when building product models is to collect and document the product related data, information and knowledge in a structured way. CRC cards are index cards (or computerized versions of these) which are used to record proposed classes, the behavior......This paper describes the CRC (class, responsibility, collaboration) modelling process for building product models. A product model is normally represented in an IT system which contains data, information and knowledge on industrial products and their life cycle properties e.g. manufacturing...... of the classes, their responsibilities, and their relationship to other classes (collaboration). CRC modelling gives an effective, low-tech method for domain-experts, programmers and users to work closely together to identify, structure, understand and document a product model. CRC cards were originally...

Upregulated STAT3 and RhoA signaling in colorectal cancer (CRC) regulate the invasion and migration of CRC cells.

Science.gov (United States)

Zhang, G-Y; Yang, W-H; Chen, Z

2016-05-01

We aimed to reveal the expression and activation of signal transducers and activators of transcription 3 (STAT3) and RhoA/Rho-associated coiled-coil forming kinase 1 (ROCK1) signaling in CRC tissues, and to investigate the regulatory role of STAT3 and RhoA signaling in the invasion and migration of colorectal cancer cells. We examined the expression of STAT3, RhoA and ROCK1 in CRC tissues with real-time PCR and Western blotting methods. And then we examined the interaction between STAT3 and RhoA/ROCK1 signaling in CRC HT-29 cells with gain-of-function and loss-of-function strategies. In addition, we determined the regulation by STAT3 and RhoA/ROCK1 on the invasion and migration of CRC HT-29 cells. Our study demonstrated a significant upregulation of RhoA and ROCK1 expression and STAT3-Y705 phosphorylation in 32 CRC specimens, compared to the 17 normal CRC tissues. Further study demonstrated there was a coordination between STAT3 and RhoA/Rock signaling in the HT-29 cells. Moreover, STAT3 knockdown or RhoA knockdown significantly repressed the migration and invasion in HT-29 cells and vice versa. STAT3 and RhoA signaling regulate the invasion and migration of CRC cells, implying the orchestrated and oncogenic roles of STAT3 and RhoA/ROCK1 signaling in CRC.

Tape Storage and CRC Protection

CERN Document Server

Ha, Karel

2014-01-01

Over 100 Petabytes of data is stored on several kind of physical support, namely disks and tapes. Data on any physical support or traveling on a data link (network, fibre channel...) can be subject to silent data corruption. A possible improvement is introducing end-to-end data integrity from the filesystem down to the tape layer. For the tape back-end it can be done by using Logical Block Protection, which computes and compares CRC checksum of every single block of data. During my work, I improved on-the-fly CRC calculation for the tape storage system, which was achieved by introducing a multithreaded implementation - a technique applicable to arbitrary CRC algorithm. Finally, I per...

QT/RR hysteresis as a function of RR excitation – implications for risk

Czech Academy of Sciences Publication Activity Database

Halámek, Josef; Jurák, Pavel; Somers, V. K.; Nykodým, J.; Leinveber, P.; Fráňa, P.; Eisenberger, M.; Kára, T.

2005-01-01

Roč. 4, č. 1 (2005), s. 98 [World Congress on Heart Disease - New Trends in Research, Diagnosis and Treatment /12./. 16.07.2005-19.07.2005, Vancouver] Institutional research plan: CEZ:AV0Z20650511 Keywords : ventricular repolarization * RR intervals Subject RIV: FA - Cardiovascular Disease s incl. Cardiotharic Surgery

More comprehensive discussion of CRC screening associated with higher screening.

Science.gov (United States)

Mosen, David M; Feldstein, Adrianne C; Perrin, Nancy A; Rosales, A Gabriella; Smith, David H; Liles, Elizabeth G; Schneider, Jennifer L; Meyers, Ronald E; Elston-Lafata, Jennifer

2013-04-01

Examine association of comprehensiveness of colorectal cancer (CRC) screening discussion by primary care physicians (PCPs) with completion of CRC screening. Observational study in Kaiser Permanente Northwest, a group-model health maintenance organization. A total of 883 participants overdue for CRC screening received an automated telephone call (ATC) between April and June 2009 encouraging CRC screening. Between January and March 2010, participants completed a survey on PCPs' discussion of CRC screening and patient beliefs regarding screening. receipt of CRC screening (assessed by electronic medical record [EMR], 9 months after ATC). Primary independent variable: comprehensiveness of CRC screening discussion by PCPs (7-item scale). Secondary independent variables: perceived benefits of screening (4-item scale assessing respondents' agreement with benefits of timely screening) and primary care utilization (EMR; 9 months after ATC). The independent association of variables with CRC screening was assessed with logistic regression. Average scores for comprehensiveness of CRC discussion and perceived benefits were 0.4 (range 0-1) and 4.0 (range 1-5), respectively. A total of 28.2% (n = 249) completed screening, 84% of whom had survey assessments after their screening date. Of screeners, 95.2% completed the fecal immunochemical test. More comprehensive discussion of CRC screening was associated with increased screening (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.03-2.21). Higher perceived benefits (OR = 1.46, 95% CI = 1.13-1.90) and 1 or more PCP visits (OR = 5.82, 95% CI = 3.87-8.74) were also associated with increased screening. More comprehensive discussion of CRC screening was independently associated with increased CRC screening. Primary care utilization was even more strongly associated with CRC screening, irrespective of discussion of CRC screening.

Fault isolation through no-overhead link level CRC

Science.gov (United States)

Chen, Dong; Coteus, Paul W.; Gara, Alan G.

2007-04-24

A fault isolation technique for checking the accuracy of data packets transmitted between nodes of a parallel processor. An independent crc is kept of all data sent from one processor to another, and received from one processor to another. At the end of each checkpoint, the crcs are compared. If they do not match, there was an error. The crcs may be cleared and restarted at each checkpoint. In the preferred embodiment, the basic functionality is to calculate a CRC of all packet data that has been successfully transmitted across a given link. This CRC is done on both ends of the link, thereby allowing an independent check on all data believed to have been correctly transmitted. Preferably, all links have this CRC coverage, and the CRC used in this link level check is different from that used in the packet transfer protocol. This independent check, if successfully passed, virtually eliminates the possibility that any data errors were missed during the previous transfer period.

Advances in CRC Prevention: Screening and Surveillance.

Science.gov (United States)

Dekker, Evelien; Rex, Douglas K

2018-05-01

Colorectal cancer (CRC) is among the most commonly diagnosed cancers and causes of death from cancer across the world. CRC can, however, be detected in asymptomatic patients at a curable stage, and several studies have shown lower mortality among patients who undergo screening compared with those who do not. Using colonoscopy in CRC screening also results in the detection of precancerous polyps that can be directly removed during the procedure, thereby reducing the incidence of cancer. In the past decade, convincing evidence has appeared that the effectiveness of colonoscopy as CRC prevention tool is associated with the quality of the procedure. This review aims to provide an up-to-date overview of recent efforts to improve colonoscopy effectiveness by enhancing detection and improving the completeness and safety of resection of colorectal lesions. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

High Rab27A expression indicates favorable prognosis in CRC.

Science.gov (United States)

Shi, Chuanbing; Yang, Xiaojun; Ni, Yijiang; Hou, Ning; Xu, Li; Zhan, Feng; Zhu, Huijun; Xiong, Lin; Chen, Pingsheng

2015-06-13

Rab27A is a peculiar member in Rab family and has been suggested to play essential roles in the development of human cancers. However, the association between Rab27A expression and clinicopathological characteristics of colorectal cancer (CRC) has not been elucidated yet. One-step quantitative real-time polymerase chain reaction (qPCR) test with 18 fresh-frozen CRC samples and immunohistochemistry (IHC) analysis in 112 CRC cases were executed to evaluate the relationship between Rab27A expression and the clinicopathological features of CRC. Cox regression and Kaplan-Meier survival analyses were performed to identify the prognostic factors for 112 CRC patients. The results specified that the expression levels of Rab27A mRNA and protein were significantly higher in CRC tissues than that in matched non-cancerous tissues, in both qPCR test (p = 0.029) and IHC analysis (p = 0.020). The IHC data indicated that the Rab27A protein expression in CRC was statistically correlated with lymph node metastasis (p = 0.022) and TNM stage (p = 0.026). Cox multi-factor analysis and Kaplan-Meier method suggested Rab27A protein expression (p = 0.012) and tumor differentiation (p = 0.004) were significantly associated with the overall survival of CRC patients. The data indicated the differentiate expression of Rab27A in CRC tissues and matched non-cancerous tissues. Rab27A may be used as a valuable prognostic biomarker for CRC patients.

The Half RR Rule: A Poor Rule of Thumb and Not a Risk Assessment Tool for QT Interval Prolongation.

Science.gov (United States)

Berling, Ingrid; Isbister, Geoffrey K

2015-10-01

Measuring the QT interval on an electrocardiogram (ECG) is integral to risk assessment of Torsade de Pointes (TdP). This study aimed to investigate the accuracy of the 1/2 RR rule as a risk assessment tool for drug-induced TdP, comparing it to the QT nomogram, Bazett's corrected QT (QTcB), and Fridericia's corrected QT (QTcF). The authors calculated sensitivity and specificity of the 1/2 RR rule using a published data set of 129 cases of drug-induced TdP and 316 controls (noncardiotoxic overdoses), compared to the QT nomogram, QTcB > 500 msec and QTcF > 500 msec. To further determine the value of the 1/2 RR rule, its observed positive, and negative agreement were calculated when compared to the QT nomogram for determining an abnormal QT in eight samples of different drugs in overdose. The sensitivity and specificity of the 1/2 RR rule were 88% (95% confidence interval [CI] = 80% to 93%) and 53% (95% CI = 47% to 58%), respectively, compared to the QT nomogram (sensitivity = 97%, 95% CI = 92% to 99%; specificity = 99%, 95% CI = 97% to 100%). It was also less sensitive than QTcB > 500 msec and had a lower specificity than QTcB > 500 msec and QTcF > 500 msec. In drug overdose patients, the 1/2 RR rule had poor observed agreement averaging 41%, which was mainly due to poor positive agreement, except for amisulpride where there was good agreement. The 1/2 RR rule was not as sensitive as the QT nomogram or QTcB > 500 msec for drug-induced TdP. It had poor positive agreement in almost all overdose patients, resulting in over half of patients receiving unnecessary cardiac monitoring and repeat ECGs. © 2015 by the Society for Academic Emergency Medicine.

Advances in CRC prevention: screening and surveillance

NARCIS (Netherlands)

Dekker, Evelien; Rex, Douglas K.

2018-01-01

Colorectal cancer (CRC) is amongst the most commonly diagnosed cancers and causes of death from cancer across the world. CRC can, however, be detected in asymptomatic patients at a curable stage, and several studies have shown lower mortality among patients who undergo screening compared to those

Mortality trends and risk of dying from colorectal cancer in the seven socioeconomic regions of Mexico, 2000-2012

Directory of Open Access Journals (Sweden)

J.J. Sánchez-Barriga

2017-07-01

Full Text Available Background: In Mexico, there has been an upward trend in mortality rates from colorectal cancer (CRC over the past three decades. This tumor is ranked among the ten most prevalent causes of morbidity from malignancies in Mexico. Aims: To determine the mortality trends by socioeconomic region and by state, and to establish the relative risk between both educational level and socioeconomic region with mortality from CRC within the time frame of 2000-2012. Materials and methods: Records of mortality associated with colorectal cancer were obtained. Rates of mortality by state and by socioeconomic region were calculated, along with the strength of association (obtained through the Poisson regression between both socioeconomic region and educational level and the mortality from CRC. Results: A total of 45,487 individuals died from CRC in Mexico from 2000 to 2012. Age-adjusted mortality rates per 100,000 inhabitants increased from 3.9 to 4.8. Baja California, Baja California Sur, and Sonora had the highest mortality from CRC. Individuals with no school or incomplete elementary school had a higher risk of dying from this cancer (RR of 3.57, 95% CI: 3.46-3.68. Region 7 had the strongest association with mortality from CRC (Mexico City: RR was 2.84, 95% CI: 2.39-3.37 [2000] and 3.32, 95% CI: 2.89-3.82 [2012]. Conclusions: In Mexico, the age-adjusted mortality rates per 100,000 inhabitants that died from CRC increased from 3.9 to 4.8 in the study period, using the world population age distribution as the standard. Baja California, Baja California Sur, and Sonora had the highest mortality from CRC. Mexico City, which was socioeconomic region 7, had the strongest association with mortality from CRC. Resumen: Introducción: En México ha habido una tendencia al alza en las tasas de mortalidad por cáncer colorrectal (CCR en las últimas 3 décadas. Esta neoplasia está clasificada dentro de las 10 causas más frecuentes de morbilidad por neoplasias malignas

System applications CRC -Biomass + Coal; Aplicaciones Sistema CRC-Biomasa+Carbon

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-07-01

Main object of Phase I of the project is to analyse the technical-economic feasibility of the combined use of biomass and coal for power generation in the Spanish region of Andalusia, by means of new medium-size independent power plants or using biomass as supplementary fuel in existing large coal power plants, including: -Analysis and classification of biomass and coal resources in the region -Technical-economic study of conventional alternatives using the steam cycle -Analysis of efficiency improvement provided by advanced Rankine-cycle technologies, like the SMR cycle -Analysis of alternatives based on parallel combined cycles using gas turbines, including advanced solutions, like the EAPI and CRC-EAPI systems. -Description and evaluation of different biomass drying systems. -Description and evaluation of the three main biomass gasification systems currently under development: atmospheric direct, atmospheric indirect and pressurized. Main objects of Phase II of the project are to analyse a specific application of the EAPI system to a real cogeneration plant project and to analyse the application of the CRC2 system to a commercial supercritical power plant, including technical-economic study of both applications. (Author)

Polar Coding with CRC-Aided List Decoding

Science.gov (United States)

2015-08-01

TECHNICAL REPORT 2087 August 2015 Polar Coding with CRC-Aided List Decoding David Wasserman Approved...list decoding . RESULTS Our simulation results show that polar coding can produce results very similar to the FEC used in the Digital Video...standard. RECOMMENDATIONS In any application for which the DVB-S2 FEC is considered, polar coding with CRC-aided list decod - ing with N = 65536

A Novel Least Significant Bit First Processing Parallel CRC Circuit

Directory of Open Access Journals (Sweden)

Xiujie Qu

2013-01-01

Full Text Available In HDLC serial communication protocol, CRC calculation can first process the most or least significant bit of data. Nowadays most CRC calculation is based on the most significant bit (MSB first processing. An algorithm of the least significant bit (LSB first processing parallel CRC is proposed in this paper. Based on the general expression of the least significant bit first processing serial CRC, using state equation method of linear system, we derive a recursive formula by the mathematical deduction. The recursive formula is applicable to any number of bits processed in parallel and any series of generator polynomial. According to the formula, we present the parallel circuit of CRC calculation and implement it with VHDL on FPGA. The results verify the accuracy and effectiveness of this method.

Expressions of IGF-1, ERK, GLUT4, IRS-1 in metabolic syndrome complicated with colorectal cancer and their associations with the clinical characteristics of CRC.

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Hu, Jianxia; Liu, Xiaoyi; Chi, Jingwei; Che, Kui; Feng, Yan; Zhao, Shihua; Wang, Zhongchao; Wang, Yangang

2018-01-01

Epidemiological data have revealed that colorectal cancer (CRC) risk is increased in patients with Metabolic syndrome. To explore the expressions of IGF-1, ERK, GLUT4, IRS-1 in MS patients with CRC and their associations with the clinical characteristics of CRC. We investigated the expressions of IGF-1, ERK, GLUT4 and IRS-1 in greater omental adipose tissues of 168 MS patients with/without CRC, 85 CRC patients without MS and 98 healthy controls by RT-PCR, and analyzed the relationships between their expressions and clinical characteristics of CRC. The expression levels of IGF-1 and ERK in MS patients with/without CRC were higher while the expression levels of GLUT4 were lower compared with CRC patients without MS and healthy controls (PCRC were higher while expression levels of GLUT4 were lower compared to MS patients without CRC (PCRC, including tumor size, distant metastasis and advanced stages (III/IV) (PCRC.

Age at menarche and risk of colorectal cancer: a meta-analysis.

Directory of Open Access Journals (Sweden)

Chun-Yan Li

Full Text Available BACKGROUND: Various observational studies have focused on the relationship between menarcheal age and the risk of colorectal cancer (CRC. However, the association is still controversial because of inconsistent results. Therefore, we performed a meta-analysis to assess this issue from epidemiological studies. METHODS: After a literature search in MEDLINE, EMBASE, and Web of Science for studies of menarcheal age and CRC risk published through the end of January 2013, we pooled the relative risks (RRs from included studies using a fixed- or random-effects model and performed heterogeneity and publication bias analyses. All statistical tests were two-sided. RESULTS: Eleven case-control and 11 cohort studies were eligible for inclusion in our analysis. The random-effects pooled RR for oldest versus youngest menarcheal age was 0.95 [95% confidence intervals (CIs = 0.85-1.06], with significant heterogeneity (Q = 61.03, P<0.001, I (2 = 65.6%. When separately analyzed, case-control (RR = 0.95, 95% CI = 0.75-1.21 and cohort studies (RR = 0.97, 95% CI = 0.90-1.04 yielded similar results. Moreover, similar results were also observed among the subgroup analyses by study quality, population, exposure assessment, anatomic cancer site, subsite of colon cancer, and several potential important confounders and risk factors. There was no evidence of publication bias and significant heterogeneity between subgroups detected by meta-regression analyses. CONCLUSIONS: Findings from this meta-analysis demonstrated that menarcheal age was not associated with the risk of CRC in humans. Further studies are warranted to stratify results by the subsite of colon cancer and menopause status in the future.

Spectral of electrocardiographic RR intervals to indicate atrial fibrillation

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Nuryani, Nuryani; Satrio Nugroho, Anto

2017-11-01

Atrial fibrillation is a serious heart diseases, which is associated on the risk of death, and thus an early detection of atrial fibrillation is necessary. We have investigated spectral pattern of electrocardiogram in relation to atrial fibrillation. The utilized feature of electrocardiogram is RR interval. RR interval is the time interval between a two-consecutive R peaks. A series of RR intervals in a time segment is converted to a signal with a frequency domain. The frequency components are investigated to find the components which significantly associate to atrial fibrillation. A segment is defined as atrial fibrillation or normal segments by considering a defined number of atrial fibrillation RR in the segment. Using clinical data of 23 patients with atrial fibrillation, we find that the frequency components could be used to indicate atrial fibrillation.

Disease severity does not affect the interval between IBD diagnosis and the development of CRC: results from two large, Dutch case series.

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Mooiweer, Erik; Baars, Judith E; Lutgens, Maurice W M D; Vleggaar, Frank; van Oijen, Martijn; Siersema, Peter D; Kuipers, Ernst J; van der Woude, C Janneke; Oldenburg, Bas

2012-05-01

The increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) is well established. The incidence of IBD-related CRC however, differs markedly between cohorts from referral centers and population-based studies. In the present study we aimed to identify characteristics potentially explaining these differences in two cohorts of patients with IBD-related CRC. PALGA, a nationwide pathology network and registry in The Netherlands, was used to search for patients with IBD-associated CRC between 1990 and 2006. Patients from 7 referral hospitals and 78 general hospitals were included. Demographic and disease specific parameters were collected retrospectively using patient charts. A total of 281 patients with IBD-associated CRC were identified. Patients from referral hospitals had a lower median age at IBD diagnosis (26 years vs. 28 years (p=0.02)), while having more IBD-relapses before CRC diagnosis than patients from general hospitals (3.8 vs. 1.5 (pCRC was diagnosed at a younger age (47 years vs. 51 years (p=0.01)). However, the median interval between IBD diagnosis and diagnosis of CRC was similar in both cohorts (19 years in referral hospitals vs. 17 years in general hospitals (p=0.13)). IBD patients diagnosed with CRC treated in referral hospitals in The Netherlands are younger at both the diagnosis of IBD and CRC than IBD patients with CRC treated in general hospitals. Although patients from referral centers appeared to have a more severe course of IBD, the interval between IBD and CRC diagnosis was similar. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

29 CFR 37.88 - Who may contact CRC about a complaint?

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2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Who may contact CRC about a complaint? 37.88 Section 37.88... PROVISIONS OF THE WORKFORCE INVESTMENT ACT OF 1998 (WIA) Compliance Procedures § 37.88 Who may contact CRC... contact CRC for information about the complaint. The Director will determine what information, if any...

Detection of colorectal cancer (CRC by urinary volatile organic compound analysis.

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Ramesh P Arasaradnam

Full Text Available Colorectal cancer (CRC is a leading cause of cancer related death in Europe and the USA. There is no universally accepted effective non-invasive screening test for CRC. Guaiac based faecal occult blood (gFOB testing has largely been superseded by Faecal Immunochemical testing (FIT, but sensitivity still remains poor. The uptake of population based FOBt testing in the UK is also low at around 50%. The detection of volatile organic compounds (VOCs signature(s for many cancer subtypes is receiving increasing interest using a variety of gas phase analytical instruments. One such example is FAIMS (Field Asymmetric Ion Mobility Spectrometer. FAIMS is able to identify Inflammatory Bowel disease (IBD patients by analysing shifts in VOCs patterns in both urine and faeces. This study extends this concept to determine whether CRC patients can be identified through non-invasive analysis of urine, using FAIMS. 133 patients were recruited; 83 CRC patients and 50 healthy controls. Urine was collected at the time of CRC diagnosis and headspace analysis undertaken using a FAIMS instrument (Owlstone, Lonestar, UK. Data was processed using Fisher Discriminant Analysis (FDA after feature extraction from the raw data. FAIMS analyses demonstrated that the VOC profiles of CRC patients were tightly clustered and could be distinguished from healthy controls. Sensitivity and specificity for CRC detection with FAIMS were 88% and 60% respectively. This study suggests that VOC signatures emanating from urine can be detected in patients with CRC using ion mobility spectroscopy technology (FAIMS with potential as a novel screening tool.

Detection of colorectal cancer (CRC) by urinary volatile organic compound analysis.

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Arasaradnam, Ramesh P; McFarlane, Michael J; Ryan-Fisher, Courtenay; Westenbrink, Erik; Hodges, Phoebe; Hodges, Paula; Thomas, Matthew G; Chambers, Samantha; O'Connell, Nicola; Bailey, Catherine; Harmston, Christopher; Nwokolo, Chuka U; Bardhan, Karna D; Covington, James A

2014-01-01

Colorectal cancer (CRC) is a leading cause of cancer related death in Europe and the USA. There is no universally accepted effective non-invasive screening test for CRC. Guaiac based faecal occult blood (gFOB) testing has largely been superseded by Faecal Immunochemical testing (FIT), but sensitivity still remains poor. The uptake of population based FOBt testing in the UK is also low at around 50%. The detection of volatile organic compounds (VOCs) signature(s) for many cancer subtypes is receiving increasing interest using a variety of gas phase analytical instruments. One such example is FAIMS (Field Asymmetric Ion Mobility Spectrometer). FAIMS is able to identify Inflammatory Bowel disease (IBD) patients by analysing shifts in VOCs patterns in both urine and faeces. This study extends this concept to determine whether CRC patients can be identified through non-invasive analysis of urine, using FAIMS. 133 patients were recruited; 83 CRC patients and 50 healthy controls. Urine was collected at the time of CRC diagnosis and headspace analysis undertaken using a FAIMS instrument (Owlstone, Lonestar, UK). Data was processed using Fisher Discriminant Analysis (FDA) after feature extraction from the raw data. FAIMS analyses demonstrated that the VOC profiles of CRC patients were tightly clustered and could be distinguished from healthy controls. Sensitivity and specificity for CRC detection with FAIMS were 88% and 60% respectively. This study suggests that VOC signatures emanating from urine can be detected in patients with CRC using ion mobility spectroscopy technology (FAIMS) with potential as a novel screening tool.

CRC concise encyclopedia of mathematics

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Weisstein, Eric W

2003-01-01

Upon publication, the first edition of the CRC Concise Encyclopedia of Mathematics received overwhelming accolades for its unparalleled scope, readability, and utility. It soon took its place among the top selling books in the history of Chapman & Hall/CRC, and its popularity continues unabated. Yet also unabated has been the dedication of author Eric Weisstein to collecting, cataloging, and referencing mathematical facts, formulas, and definitions. He has now updated most of the original entries and expanded the Encyclopedia to include 1000 additional pages of illustrated entries. The accessibility of the Encyclopedia along with its broad coverage and economical price make it attractive to the widest possible range of readers and certainly a must for libraries, from the secondary to the professional and research levels. For mathematical definitions, formulas, figures, tabulations, and references, this is simply the most impressive compendium available.

Performance Analysis of CRC Codes for Systematic and Nonsystematic Polar Codes with List Decoding

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Takumi Murata

2018-01-01

Full Text Available Successive cancellation list (SCL decoding of polar codes is an effective approach that can significantly outperform the original successive cancellation (SC decoding, provided that proper cyclic redundancy-check (CRC codes are employed at the stage of candidate selection. Previous studies on CRC-assisted polar codes mostly focus on improvement of the decoding algorithms as well as their implementation, and little attention has been paid to the CRC code structure itself. For the CRC-concatenated polar codes with CRC code as their outer code, the use of longer CRC code leads to reduction of information rate, whereas the use of shorter CRC code may reduce the error detection probability, thus degrading the frame error rate (FER performance. Therefore, CRC codes of proper length should be employed in order to optimize the FER performance for a given signal-to-noise ratio (SNR per information bit. In this paper, we investigate the effect of CRC codes on the FER performance of polar codes with list decoding in terms of the CRC code length as well as its generator polynomials. Both the original nonsystematic and systematic polar codes are considered, and we also demonstrate that different behaviors of CRC codes should be observed depending on whether the inner polar code is systematic or not.

12 CFR 617.7310 - What is the review process of the CRC?

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2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false What is the review process of the CRC? 617.7310... on Applications; Review of Credit Decisions § 617.7310 What is the review process of the CRC? (a) How will an applicant or borrower know when the CRC will consider the review request? The qualified lender...

The Pseudomonas aeruginosa catabolite repression control protein Crc is devoid of RNA binding activity.

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Milojevic, Tetyana; Grishkovskaya, Irina; Sonnleitner, Elisabeth; Djinovic-Carugo, Kristina; Bläsi, Udo

2013-01-01

The Crc protein has been shown to mediate catabolite repression control in Pseudomonas, leading to a preferential assimilation of carbon sources. It has been suggested that Crc acts as a translational repressor of mRNAs, encoding functions involved in uptake and breakdown of different carbon sources. Moreover, the regulatory RNA CrcZ, the level of which is increased in the presence of less preferred carbon sources, was suggested to bind to and sequester Crc, resulting in a relief of catabolite repression. Here, we determined the crystal structure of Pseudomonas aeruginosa Crc, a member of apurinic/apyrimidinic (AP) endonuclease family, at 1.8 Å. Although Crc displays high sequence similarity with its orthologs, there are amino acid alterations in the area corresponding to the active site in AP proteins. Unlike typical AP endonuclease family proteins, Crc has a reduced overall positive charge and the conserved positively charged amino-acid residues of the DNA-binding surface of AP proteins are partially substituted by negatively charged, polar and hydrophobic residues. Crc protein purified to homogeneity from P. aeruginosa did neither display DNase activity, nor did it bind to previously identified RNA substrates. Rather, the RNA chaperone Hfq was identified as a contaminant in His-tagged Crc preparations purified by one step Ni-affinity chromatography from Escherichia coli, and was shown to account for the RNA binding activity observed with the His-Crc preparations. Taken together, these data challenge a role of Crc as a direct translational repressor in carbon catabolite repression in P. aeruginosa.

Structure analysis of the global metabolic regulator Crc from Pseudomonas aeruginosa.

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Wei, Yong; Zhang, Heng; Gao, Zeng-Qiang; Xu, Jian-Hua; Liu, Quan-Sheng; Dong, Yu-Hui

2013-01-01

The global metabolic regulator catabolite repression control (Crc) has recently been found to modulate the susceptibility to antibiotics and virulence in the opportunistic pathogen Pseudomonas aeruginosa and been suggested as a nonlethal target for novel antimicrobials. In P. aeruginosa, Crc couples with the CA motifs from the small RNA CrcZ to form a post-transcriptional regulator system and is removed from the 5'-end of the target mRNAs. In this study, we first reported the crystal structure of Crc from P. aeruginosa refined to 2.20 Å. The structure showed that it consists of two halves with similar overall topology and there are 11 β strands surrounded by 13 helices, forming a four-layered α/β-sandwich. The circular dichroism spectroscopy revealed that it is thermostable in solution and shares similar characteristics to that in crystal. Comprehensive structural analysis and comparison with the homologies of Crc showed high similarity with several known nucleases and consequently may be classified into a member exodeoxyribonuclease III. However, it shows distinct substrate specificity (RNA as the preferred substrate) compared to these DNA endonucleases. Structural comparisons also revealed potential RNA recognition and binding region mainly consisting of five flexible loops. Our structure study provided the basis for the future application of Crc as a target to develop new antibiotics. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

CRC-cards to support development and maintenance of product configuration systems

DEFF Research Database (Denmark)

Haug, Anders; Hvam, Lars

2009-01-01

This article presents a new definition of special Class, Responsibility and Collaboration (CRC) cards to be used for the development and maintenance of Product Configuration Systems (PCSs). CRC cards were introduced as an informal and user-friendly technique for teaching object-oriented modelling...... and maintenance of PCSs. This procedure has since been applied in several configuration projects and further developed at the Centre for Product Modelling (CPM) at the Technical University of Denmark. However, the investigations of two companies that applies CRC cards to document the knowledge base of their PCSs...

The Preoperative Peripheral Blood Monocyte Count Is Associated with Liver Metastasis and Overall Survival in Colorectal Cancer Patients.

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Shidong Hu

Full Text Available Colorectal cancer (CRC is the third most common malignancy in males and the second most common in females worldwide. Distant metastases have a strong negative impact on the prognosis of CRC patients. The most common site of CRC metastases is the liver. Both disease progression and metastasis have been related to the patient's peripheral blood monocyte count. We therefore performed a case-control study to assess the relationship between the preoperative peripheral blood monocyte count and colorectal liver metastases (CRLM.Clinical data from 117 patients with colon cancer and 93 with rectal cancer who were admitted to the Chinese People's Liberation Army General Hospital (Beijing, China between December 2003 and May 2015 were analysed retrospectively, with the permission of both the patients and the hospital.Preoperative peripheral blood monocyte counts, the T and N classifications of the primary tumour and its primary site differed significantly between the two groups (P 0.505 × 109 cells/L, high T classification and liver metastasis were independent risk factors for 5-year OS (RR: 2.737, 95% CI: 1.573~ 4.764, P <0.001; RR: 2.687, 95%CI: 1.498~4.820, P = 0.001; RR: 4.928, 95%CI: 2.871~8.457, P < 0.001.The demonstrated association between preoperative peripheral blood monocyte count and liver metastasis in patients with CRC recommends the former as a useful predictor of postoperative prognosis in CRC patients.

The Preoperative Peripheral Blood Monocyte Count Is Associated with Liver Metastasis and Overall Survival in Colorectal Cancer Patients.

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Hu, Shidong; Zou, Zhenyu; Li, Hao; Zou, Guijun; Li, Zhao; Xu, Jian; Wang, Lingde; Du, Xiaohui

2016-01-01

Colorectal cancer (CRC) is the third most common malignancy in males and the second most common in females worldwide. Distant metastases have a strong negative impact on the prognosis of CRC patients. The most common site of CRC metastases is the liver. Both disease progression and metastasis have been related to the patient's peripheral blood monocyte count. We therefore performed a case-control study to assess the relationship between the preoperative peripheral blood monocyte count and colorectal liver metastases (CRLM). Clinical data from 117 patients with colon cancer and 93 with rectal cancer who were admitted to the Chinese People's Liberation Army General Hospital (Beijing, China) between December 2003 and May 2015 were analysed retrospectively, with the permission of both the patients and the hospital. Preoperative peripheral blood monocyte counts, the T and N classifications of the primary tumour and its primary site differed significantly between the two groups (P colon cancer (OR: 0.078, 95%CI: 0.020~0.309, P 0.505 × 109 cells/L, high T classification and liver metastasis were independent risk factors for 5-year OS (RR: 2.737, 95% CI: 1.573~ 4.764, P <0.001; RR: 2.687, 95%CI: 1.498~4.820, P = 0.001; RR: 4.928, 95%CI: 2.871~8.457, P < 0.001). The demonstrated association between preoperative peripheral blood monocyte count and liver metastasis in patients with CRC recommends the former as a useful predictor of postoperative prognosis in CRC patients.

Cross-regulation by CrcZ RNA controls anoxic biofilm formation in Pseudomonas aeruginosa

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Pusic, Petra; Tata, Muralidhar; Wolfinger, Michael T.; Sonnleitner, Elisabeth; Häussler, Susanne; Bläsi, Udo

2016-12-01

Pseudomonas aeruginosa (PA) can thrive in anaerobic biofilms in the lungs of cystic fibrosis (CF) patients. Here, we show that CrcZ is the most abundant PA14 RNA bound to the global regulator Hfq in anoxic biofilms grown in cystic fibrosis sputum medium. Hfq was crucial for anoxic biofilm formation. This observation complied with an RNAseq based transcriptome analysis and follow up studies that implicated Hfq in regulation of a central step preceding denitrification. CrcZ is known to act as a decoy that sequesters Hfq during relief of carbon catabolite repression, which in turn alleviates Hfq-mediated translational repression of catabolic genes. We therefore inferred that CrcZ indirectly impacts on biofilm formation by competing for Hfq. This hypothesis was supported by the findings that over-production of CrcZ mirrored the biofilm phenotype of the hfq deletion mutant, and that deletion of the crcZ gene augmented biofilm formation. To our knowledge, this is the first example where competition for Hfq by CrcZ cross-regulates an Hfq-dependent physiological process unrelated to carbon metabolism.

The CRC orthologue from Pisum sativum shows conserved functions in carpel morphogenesis and vascular development.

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Fourquin, Chloé; Primo, Amparo; Martínez-Fernández, Irene; Huet-Trujillo, Estefanía; Ferrándiz, Cristina

2014-11-01

CRABS CLAW (CRC) is a member of the YABBY family of transcription factors involved in carpel morphogenesis, floral determinacy and nectary specification in arabidopsis. CRC orthologues have been functionally characterized across angiosperms, revealing additional roles in leaf vascular development and carpel identity specification in Poaceae. These studies support an ancestral role of CRC orthologues in carpel development, while roles in vascular development and nectary specification appear to be derived. This study aimed to expand research on CRC functional conservation to the legume family in order to better understand the evolutionary history of CRC orthologues in angiosperms. CRC orthologues from Pisum sativum and Medicago truncatula were identified. RNA in situ hybridization experiments determined the corresponding expression patterns throughout flower development. The phenotypic effects of reduced CRC activity were investigated in P. sativum using virus-induced gene silencing. CRC orthologues from P. sativum and M. truncatula showed similar expression patterns, mainly restricted to carpels and nectaries. However, these expression patterns differed from those of other core eudicots, most importantly in a lack of abaxial expression in the carpel and in atypical expression associated with the medial vein of the ovary. CRC downregulation in pea caused defects in carpel fusion and style/stigma development, both typically associated with CRC function in eudicots, but also affected vascular development in the carpel. The data support the conserved roles of CRC orthologues in carpel fusion, style/stigma development and nectary development. In addition, an intriguing new aspect of CRC function in legumes was the unexpected role in vascular development, which could be shared by other species from widely diverged clades within the angiosperms, suggesting that this role could be ancestral rather than derived, as so far generally accepted. © The Author 2014. Published by

Observations on Polar Coding with CRC-Aided List Decoding

Science.gov (United States)

2016-09-01

TECHNICAL REPORT 3041 September 2016 Observations on Polar Coding with CRC-Aided List Decoding David Wasserman Approved for public release. SSC...described in [2, 3]. In FY15 and FY16 we used cyclic redundancy check (CRC)-aided polar list decoding [4]. Section 2 describes the basics of polar coding ...and gives details of the encoders and decoders we used. In the course of our research, we performed simulations of polar codes in hundreds of cases

12 CFR 617.7305 - What is a CRC and who are the members?

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2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false What is a CRC and who are the members? 617.7305... on Applications; Review of Credit Decisions § 617.7305 What is a CRC and who are the members? The... decisions made by a qualified lender. The CRC may only review adverse credit decisions at the request of the...

How does the serrated polyp pathway alter CRC screening and surveillance?

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Kahi, Charles J

2015-03-01

Screening and surveillance for colorectal cancer (CRC) reduces mortality through the detection of early-stage adenocarcinoma, and more importantly the detection and removal of premalignant polyps. While adenomas have historically been considered the most common and screening-relevant precursor lesions, there is accumulating evidence showing that the serrated pathway is an important contributor to CRC, and a disproportionate contributor to interval or postcolonoscopy CRC, particularly in the proximal colon. The serrated pathway is characterized by mutations in the BRAF gene, high levels of methylation of promoter CpG islands (CIMP-high), and the sessile serrated adenoma/polyp (SSA/P) is the most important precursor lesion. The study of serrated polyps has been complicated by evolving nomenclature, substantial variation among pathologists in the identification of SSA/Ps, high variability in endoscopic detection rates, and uncertainty regarding the relation to synchronous and metachronous colonic neoplasia. This paper presents an overview of the serrated polyp pathway and discusses its clinical implications including its impact on CRC screening.

An examination of the psychosocial factors influencing colorectal cancer patients' communication of colorectal cancer patient risk with their siblings.

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Lawsin, Catalina; Duhamel, Katherine; Itzkowitz, Steven; Brown, Karen; Lim, Helen; Jandorf, Lina

2009-11-01

This study examined psychosocial factors influencing colorectal cancer (CRC) patients' communication with their first-degree relatives regarding their CRC risk. Among a sample of CRC patients who were members of a colon registry in New York (n = 127), 60% reported discussing CRC risk with their siblings. These discussions were related to the CRC patients' age of diagnosis, such that those diagnosed before age 45 years were more likely to communicate with their siblings about CRC risk. Despite advances made in CRC prevention, compliance with screening recommendations among individuals who may be at familial risk for the disease is low. Perhaps this underrepresentation reflects how CRC patients communicate with their first-degree relatives about their potential risk for the disease. This study examined the psychosocial factors influencing whether CRC patients communicate with their siblings about CRC risk. The sample included CRC patients with siblings who enrolled in a colon disease registry at a NYC metropolitan hospital. Participants completed questionnaires regarding their current psychosocial functioning, perceived risk of sibling's development of CRC, and communication of CRC risk with their siblings. Patients were predominantly Caucasian, with a mean age of 60.4 years. Of the 127 patients, 60% engaged in discussions with their siblings regarding their CRC risk. Patients diagnosed with CRC before the age of 45 years were more likely to discuss the risk of CRC with their siblings (P siblings.

29 CFR 37.38 - What information must grant applicants and recipients provide to CRC?

Science.gov (United States)

2010-07-01

... provide to CRC? 37.38 Section 37.38 Labor Office of the Secretary of Labor IMPLEMENTATION OF THE... information must grant applicants and recipients provide to CRC? In addition to the information which must be collected, maintained, and, upon request, submitted to CRC under § 37.37: (a) Each grant applicant and...

Potential role of TRIM3 as a novel tumour suppressor in colorectal cancer (CRC) development.

Science.gov (United States)

Piao, Mei-Yu; Cao, Hai-Long; He, Na-Na; Xu, Meng-Que; Dong, Wen-Xiao; Wang, Wei-Qiang; Wang, Bang-Mao; Zhou, Bing

2016-01-01

Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the United States. Recent cancer genome-sequencing efforts and complementary functional studies have led to the identification of a collection of candidate 'driver' genes involved in CRC tumorigenesis. Tripartite motif (TRIM3) is recently identified as a tumour suppressor in glioblastoma but this tumour-suppressive function has not been investigated in CRC. In this study, we investigated the potential role of TRIM3 as a tumour suppressor in CRC development by manipulating the expression of TRIM3 in two authentic CRC cell lines, HCT116 and DLD1, followed by various functional assays, including cell proliferation, colony formation, scratch wound healing, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumour-suppressive properties of TRIM3. Small-interfering RNA (siRNA) mediated knockdown of TRIM3 conferred growth advantage in CRC cells. In contrast, overexpression of TRIM3 affected cell survival, cell migration, anchorage independent growth and invasive potential in CRC cells. In addition, TRIM3 was found to be down-regulated in human colon cancer tissues compared with matched normal colon tissues. Overexpression of TRIM3 significantly inhibited tumour growth in vivo using xenograft mouse models. Mechanistic investigation revealed that TRIM3 can regulate p53 protein level through its stabilisation. TRIM3 functions as a tumour suppressor in CRC progression. This tumour-suppressive function is exerted partially through regulation of p53 protein. Therefore, this protein may represent a novel therapeutic target for prevention or intervention of CRC.

Pickled meat consumption and colorectal cancer (CRC): a case-control study in Newfoundland and Labrador, Canada.

Science.gov (United States)

Squires, Josh; Roebothan, Barbara; Buehler, Sharon; Sun, Zhuoyu; Cotterchio, Michelle; Younghusband, Ban; Dicks, Elizabeth; Mclaughlin, John R; Parfrey, Patrick S; Wang, Peizhong Peter

2010-09-01

Although a large body of epidemiological research suggests that red meat intake increases the risk of colorectal cancer, little is known regarding how such an association varies across populations and types of red meat. The objective of this study was to assess whether an association exists between the intakes of total red meat and pickled red meat and the risk of colorectal cancer in study subjects residing in Newfoundland and Labrador. This case-control study of 1,204 residents of Newfoundland and Labrador was part of a larger study on colorectal cancer. Personal history food frequency questionnaires were used to collect retrospective data from 518 individuals diagnosed with colorectal cancer and 686 controls. Intakes were ranked and divided into tertiles. Logistic regression was used to examine the possible association between meat intakes and colorectal cancer diagnosis while controlling for possible confounding factors. A positive, but non-statistically significant, association between total red meat intake and CRC was observed in this study. Pickled red meat consumption was found to be significantly associated with an increased risk of CRC (men, OR = 2.07, 95% CI 1.37-3.15; women, OR = 2.51, 95% CI 1.45-4.32), the odds ratios increasing with each tertile of consumption, suggesting a dose-response effect. Intake of pickled red meat appears to increase the risk of colorectal cancer in Newfoundland and Labrador.

Dietary Inflammatory Index and Colorectal Cancer Risk—A Meta-Analysis

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Nitin Shivappa

2017-09-01

Full Text Available Diet and chronic inflammation of the colon have been suggested to be risk factors in the development of colorectal cancer (CRC. The possible link between inflammatory potential of diet, measured through the Dietary Inflammatory Index (DII®, and CRC has been investigated in several populations across the world. The aim of this study was to conduct a meta-analysis on studies exploring this association. Data from nine studies were eligible, of which five were case-control and four were cohort studies. Results from meta-analysis showed a positive association between increasing DII scores, indicating a pro-inflammatory diet, and CRC. Individuals in the highest versus the lowest (reference DII category showed an overall 40% increased risk of CRC with moderate evidence of heterogeneity [relative risk (RR = 1.40, 95% confidence interval (CI: 1.26, 1.55; I2 = 69%, p < 0.001]. When analyzed as a continuous variable, results showed an increased risk of CRC of 7% for a 1-point increase in the DII score. Results remained unchanged when analyses were restricted to the four prospective studies. Results of our meta-analysis support the importance of adopting a healthier anti-inflammatory diet in preventing CRC. These results further substantiate the utility of DII as tool to characterize the inflammatory potential of diet and to predict CRC.

Probiotics in colorectal cancer (CRC) with emphasis on mechanisms of action and current perspectives.

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Kahouli, Imen; Tomaro-Duchesneau, Catherine; Prakash, Satya

2013-08-01

Colorectal cancer (CRC) is the third most common form of cancer. Diverse therapies such as chemotherapy, immunotherapy and radiation have shown beneficial effects, but are limited because of their safety and toxicity. Probiotic formulations have shown great promise in CRC as preventive and early stage therapeutics. This review highlights the importance of a balanced intestinal microbiota and summarizes the recent developments in probiotics for treating CRC. Specifically, this report describes evidence of the role of probiotics in modulating the microbiota, in improving the physico-chemical conditions of the gut and in reducing oxidative stress. It also discusses the mechanisms of probiotics in inhibiting tumour progression, in producing anticancer compounds and in modulating the host immune response. Even though some of these effects were observed in several clinical trials, when probiotic formulations were used as a supplement to CRC therapies, the application of probiotics as biotherapeutics against CRC still needs further investigation.

ZEB1 Mediates Drug Resistance and EMT in p300-Deficient CRC.

Science.gov (United States)

Lazarova, Darina; Bordonaro, Michael

2017-01-01

We discuss the hypothesis that ZEB1-Wnt-p300 signaling integrates epithelial to mesenchymal transition (EMT) and resistance to histone deacetylase inhibitors (HDACis) in colorectal cancer (CRC) cells. The HDACi butyrate, derived from dietary fiber, has been linked to CRC prevention, and other HDACis have been proposed as therapeutic agents against CRC. We have previously discussed that resistance to butyrate likely contributes to colonic carcinogenesis, and we have demonstrated that butyrate resistance leads to cross-resistance to cancer therapeutic HDACis. Deregulated Wnt signaling is the major initiating event in most CRC cases. One mechanism whereby butyrate and other HDACis exert their anti-CRC effects is via Wnt signaling hyperactivation, which promotes CRC cell apoptosis. The histone acetylases (HATs) CBP and p300 are mediators of Wnt transcriptional activity, and play divergent roles in the downstream consequences of Wnt signaling. CBP-mediated Wnt signaling is associated with cell proliferation and stem cell maintenance; whereas, p300-mediated Wnt activity is associated with differentiation. We have found that CBP and p300 differentially affect the ability of butyrate to influence Wnt signaling, apoptosis, and proliferation. ZEB 1 is a Wnt signaling-targeted gene, whose product is a transcription factor expressed at the invasive front of carcinomas where it promotes malignant progression and EMT. ZEB1 is typically a transcriptional repressor; however, when associated with p300, ZEB1 enhances transcription. These changes in ZEB1 activity likely affect the cancer cell phenotype. ZEB1 has been shown to promote resistance to chemotherapeutic agents, and expression of ZEB1 is upregulated in butyrate-resistant CRC cells that lack p300 expression. Since the expression of ZEB1 correlates with poor outcomes in cancer, ZEB represents a relevant therapeutic target. Here we propose that targeting the signaling network established by ZEB1, Wnt signaling, and p300

Neighborhood disadvantage and racial disparities in colorectal cancer incidence: a population-based study in Louisiana.

Science.gov (United States)

Danos, Denise M; Ferguson, Tekeda F; Simonsen, Neal R; Leonardi, Claudia; Yu, Qingzhao; Wu, Xiao-Cheng; Scribner, Richard A

2018-05-01

Colorectal cancer (CRC) continues to demonstrate racial disparities in incidence and survival in the United States. This study investigates the role of neighborhood concentrated disadvantage in racial disparities in CRC incidence in Louisiana. Louisiana Tumor Registry and U.S. Census data were used to assess the incidence of CRC diagnosed in individuals 35 years and older between 2008 and 2012. Neighborhood concentrated disadvantage index (CDI) was calculated based on the PhenX Toolkit protocol. The incidence of CRC was modeled using multilevel binomial regression with individuals nested within neighborhoods. Our study included 10,198 cases of CRC. Adjusting for age and sex, CRC risk was 28% higher for blacks than whites (risk ratio [RR] = 1.28; 95% confidence interval [CI] = 1.22-1.33). One SD increase in CDI was associated with 14% increase in risk for whites (RR = 1.14; 95% CI = 1.10-1.18) and 5% increase for blacks (RR = 1.05; 95% CI = 1.02-1.09). After controlling for differential effects of CDI by race, racial disparities were not observed in disadvantaged areas. CRC incidence increased with neighborhood disadvantage and racial disparities diminished with mounting disadvantage. Our results suggest additional dimensions to racial disparities in CRC outside of neighborhood disadvantage that warrants further research. Copyright © 2018 Elsevier Inc. All rights reserved.

MiR-608, pre-miR-124-1 and pre-miR26a-1 polymorphisms modify susceptibility and recurrence-free survival in surgically resected CRC individuals.

Science.gov (United States)

Ying, Hou-Qun; Peng, Hong-Xin; He, Bang-Shun; Pan, Yu-Qin; Wang, Feng; Sun, Hui-Ling; Liu, Xian; Chen, Jie; Lin, Kang; Wang, Shu-Kui

2016-11-15

Genetic variation within microRNA (miRNA) may result in its abnormal folding or aberrant expression, contributing to colorectal turmorigenesis and metastasis. However, the association of six polymorphisms (miR-608 rs4919510, miR-499a rs3746444, miR-146a rs2910164, pre-miR-143 rs41291957, pre-miR-124-1 rs531564 and pre-miR-26a-1 rs7372209) with colorectal cancer (CRC) risk, therapeutic response and survival remains unclear. A retrospective study was carried out to investigate the association in 1358 0-III stage resected CRC patients and 1079 healthy controls using Sequenom's MassARRAY platform. The results showed that rs4919510 was significantly associated with a decreased susceptibility to CRC in co-dominant, allele and recessive genetic models, and the protective role of rs4919510 allele G and genotype GG was more pronounced among stage 0-II cases; significant association between rs531564 and poor RFS was observed in cases undergoing adjuvant chemo-radiotherapy in co-dominant, allele and dominant models; moreover, there was a positive association between rs7372209 and recurrence-free survival in stage II cases in co-dominant and over-dominant models; additionally, a cumulative effect of rs531564 and rs7372209 at-risk genotypes with hazard ratio at 1.30 and 1.95 for one and two at-risk genotypes was examined in stage II cases, respectively. Our findings indicated that rs4919510 allele G and genotype GG were protective factors for 0-II stage CRC, rs7372209 and rs531564 could decrease RFS in II stage individuals and resected CRC patients receiving adjuvant chemo-radiology.

Long noncoding RNA lnc-sox5 modulates CRC tumorigenesis by unbalancing tumor microenvironment.

Science.gov (United States)

Wu, Kaiming; Zhao, Zhenxian; Liu, Kuanzhi; Zhang, Jian; Li, Guanghua; Wang, Liang

2017-07-03

Long non-coding RNAs (LncRNAs) have been recently regarded as systemic regulators in multiple biologic processes including tumorigenesis. In this study, we observed the expression of lncRNA lnc-sox5 was significantly increased in colorectal cancer (CRC). Despite the CRC cell growth, cell cycle and cell apoptosis was not affected by lnc-sox5 knock-down, lnc-sox5 knock-down suppressed CRC cell migration and invasion. In addition, xenograft animal model suggested that lnc-sox5 knock-down significantly suppressed the CRC tumorigenesis. Our results also showed that the expression of indoleamine 2,3-dioxygenase 1 (IDO1) was significantly reduced by lnc-sox5 knock-down and therefore modulated the infiltration and cytotoxicity of CD3 + CD8 + T cells. Taken together, these results suggested that lnc-sox5 unbalances tumor microenvironment to regulate colorectal cancer progression.

29 CFR 37.84 - What happens if CRC does not have jurisdiction over a complaint?

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true What happens if CRC does not have jurisdiction over a complaint? 37.84 Section 37.84 Labor Office of the Secretary of Labor IMPLEMENTATION OF THE... Procedures § 37.84 What happens if CRC does not have jurisdiction over a complaint? If CRC does not have...

Association between hMLH1 hypermethylation and JC virus (JCV) infection in human colorectal cancer (CRC).

Science.gov (United States)

Vilkin, Alex; Niv, Yaron

2011-04-01

Incorporation of viral DNA may interfere with the normal sequence of human DNA bases on the genetic level or cause secondary epigenetic changes such as gene promoter methylation or histone acetylation. Colorectal cancer (CRC) is the second leading cause of cancer mortality in the USA. Chromosomal instability (CIN) was established as the key mechanism in cancer development. Later, it was found that CRC results not only from the progressive accumulation of genetic alterations but also from epigenetic changes. JC virus (JCV) is a candidate etiologic factor in sporadic CRC. It may act by stabilizing β-catenin, facilitating its entrance to the cell nucleus, initialing proliferation and cancer development. Diploid CRC cell lines transfected with JCV-containing plasmids developed CIN. This result provides direct experimental evidence for the ability of JCV T-Ag to induce CIN in the genome of colonic epithelial cells. The association of CRC hMLH1 methylation and tumor positivity for JCV was recently documented. JC virus T-Ag DNA sequences were found in 77% of CRCs and are associated with promoter methylation of multiple genes. hMLH1 was methylated in 25 out of 80 CRC patients positive for T-Ag (31%) in comparison with only one out of 11 T-Ag negative cases (9%). Thus, JCV can mediate both CIN and aberrant methylation in CRC. Like other viruses, chronic infection with JCV may induce CRC by different mechanisms which should be further investigated. Thus, gene promoter methylation induced by JCV may be an important process in CRC and the polyp-carcinoma sequence.

RGC32 induces epithelial-mesenchymal transition by activating the Smad/Sip1 signaling pathway in CRC.

Science.gov (United States)

Wang, Xiao-Yan; Li, Sheng-Nan; Zhu, Hui-Fang; Hu, Zhi-Yan; Zhong, Yan; Gu, Chuan-Sha; Chen, Shi-You; Liu, Teng-Fei; Li, Zu-Guo

2017-05-04

Response gene to complement 32 (RGC32) is a transcription factor that regulates the expression of multiple genes involved in cell growth, viability and tissue-specific differentiation. However, the role of RGC32 in tumorigenesis and tumor progression in colorectal cancer (CRC) has not been fully elucidated. Here, we showed that the expression of RGC32 was significantly up-regulated in human CRC tissues versus adjacent normal tissues. RGC32 expression was significantly correlated with invasive and aggressive characteristics of tumor cells, as well as poor survival of CRC patients. We also demonstrated that RGC32 overexpression promoted proliferation, migration and tumorigenic growth of human CRC cells in vitro and in vivo. Functionally, RGC32 facilitated epithelial-mesenchymal transition (EMT) in CRC via the Smad/Sip1 signaling pathway, as shown by decreasing E-cadherin expression and increasing vimentin expression. In conclusion, our findings suggested that overexpression of RGC32 facilitates EMT of CRC cells by activating Smad/Sip1 signaling.

Anatomic Subsite of Primary Colorectal Cancer and Subsequent Risk and Distribution of Second Cancers

Science.gov (United States)

Phipps, Amanda I.; Chan, Andrew T.; Shuji Ogino, MD

2013-01-01

Background Individuals with a history of colorectal cancer (CRC) have an increased risk of subsequent cancer. We used cancer registry data to evaluate whether this increased risk of cancer after CRC differed by anatomic subsite of a first CRC. Methods Individuals diagnosed with first primary CRC between 1992–2009 were identified from 12 Surveillance Epidemiology and End Results (SEER) cancer registries. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) comparing the incidence of subsequent cancers in these index CRC cases to cancer incidence rates in the general population. SIRs were calculated for cancers at anatomic sites within and outside the colorectum in analyses stratified by subsite of the index CRC. Results Cancer incidence rates were significantly higher in those with prior CRC than in the general population (SIR=1.15, 95% CI: 1.13–1.16). Individuals with an index CRC located between the transverse and descending colon experienced the greatest increased risk both overall (SIR=1.29 to 1.33), and with respect to risk of second CRC in particular (SIR=2.53 to 3.35). Incidence of small intestinal cancer was significantly elevated regardless of index CRC subsite (SIR=4.31, 95% CI: 3.70–4.77); incidence of endometrial cancer was elevated in those with index CRC in the proximal colon (SIR=1.37 to 1.79). Conclusions Risk of second cancer after CRC differs by anatomic site of the first tumor, and is particularly pronounced for those with prior CRC located in the transverse to descending colon. The mechanisms underlying this pattern of second cancer risk remain unknown. PMID:23856984

12 CFR 617.7315 - What records must the qualified lender maintain on behalf of the CRC?

Science.gov (United States)

2010-01-01

... on behalf of the CRC? 617.7315 Section 617.7315 Banks and Banking FARM CREDIT ADMINISTRATION FARM... must the qualified lender maintain on behalf of the CRC? A qualified lender must maintain a complete file of all requests for CRC reviews, including participation in state mediation programs, the minutes...

Risk Management and Simulation

DEFF Research Database (Denmark)

Skovmand, David

2014-01-01

Review of: Risk Management and Simulation / Aparna Gupta. Boca Raton, FL: CRC Press, 2013, xxix + 491 pp., $99.95(H), ISBN: 978-1-4398-3594-4.......Review of: Risk Management and Simulation / Aparna Gupta. Boca Raton, FL: CRC Press, 2013, xxix + 491 pp., $99.95(H), ISBN: 978-1-4398-3594-4....

Report: Cultural Research Centre (CRC)

OpenAIRE

Cross-Cultural Foundation of Uganda

2010-01-01

This report arises from research carried out in Iganga and Namutumba districts in late 2006/early 2007 by the Cultural Research Centre (CRC), based in Jinja. Our research focus was to gauge the impact of using Lusoga as a medium of instruction (since 2005 in "pilot" lower primary classes) within and outside the classroom. This initiative was in response to a new set of circumstances in the education sector in Uganda, especially the introduction by Government of teaching in local languages in ...

Dairy product consumption and risk of colorectal cancer in an older mediterranean population at high cardiovascular risk.

Science.gov (United States)

Barrubés, Laura; Babio, Nancy; Mena-Sánchez, Guillermo; Toledo, Estefania; Ramírez-Sabio, Judith B; Estruch, Ramón; Ros, Emilio; Fitó, Montserrat; Arós, Fernando; Fiol, Miquel; Santos-Lozano, José Manuel; Serra-Majem, Lluís; Pintó, Xavier; Martínez-González, Miguel Ángel; Sorlí, José Vicente; Basora, Josep; Salas-Salvadó, Jordi

2018-04-16

Prospective studies have reported an inverse association between the consumption of total dairy products and milk and the risk of colorectal cancer (CRC). Nonetheless, there is little and inconsistent evidence regarding subtypes of dairy product and CRC risk. We assessed the associations between the consumption of total dairy products, their different subtypes and CRC risk in older Mediterranean individuals at high cardiovascular risk. We analyzed data from 7,216 men and women (55-80 years) without CRC at baseline from the PREvención con DIeta MEDiterránea study. Individuals were recruited between 2003 and 2009 and followed up until December 2012. At baseline and yearly thereafter, consumption of total and specific dairy products was assessed using a validated 137-item food-frequency questionnaire. Cox proportional hazards ratios (HRs) of CRC incidence were estimated for tertiles of mean consumption of dairy products during the follow-up. During a median [interquartile range] follow-up of 6.0 [4.4-7.3] years, we documented 101 incident CRC cases. In the multivariable-adjusted models, HRs and 95% confidence intervals (CIs) of CRC for the comparison of extreme tertiles of total dairy product and low-fat milk consumption were 0.55 (95% CI: 0.31-0.99; p-trend = 0.037) and 0.54 (95% CI: 0.32-0.92; p-trend = 0.022), respectively. No significant associations with other dairy products (whole-fat and low-fat dairy products; total, low-fat and whole-fat yogurt; cheese; total, low-fat and whole-fat milk; concentrated full-fat dairy products, sugar-enriched dairy products and fermented dairy products) were found. A high consumption of total dairy products and low-fat milk was significantly associated with a reduced CRC risk. © 2018 UICC.

Influence of the Hfq and Crc global regulators on the control of iron homeostasis in Pseudomonas putida.

Science.gov (United States)

Sánchez-Hevia, Dione L; Yuste, Luis; Moreno, Renata; Rojo, Fernando

2018-04-30

Metabolically versatile bacteria use catabolite repression control to select their preferred carbon sources, thus optimizing carbon metabolism. In pseudomonads, this occurs through the combined action of the proteins Hfq and Crc, which form stable tripartite complexes at target mRNAs, inhibiting their translation. The activity of Hfq/Crc is antagonised by small RNAs of the CrcZ family, the amounts of which vary according to carbon availability. The present work examines the role of Pseudomonas putida Hfq protein under conditions of low-level catabolite repression, in which Crc protein would have a minor role since it is sequestered by CrcZ/CrcY. The results suggest that, under these conditions, Hfq remains operative and plays an important role in iron homeostasis. In this scenario, Crc appears to participate indirectly by helping CrcZ/CrcY to control the amount of free Hfq in the cell. Iron homeostasis in pseudomonads relies on regulatory elements such as the Fur protein, the PrrF1-F2 sRNAs, and several extracytoplasmic sigma factors. Our results show that the absence of Hfq is paralleled by a reduction in PrrF1-F2 small RNAs. Hfq thus provides a regulatory link between iron and carbon metabolism, coordinating the iron supply to meet the needs of the enzymes operational under particular nutritional regimes. This article is protected by copyright. All rights reserved. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

Virulence of Pseudomonas syringae pv. tomato DC3000 Is Influenced by the Catabolite Repression Control Protein Crc.

Science.gov (United States)

Chakravarthy, Suma; Butcher, Bronwyn G; Liu, Yingyu; D'Amico, Katherine; Coster, Matthew; Filiatrault, Melanie J

2017-04-01

Pseudomonas syringae infects diverse plant species and is widely used as a model system in the study of effector function and the molecular basis of plant diseases. Although the relationship between bacterial metabolism, nutrient acquisition, and virulence has attracted increasing attention in bacterial pathology, it is largely unexplored in P. syringae. The Crc (catabolite repression control) protein is a putative RNA-binding protein that regulates carbon metabolism as well as a number of other factors in the pseudomonads. Here, we show that deletion of crc increased bacterial swarming motility and biofilm formation. The crc mutant showed reduced growth and symptoms in Arabidopsis and tomato when compared with the wild-type strain. We have evidence that the crc mutant shows delayed hypersensitive response (HR) when infiltrated into Nicotiana benthamiana and tobacco. Interestingly, the crc mutant was more susceptible to hydrogen peroxide, suggesting that, in planta, the mutant may be sensitive to reactive oxygen species generated during pathogen-associated molecular pattern-triggered immunity (PTI). Indeed, HR was further delayed when PTI-induced tissues were challenged with the crc mutant. The crc mutant did not elicit an altered PTI response in plants compared with the wild-type strain. We conclude that Crc plays an important role in growth and survival during infection.

Colorectal Cancer Risk in Patients With Lynch Syndrome and Inflammatory Bowel Disease

NARCIS (Netherlands)

Derikx, L.A.A.P.; Smits, L.J.T.; Lent-van Vliet, S. van; Dekker, E.; Aalfs, C.M.; Kouwen, M.C.A. van; Nagengast, F.M.; Nagtegaal, I.D.; Hoogerbrugge, N.; Hoentjen, F.

2017-01-01

Lynch syndrome and inflammatory bowel diseases (IBD) are associated with an increased risk of colorectal cancer (CRC). However, it is not clear whether the risk of CRC is even higher for patients with a combination of Lynch syndrome and IBD. We investigated the risk for CRC in this subgroup by

Interplay between the catabolite repression control protein Crc, Hfq and RNA in Hfq-dependent translational regulation in Pseudomonas aeruginosa.

Science.gov (United States)

Sonnleitner, Elisabeth; Wulf, Alexander; Campagne, Sébastien; Pei, Xue-Yuan; Wolfinger, Michael T; Forlani, Giada; Prindl, Konstantin; Abdou, Laetitia; Resch, Armin; Allain, Frederic H-T; Luisi, Ben F; Urlaub, Henning; Bläsi, Udo

2018-02-16

In Pseudomonas aeruginosa the RNA chaperone Hfq and the catabolite repression control protein (Crc) act as post-transcriptional regulators during carbon catabolite repression (CCR). In this regard Crc is required for full-fledged Hfq-mediated translational repression of catabolic genes. RNAseq based transcriptome analyses revealed a significant overlap between the Crc and Hfq regulons, which in conjunction with genetic data supported a concerted action of both proteins. Biochemical and biophysical approaches further suggest that Crc and Hfq form an assembly in the presence of RNAs containing A-rich motifs, and that Crc interacts with both, Hfq and RNA. Through these interactions, Crc enhances the stability of Hfq/Crc/RNA complexes, which can explain its facilitating role in Hfq-mediated translational repression. Hence, these studies revealed for the first time insights into how an interacting protein can modulate Hfq function. Moreover, Crc is shown to interfere with binding of a regulatory RNA to Hfq, which bears implications for riboregulation. These results are discussed in terms of a working model, wherein Crc prioritizes the function of Hfq toward utilization of favored carbon sources.

Obesity, Aspirin, and Risk of Colorectal Cancer in Carriers of Hereditary Colorectal Cancer

DEFF Research Database (Denmark)

Movahedi, Mohammad; Bishop, D Timothy; Macrae, Finlay

2015-01-01

PURPOSE: In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This prospective study investigated the association between body mass index and cancer risk...... was 25.0 months, and mean follow-up was 55.7 months. RESULTS: During follow-up, 55 of 937 participants developed CRC. For obese participants, CRC risk was 2.41× (95% CI, 1.22 to 4.85) greater than for underweight and normal-weight participants (reference group), and CRC risk increased by 7% for each 1-kg....../m(2) increase in body mass index. The risk of all LS-related cancers in obese people was 1.77× (95% CI, 1.06 to 2.96; P = .03) greater than for the reference group. In subgroup analysis, obesity was associated with 3.72× (95% CI, 1.41 to 9.81) greater CRC risk in patients with LS with MLH1 mutation...

CRC handbook of modern telecommunications

CERN Document Server

Morreale, Patricia A

2001-01-01

This authoritative handbook, contributed to by a team of international experts, covers the most dynamic areas in the changing telecommunications landscape. Written for telecommunications specialists who implement the new technologies, The CRC Handbook of Modern Telecommunications is an excellent companion volume to the authors' The Telecommunications Handbook, but stands well on its own, as it extends the range of topics to include voice over Internet, traffic management, quality of service, and other dominant future trends. It is an indispensable reference for all professionals working in the

Risk modification of colorectal cancer susceptibility by interleukin-8 -251T>A polymorphism in Malaysians.

Science.gov (United States)

Mustapha, Mohd Aminudin; Shahpudin, Siti Nurfatimah Mohd; Aziz, Ahmad Aizat Abdul; Ankathil, Ravindran

2012-06-07

To investigate the allele and genotype frequencies and associated risk of interleukin (IL)-8 -251T>A polymorphism on colorectal cancer (CRC) susceptibility risk. Peripheral blood samples of 255 normal controls and 255 clinically and histopathologically confirmed CRC patients were genotyped for IL-8 -251T>A polymorphism employing allele-specific polymerase chain reaction. The relative association of variant allele and genotypes with CRC susceptibility risk was determined by calculating the odds ratios (ORs). Corresponding χ² tests on the CRC patients and controls were carried out and 95% confidence intervals (CIs) were determined using Fisher's exact test. The allele frequencies and its risk association were calculated using FAMHAP, haplotype association analysis software. On comparing the frequencies of genotypes of patients and controls, the homozygous variant AA was significantly higher in CRC patients (P = 0.002) compared to controls. Investigation on the association of the polymorphic genotypes with CRC susceptibility risk, showed that the homozygous variant IL-8 -251AA had a significantly increased risk with OR 3.600 (95% CI: 1.550-8.481, P = 0.001). In the case of allele frequencies, variant allele A of IL-8 -251 showed a significantly increased risk of CRC predisposition with OR 1.32 (95% CI: 1.03-1.69, P = 0.003). Variant allele and genotype of IL-8 (-251T>A) was significantly associated with CRC susceptibility risk and could be considered as a high-risk variant for CRC predisposition.

Self reported awareness of child maltreatment among school professionals in Saudi Arabia: impact of CRC ratification.

Science.gov (United States)

AlBuhairan, Fadia S; Inam, Sarah S; AlEissa, Majid A; Noor, Ismail K; Almuneef, Maha A

2011-12-01

The Convention on the Rights of the Child (CRC) was ratified by Saudi Arabia 15 years ago; yet addressing the issue of child maltreatment only began in more recent years. School professionals play a significant role in children's lives, as they spend a great deal of time with them and are hence essential to protecting and identifying those in danger or at risk. The objective of this study is to identify school professional's awareness of child maltreatment and the existing national policies and procedures to examine the extent of efforts made in Saudi Arabia and to activate the roles of schools and school professionals in protecting children from violence and implementation of Article 19 of the CRC. This was a cross-sectional study, where school professionals from randomly selected schools throughout the country were invited to participate in a self-administered questionnaire. A total of 3,777 school professionals participated in the study. Fifty-five percent of professionals had at least 10 years of work experience. A low-level of awareness of child maltreatment was found in about 1/3 of school professionals. Only 1.9% of school professionals had ever attended any sort of specific training on child maltreatment, though 69.3% of those who had not, were willing to attend future training. With regards to awareness of CRC Article 19 or policies and procedures addressing child maltreatment, only 22% reported being aware of it. The majority of school professionals in Saudi Arabia have a low-intermediate level of awareness of child maltreatment, ratification of CRC, and related national policies and procedures, yet most are willing to attend training programs on this subject matter. Efforts need to be made in the country to fill this gap. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of smoking and antioxidant micronutrients on risk of colorectal cancer.

Science.gov (United States)

Hansen, Rikke Dalgaard; Albieri, Vanna; Tjønneland, Anne; Overvad, Kim; Andersen, Klaus Kaae; Raaschou-Nielsen, Ole

2013-04-01

Antioxidant intake has been reported to increase the risk of colorectal cancer (CRC) for smokers, yet reduce the risk for nonsmokers. We investigated the association between tobacco smoking and risk of colon or rectal cancer, and whether dietary and supplemental intake of the antioxidant vitamins A, C, E, β-carotene, selenium, zinc, and manganese affects the risk of CRC among smokers. Data on smoking habits and antioxidant intake were analyzed for 54,208 participants in the Danish Prospective Diet, Cancer and Health Study. Of these participants, 642 were diagnosed with colon cancer and 348 were diagnosed with rectal cancer. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazard models. Principal components were used to analyze intake of combinations of antioxidants. Ever smoking increased the risk for CRC (hazard ratio, 1.19; 95% confidence interval, 1.03-1.37), especially for rectal cancer. Smoking for at least 20 years was associated with a 26% increase in risk of CRC, compared with never smokers, and smoking 20 g tobacco or more each day was associated with a 30% increase in risk. Smoking for more than 30 years, or more than 20 g tobacco each day, was associated with a 48% increase in risk of rectal cancer. We did not observe an interaction between smoking and antioxidant consumption on risk of CRC. Tobacco smoking increases the risk for CRC. We did not observe that consumption of antioxidant micronutrients modulates the effects of smoking on CRC risk. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions.

Science.gov (United States)

Mohapatra, Shyam S; Batra, Surinder K; Bharadwaj, Srinivas; Bouvet, Michael; Cosman, Bard; Goel, Ajay; Jogunoori, Wilma; Kelley, Michael J; Mishra, Lopa; Mishra, Bibhuti; Mohapatra, Subhra; Patel, Bhaumik; Pisegna, Joseph R; Raufman, Jean-Pierre; Rao, Shuyun; Roy, Hemant; Scheuner, Maren; Singh, Satish; Vidyarthi, Gitanjali; White, Jon

2018-05-01

Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran population, a fact which has focused a great deal of the attention of the VA's research and development efforts. A field-based meeting of CRC experts was convened to discuss both challenges and opportunities in precision medicine for CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early detection and prevention. There was also a discussion of precision treatment involving fluorescence-guided surgery, targeted chemotherapies and immunotherapies, and personalized cancer treatment approaches. The overarching goal was to identify modalities that might ultimately lead to personalized cancer diagnosis and treatment. This review summarizes the findings of this VA field-based meeting, in which much of the current knowledge on CRC prescreening and treatment was discussed. It was concluded that there is a need and an opportunity to identify new targets for both the prevention of CRC and the development of effective therapies for advanced disease. Also, developing methods integrating genomic testing with tumoroid-based clinical drug response might lead to more accurate diagnosis and prognostication and more effective personalized treatment of CRC.

Therapeutic value of EGFR inhibition in CRC and NSCLC: 15 years of clinical evidence.

Science.gov (United States)

Troiani, Teresa; Napolitano, Stefania; Della Corte, Carminia Maria; Martini, Giulia; Martinelli, Erika; Morgillo, Floriana; Ciardiello, Fortunato

2016-01-01

Epidermal growth factor receptor (EGFR) plays a key role in tumour evolution, proliferation and immune evasion, and is one of the most important targets for biological therapy, especially for non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). In the past 15 years, several EGFR antagonists have been approved for the treatment of NSCLC and metastatic CRC (mCRC). To optimise the use of anti-EGFR agents in clinical practice, various clinical and molecular biomarkers have been investigated, thus moving their indication from unselected to selected populations. Nowadays, anti-EGFR drugs represent a gold-standard therapy for metastatic NSCLC harbouring EGFR activating mutation and for RAS wild-type mCRC. Their clinical efficacy is limited by the presence of intrinsic resistance or the onset of acquired resistance. In this review, we provide an overview of the antitumour activity of EGFR inhibitors in NSCLC and CRC and of mechanisms of resistance, focusing on the development of a personalised approach through 15 years of preclinical and clinical research.

MEG3 is a prognostic factor for CRC and promotes chemosensitivity by enhancing oxaliplatin-induced cell apoptosis.

Science.gov (United States)

Li, Lixia; Shang, Jian; Zhang, Yupeng; Liu, Shi; Peng, Yanan; Zhou, Zhou; Pan, Huaqing; Wang, Xiaobing; Chen, Lipng; Zhao, Qiu

2017-09-01

A major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to oxaliplatin-based chemotherapy. Recently, studies have shown that long non-coding RNAs (lncRNAs) play an important role in drug resistance. Using HiSeq sequencing methods, we identified that lncRNAs show differential expression levels in oxaliplatin-resistant (OxR) and non-resistant CRC patients. RT-qPCR was then performed in tissues and serum samples, and lncRNA MEG3 was verified to be downregulated in non-responding patients and to have considerable discriminating potential to identify responding patients from non-responding patients. Moreover, decreased serum MEG3 expression was associated with poor chemoresponse and low survival rate in CRC patients receiving oxaliplatin treatment. Subsequently, OxR cell lines were established, and MEG3 was significantly downregulated in HT29 OxR and SW480 OxR cells. In addition, overexpression of MEG3 with pMEG3 reversed oxaliplatin resistance in both CRC cell lines. Flow cytometric apoptosis analysis indicated that MEG3 promoted CRC cell apoptosis. More importantly, MEG3 enhanced oxaliplatin‑induced cell cytotoxicity in CRC. In conclusion, our integrated approach demonstrated that decreased expression of lncRNA MEG3 in CRC confers potent poor therapeutic efficacy, and that MEG3 promotes chemosensitivity by enhancing oxaliplatin-induced cell apoptosis. Thus, overexpression of MEG3 may be a future direction by which to develop a novel therapeutic strategy to overcome oxaliplatin resistance of CRC patients.

Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.

Science.gov (United States)

Sonnleitner, Elisabeth; Valentini, Martina; Wenner, Nicolas; Haichar, Feth el Zahar; Haas, Dieter; Lapouge, Karine

2012-01-01

The opportunistic human pathogen Pseudomonas aeruginosa is able to utilize a wide range of carbon and nitrogen compounds, allowing it to grow in vastly different environments. The uptake and catabolism of growth substrates are organized hierarchically by a mechanism termed catabolite repression control (Crc) whereby the Crc protein establishes translational repression of target mRNAs at CA (catabolite activity) motifs present in target mRNAs near ribosome binding sites. Poor carbon sources lead to activation of the CbrAB two-component system, which induces transcription of the small RNA (sRNA) CrcZ. This sRNA relieves Crc-mediated repression of target mRNAs. In this study, we have identified novel targets of the CbrAB/Crc system in P. aeruginosa using transcriptome analysis in combination with a search for CA motifs. We characterized four target genes involved in the uptake and utilization of less preferred carbon sources: estA (secreted esterase), acsA (acetyl-CoA synthetase), bkdR (regulator of branched-chain amino acid catabolism) and aroP2 (aromatic amino acid uptake protein). Evidence for regulation by CbrAB, CrcZ and Crc was obtained in vivo using appropriate reporter fusions, in which mutation of the CA motif resulted in loss of catabolite repression. CbrB and CrcZ were important for growth of P. aeruginosa in cystic fibrosis (CF) sputum medium, suggesting that the CbrAB/Crc system may act as an important regulator during chronic infection of the CF lung.

Macro- and Micronutrients Consumption and the Risk for Colorectal Cancer among Jordanians

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Reema F. Tayyem

2015-03-01

Full Text Available Objective: Diet and lifestyle have been reported to be important risk factors for the development of colorectal cancer (CRC. However, the association between total energy and nutrient intake and the risk of developing CRC has not been clearly explained. The aim of our study is to examine the relationship between total energy intake and other nutrients and the development of CRC in the Jordanian population. Research Methods and Procedures: Dietary data was collected from 169 subjects who were previously diagnosed with CRC, and 248 control subjects (matched by age, gender, occupation and marital status. These control subjects were healthy and disease free. Data was collected between January 2010 and December 2012, using interview-based questionnaires. Logistic regression was used to evaluate the association between quartiles of total energy, macro- and micronutrient intakes with the risk of developing CRC in our study population. Results: Total energy intake was associated with a higher risk of developing CRC (OR = 2.60 for the highest versus lowest quartile of intake; 95% CI: 1.21–5.56, p-trend = 0.03. Intakes of protein (OR = 3.62, 95% CI: 1.63–8.05, p-trend = 0.002, carbohydrates (OR = 1.41, 95% CI: 0.67–2.99, p-trend = 0.043, and percentage of energy from fat (OR = 2.10, 95% CI: 0.38–11.70, p-trend = 0.009 significantly increased the risk for the development of CRC. Saturated fat, dietary cholesterol and sodium intake showed a significant association with the risk of developing CRC (OR = 5.23, 95% CI: 2.33–11.76; OR = 2.48, 95% CI: 1.18–5.21; and OR = 3.42, 95% CI: 1.59–7.38, respectively, while vitamin E and caffeine intake were indicative of a protective effect against the development of CRC, OR = 0.002 (95% CI: 0.0003–0.011 and 0.023 (95%CI: 0.008–0.067, respectively. Conclusion: Our results suggest an increased risk for the development of CRC in subjects with high dietary intake of energy, protein, saturated fat

DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC.

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Liu, Yan-Ping; Zhu, Hui-Fang; Liu, Ding-Li; Hu, Zhi-Yan; Li, Sheng-Nan; Kan, He-Ping; Wang, Xiao-Yan; Li, Zu-Guo

2016-11-22

Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo. Conversely, DcR3 knockdown significantly repressed CRC cell proliferation and migration in vitro, and DcR3 deficiency also attenuated CRC tumorigenesis and metastasis in vivo. Functionally, DcR3 was essential for TGF-β3/SMAD-mediated epithelial-mesenchymal transition (EMT) of CRC cells. Importantly, cooperation between DcR3 and TGF-β3/SMAD-EMT signaling-related protein expression was correlated with survival and survival time in CRC patients. In conclusion, our results demonstrate that DcR3 may be a prognostic biomarker for CRC and that this receptor facilitates CRC development and metastasis by participating in TGF-β3/SMAD-mediated EMT of CRC cells.

Mucin Expression in Colorectal Cancer (CRC): Systematic Review and Meta-Analysis.

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Niv, Yaron; Rokkas, Theodore

2018-05-18

A body of evidence has suggested that mucins play an important role in adhesion, invasion, and cancer metastasis. However, this evidence is scarce and sometimes confusing. We performed a systematic review and meta-analysis of available studies to better define the role of mucins in the behavior of colorectal cancer (CRC). Medical literature was searched through November 30, 2017, using suitable keywords. Pooled estimates, that is, odd ratios (ORs), were obtained using fixed or random-effects models, as appropriate. Heterogeneity between studies was evaluated with the Cochran Q test and I values, whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the Begg and Mazumdar adjusted rank correlation test and by the Egger regression test. A total of 2234 CRC patients were included in 12 studies, eligible for meta-analysis. There was a significant difference concerning total mucin expression between CRC patients and controls [pooled ORs (95% confidence interval)=8.156 (2.624-25.354), test for overall effect Z=3.627, PCRC, that is advanced stage versus localized disease [ORs (95% confidence interval)=2.724 (1.211-6.127), Z= 2.423, P=0.015], as opposed to MUC2 and MUC4. MUC1 is overexpressed in CRC tissue comparing with healthy mucosa, and may have a role in the neoplastic transformation and metastatic process. MUC2 has probably no role in carcinogenesis.

Strongly enhanced colorectal cancer risk stratification by combining family history and genetic risk score

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Weigl K

2018-01-01

Full Text Available Korbinian Weigl,1,2 Jenny Chang-Claude,3,4 Phillip Knebel,5 Li Hsu,6 Michael Hoffmeister,1 Hermann Brenner1,2,7 1Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ, Heidelberg, 2German Cancer Consortium (DKTK, German Cancer Research Center (DKFZ, Heidelberg, 3Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ, Heidelberg, 4University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, 5Department for General, Visceral and Transplantation Surgery, University Heidelberg, Heidelberg, Germany; 6Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 7Division of Preventive Oncology, German Cancer Research Center (DKFZ and National Center for Tumor Diseases (NCT, Heidelberg, Germany Background and aim: Family history (FH and genetic risk scores (GRSs are increasingly used for risk stratification for colorectal cancer (CRC screening. However, they were mostly considered alternatively rather than jointly. The aim of this study was to assess the potential of individual and joint risk stratification for CRC by FH and GRS.Patients and methods: A GRS was built based on the number of risk alleles in 53 previously identified single-nucleotide polymorphisms among 2,363 patients with a first diagnosis of CRC and 2,198 controls in DACHS [colorectal cancer: chances for prevention through screening], a population-based case-control study in Germany. Associations between GRS and FH with CRC risk were quantified by multiple logistic regression.Results: A total of 316 cases (13.4% and 214 controls (9.7% had a first-degree relative (FDR with CRC (adjusted odds ratio [aOR] 1.86, 95% CI 1.52–2.29. A GRS in the highest decile was associated with a 3.0-fold increased risk of CRC (aOR 3.00, 95% CI 2.24–4.02 compared with the lowest decile. This association was tentatively more pronounced in older age groups. FH and GRS were essentially unrelated, and their

Role of genetic & environment risk factors in the aetiology of colorectal cancer in Malaysia

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Nurul Hanis Ramzi

2014-01-01

Full Text Available Background & objectives: Colorectal cancer (CRC is second only to breast cancer as the leading cause of cancer-related deaths in Malaysia. In the Asia-Pacific area, it is the highest emerging gastrointestinal cancer. The aim of this study was to identify single nucleotide polymorphisms (SNPs and environmental factors associated with CRC risk in Malaysia from a panel of cancer associated SNPs. Methods: In this case-control study, 160 Malaysian subjects were recruited, including both with CRC and controls. A total of 768 SNPs were genotyped and analyzed to distinguish risk and protective alleles. Genotyping was carried out using Illumina′s BeadArray platform. Information on blood group, occupation, medical history, family history of cancer, intake of red meat and vegetables, exposure to radiation, smoking and drinking habits, etc was collected. Odds ratio (OR, 95% confidence interval (CI were calculated. Results: A panel of 23 SNPs significantly associated with colorectal cancer risk was identified ( p0 <0.01. Of these, 12 SNPs increased the risk of CRC and 11 reduced the risk. Among the environmental risk factors investigated, high intake of red meat (more than 50% daily proportion was found to be significantly associated with increased risk of CRC (OR=6.52, 95% CI :1.93 - 2.04, P=0.003. Two SNPs including rs2069521 and rs10046 in genes of cytochrome P450 (CYP superfamily were found significantly associated with CRC risk. For gene-environment analysis, the A allele of rs2069521 showed a significant association with CRC risk when stratified by red meat intake. Interpretation & conclusions: In this preliminary study, a panel of SNPs found to be significantly associated with CRC in Malaysian population, was identified. Also, red meat consumption and lack of physical exercise were risk factors for CRC, while consumption of fruits and vegetables served as protective factor.

The more from East-Asian, the better: risk prediction of colorectal cancer risk by GWAS-identified SNPs among Japanese.

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Abe, Makiko; Ito, Hidemi; Oze, Isao; Nomura, Masatoshi; Ogawa, Yoshihiro; Matsuo, Keitaro

2017-12-01

Little is known about the difference of genetic predisposition for CRC between ethnicities; however, many genetic traits common to colorectal cancer have been identified. This study investigated whether more SNPs identified in GWAS in East Asian population could improve the risk prediction of Japanese and explored possible application of genetic risk groups as an instrument of the risk communication. 558 Patients histologically verified colorectal cancer and 1116 first-visit outpatients were included for derivation study, and 547 cases and 547 controls were for replication study. Among each population, we evaluated prediction models for the risk of CRC that combined the genetic risk group based on SNPs from GWASs in European-population and a similarly developed model adding SNPs from GWASs in East Asian-population. We examined whether adding East Asian-specific SNPs would improve the discrimination. Six SNPs (rs6983267, rs4779584, rs4444235, rs9929218, rs10936599, rs16969681) from 23 SNPs by European-based GWAS and five SNPs (rs704017, rs11196172, rs10774214, rs647161, rs2423279) among ten SNPs by Asian-based GWAS were selected in CRC risk prediction model. Compared with a 6-SNP-based model, an 11-SNP model including Asian GWAS-SNPs showed improved discrimination capacity in Receiver operator characteristic analysis. A model with 11 SNPs resulted in statistically significant improvement in both derivation (P = 0.0039) and replication studies (P = 0.0018) compared with six SNP model. We estimated cumulative risk of CRC by using genetic risk group based on 11 SNPs and found that the cumulative risk at age 80 is approximately 13% in the high-risk group while 6% in the low-risk group. We constructed a more efficient CRC risk prediction model with 11 SNPs including newly identified East Asian-based GWAS SNPs (rs704017, rs11196172, rs10774214, rs647161, rs2423279). Risk grouping based on 11 SNPs depicted lifetime difference of CRC risk. This might be useful for

DEAD-box helicase 27 promotes colorectal cancer growth and metastasis and predicts poor survival in CRC patients.

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Tang, Jieting; Chen, Huarong; Wong, Chi-Chun; Liu, Dabin; Li, Tong; Wang, Xiaohong; Ji, Jiafu; Sung, Joseph Jy; Fang, Jing-Yuan; Yu, Jun

2018-03-14

Copy number alterations (CNAs) are crucial for colorectal cancer (CRC) development. In this study, DEAD box polypeptide 27 (DDX27) was identified to be highly amplified in both TCGA CRC (474/615) and primary CRC (47/103), which was positively correlated with its mRNA overexpression. High DDX27 mRNA (N = 199) and protein expression (N = 260) predicted poor survival in CRC patients. Ectopic expression of DDX27 increased CRC cells proliferation, migration and invasion, but suppressed apoptosis. Conversely, silencing of DDX27 exerted opposite effects in vitro and significantly inhibited murine xenograft tumor growth and lung metastasis in vivo. Up-regulation of DDX27 enhanced and prolonged TNF-α-mediated NF-κB signaling. Nucleophosmin (NPM1) was identified as a binding partner of DDX27. DDX27 increased nuclear NPM1 and NF-κB-p65 interaction to enhance DNA binding activity of NF-κB. Silencing NPM1 abrogated DDX27-activating NF-κB signaling and its tumor-promoting function. Together, DDX27 is overexpressed and plays a pivotal oncogenic role in CRC.

miR-133b down-regulates ABCC1 and enhances the sensitivity of CRC to anti-tumor drugs.

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Chen, Miao; Li, Daojiang; Gong, Ni; Wu, Hao; Su, Chen; Xie, Canbin; Xiang, Hong; Lin, Changwei; Li, Xiaorong

2017-08-08

Multidrug resistance (MDR) is the main cause of failed chemotherapy treatments. Therefore, preventing MDR is pivotal in treating colorectal cancer (CRC). In a previous study miR-133b was shown to be a tumor suppressor. Additionally, in CRC cells transfected with miR-133b, ATP-binding cassette (ABC) subfamily C member 1(ABCC1) was shown to be significantly down regulated. Whether miR-133b also enhances the chemosensitivity of drugs used to treat CRC by targeting ABCC1 is still unclear. Here, we utilized flow cytometry and high-performance liquid chromatography (HPLC) analysis to identify the ability of miR-133b to reserve MDR in CRC. We then used a dual-luciferase reporter assay to validate that miR-133b targets ABCC1. Further in vivo experiments were designed to validate the method in which miR-133b reversed MDR in CRC cells. The results demonstrated that the level of miR-133b was down-regulated and the expression of ABCC1 was up-regulated in drug-resistant CRC cells compared to non-drug-resistant CRC cells. The restoration of miR-133b expression in CRC drug-resistant cells in vitro resulted in reduced IC50s to chemotherapeutic drugs, significantly induced G1 accumulation, inhibited growth and promoted necrosis in combination with either 5-fluorouracil (5-FU) or vincristine (VCR), and decreased the expression of ABCC1. The dual-luciferase assay demonstrated that miR-133b directly targets ABCC1. The combination of agomiRNA-133b with chemotherapeutic drugs in vivo inhibited tumor growth induced by CRC drug-resistant cells. A xenograft from the in vivo model resulted in up-regulated levels of miR-133b and down-regulated levels of ABCC1. Therefore, miR-133b enhances the chemosensitivity of CRC cells to anti-tumor drugs by directly down-regulating ABCC1. This discovery provides a therapeutic strategy in which miR-133b is used as a potential sensitizer for drug-resistant CRC.

The New Zealand PIPER Project: colorectal cancer survival according to rurality, ethnicity and socioeconomic deprivation-results from a retrospective cohort study.

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Sharples, Katrina J; Firth, Melissa J; Hinder, Victoria A; Hill, Andrew G; Jeffery, Mark; Sarfati, Diana; Brown, Charis; Atmore, Carol; Lawrenson, Ross A; Reid, Papaarangi Mj; Derrett, Sarah L; Macapagal, Jerome; Keating, John P; Secker, Adrian H; De Groot, Charles; Jackson, Christopher Gca; Findlay, Michael Pn

2018-06-08

To investigate differences in survival after diagnosis with colorectal cancer (CRC) by rurality, ethnicity and deprivation. In this retrospective cohort study, clinical records and National Collections data were merged for all patients diagnosed with CRC in New Zealand in 2007-2008. Prioritised ethnicity was classified using New Zealand Cancer Registry data; meshblock of residence at diagnosis was used to determine rurality and socioeconomic deprivation. Of the 4,950 patients included, 1,938 had died of CRC by May 2014. The five-year risks of death from CRC were: Māori 47%; Pacific 59%; non-Māori-non-Pacific (nMnP) 38%. After adjustment for demographic characteristics, comorbidity and disease stage at diagnosis, compared to nMnP the relative risk (RR) for Māori was 1.1 (95%CI: 0.8-1.3) and for Pacific 1.8 (95% CI: 1.4-2.5). We found no differences in risk of death from CRC by rurality, but some differences by deprivation. Disparity in outcome following diagnosis with CRC exists in New Zealand. Much of this disparity can be explained by stage of disease at diagnosis for Māori, but for Pacific peoples and those in deprived areas other factors may influence outcome. Further analyses of the PIPER data will explore the impact of any differences in management.

The CRC 20 years: An overview of some of the major achievements and remaining challenges.

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Doek, Jaap E

2009-11-01

On 20 November 1989, the General Assembly of the United Nations adopted the Convention on the Rights of the Child (CRC). It entered into force on 2 September 1990 and has by now been ratified by 193 States, making the most universally ratified human rights treaty. This overview will present and discuss the impact of this treaty both at the international and the national level, an overview which necessarily has to be limited to some of the developments as a result of the implementation of the CRC. The first part of this paper will be devoted to the impact the CRC had and still has on the setting and development of the international agenda for the promotion and protection of the rights and welfare of children. Special attention will given to developments, achievements, and remaining challenges at the international level with regard to protection of children in armed conflict; prevention and the protection of children from sexual exploitation; and from all forms of violence. This will include some information on the impact of these international developments and actions at the national level, for example, in the area of legislation. The second part will focus on the impact at the national level. Given the wide scope of the CRC this part will be limited to some of the General Measures of Implementation (law reform, national programmes, and independent monitoring) and the General Principles (non-discrimination, best interest, right to be heard) of the CRC. This will be based on reports of States on the implementation of the CRC submitted to the CRC Committee and the Concluding Observations of this Committee and on a number of studies. The conclusion will provide remarks on poverty as one of the major remaining challenges for the implementation of children's rights.

Low Complexity List Decoding for Polar Codes with Multiple CRC Codes

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Jong-Hwan Kim

2017-04-01

Full Text Available Polar codes are the first family of error correcting codes that provably achieve the capacity of symmetric binary-input discrete memoryless channels with low complexity. Since the development of polar codes, there have been many studies to improve their finite-length performance. As a result, polar codes are now adopted as a channel code for the control channel of 5G new radio of the 3rd generation partnership project. However, the decoder implementation is one of the big practical problems and low complexity decoding has been studied. This paper addresses a low complexity successive cancellation list decoding for polar codes utilizing multiple cyclic redundancy check (CRC codes. While some research uses multiple CRC codes to reduce memory and time complexity, we consider the operational complexity of decoding, and reduce it by optimizing CRC positions in combination with a modified decoding operation. Resultingly, the proposed scheme obtains not only complexity reduction from early stopping of decoding, but also additional reduction from the reduced number of decoding paths.

Pro-inflammatory fatty acid profile and colorectal cancer risk: A Mendelian randomisation analysis.

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May-Wilson, Sebastian; Sud, Amit; Law, Philip J; Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hänninen, Ulrika A; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Sarin, Antti-Pekka; Eriksson, Johan G; Rissanen, Harri; Knekt, Paul; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A; Palles, Claire; Farrington, Susan M; Timofeeva, Maria N; Meyer, Brian F; Wakil, Salma M; Campbell, Harry; Smith, Christopher G; Idziaszczyk, Shelley; Maughan, Timothy S; Fisher, David; Kerr, Rachel; Kerr, David; Passarelli, Michael N; Figueiredo, Jane C; Buchanan, Daniel D; Win, Aung K; Hopper, John L; Jenkins, Mark A; Lindor, Noralane M; Newcomb, Polly A; Gallinger, Steven; Conti, David; Schumacher, Fred; Casey, Graham; Aaltonen, Lauri A; Cheadle, Jeremy P; Tomlinson, Ian P; Dunlop, Malcolm G; Houlston, Richard S

2017-10-01

While dietary fat has been established as a risk factor for colorectal cancer (CRC), associations between fatty acids (FAs) and CRC have been inconsistent. Using Mendelian randomisation (MR), we sought to evaluate associations between polyunsaturated (PUFA), monounsaturated (MUFA) and saturated FAs (SFAs) and CRC risk. We analysed genotype data on 9254 CRC cases and 18,386 controls of European ancestry. Externally weighted polygenic risk scores were generated and used to evaluate associations with CRC per one standard deviation increase in genetically defined plasma FA levels. Risk reduction was observed for oleic and palmitoleic MUFAs (OR OA  = 0.77, 95% CI: 0.65-0.92, P = 3.9 × 10 -3 ; OR POA  = 0.36, 95% CI: 0.15-0.84, P = 0.018). PUFAs linoleic and arachidonic acid had negative and positive associations with CRC respectively (OR LA  = 0.95, 95% CI: 0.93-0.98, P = 3.7 × 10 -4 ; OR AA  = 1.05, 95% CI: 1.02-1.07, P = 1.7 × 10 -4 ). The SFA stearic acid was associated with increased CRC risk (OR SA  = 1.17, 95% CI: 1.01-1.35, P = 0.041). Results from our analysis are broadly consistent with a pro-inflammatory FA profile having a detrimental effect in terms of CRC risk. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Consumption of Cigarettes but not Betel Quid or Alcohol Increases Colorectal Cancer Risk

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I-Chen Wu

2009-02-01

Conclusion: Our results indicated that consumption of cigarettes but not betel quid or alcohol was a risk factor for male CRC. A large study is necessary to investigate the risk factors for female CRC in Taiwan, and to understand the effect of betel quid exposure on male CRC.

Combination of preoperative NLR, PLR and CEA could increase the diagnostic efficacy for I-III stage CRC.

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Peng, Hong-Xin; Yang, Lin; He, Bang-Shun; Pan, Yu-Qin; Ying, Hou-Qun; Sun, Hui-Ling; Lin, Kang; Hu, Xiu-Xiu; Xu, Tao; Wang, Shu-Kui

2017-09-01

Inflammation plays an important role in the development and progression of CRC. The members of inflammatory biomarkers, preoperative NLR and PLR, have been proved by numerous studies to be promising prognostic biomarkers for CRC. However, the diagnostic value of the two biomarkers in CRC remains unknown, and no study reported the combined diagnostic efficacy of NLR, PLR and CEA. Five hundred and fifty-nine patients with I-III stage CRC undergoing surgical resection and 559 gender- and age-matched healthy controls were enrolled in this retrospective study. NLR and PLR were calculated from preoperative peripheral blood cell count detected using white blood cell five classification by Sysmex XT-1800i Automated Hematology System and serum CEA were measured by electrochemiluminescence by ELECSYS 2010. The diagnostic performance of NLR, PLR and CEA for CRC was evaluated by ROC curve. Levels of NLR and PLR in the cases were significantly higher than them in the healthy controls. ROC curves comparison analyses showed that the diagnostic efficacy of NLR (AUC=.755, 95%CI=.728-.780) alone for CRC was significantly higher than PLR (AUC=.723, 95%CI=.696-.749, P=.037) and CEA (AUC=.690, 95%CI=.662-.717, P=.002) alone. In addition, the diagnostic efficacy of the combination of NLR, PLR and CEA(AUC=.831, 95%CI=.807-.852)for CRC was not only significantly higher than NLR alone but also higher than any combinations of the two of these three biomarkers (PCRC diagnostic biomarker, even for early stage CRC, and the combination of NLR, PLR and CEA could significantly improve the diagnostic efficacy. © 2016 Wiley Periodicals, Inc.

IRRIGATION PRACTICES IN LONG-TERM SURVIVORS OF COLORECTAL CANCER (CRC) WITH COLOSTOMIES

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Grant, Marcia; McMullen, Carmit K.; Altschuler, Andrea; Hornbrook, Mark C.; Herrinton, Lisa J.; Wendel, Christopher S.; Baldwin, Carol M.; Krouse, Robert S.

2012-01-01

Creation of a colostomy in colorectal (CRC) cancer patients results in a loss of control over bowel evacuation. The only way to re-establish some control is through irrigation, a procedure that involves instilling fluid into the bowel to allow for gas and fecal output. This article reports on irrigation practices of participants in a large, multi-site, multi-investigator study of health-related quality of life (HR-QOL) in long term CRC survivors. Questions about irrigation practices were iden...

Nitrate in drinking water and risk of colorectal cancer in Yogyakarta, Indonesia.

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Fathmawati; Fachiroh, Jajah; Gravitiani, Evi; Sarto; Husodo, Adi Heru

2017-01-01

Nitrate concentration in well water in Yogyakarta, Indonesia, and its surroundings tended to increase rapidly from time to time, and it may be associated with an elevated risk for several types of cancer. The purpose of this study was to examine the association between nitrate in drinking water and colorectal cancer (CRC) risk occurrence. A case-control study was conducted in Yogyakarta Special Province. Pathologically confirmed 75 CRC patients and 75 controls were consulted and their individual well water was sampled and examined for nitrate concentrations. Logistic regression analysis was conducted to establish the association between nitrate and CRC risk development. There was a significant correlation between nitrate in drinking water and CRC occurrence, and this value was relatively stable after being adjusted for protein intake, smoking history, age, and family history of cancer. These findings demonstrated that the risk of CRC development was fourfold among those with >10 years of nitrate exposure from well water compared with those with ≤10 years of nitrate exposure. Consequently, a significant association between nitrate in drinking water and occurrence of CRC in Yogyakarta was established.

Influence of the Crc regulator on the hierarchical use of carbon sources from a complete medium in Pseudomonas.

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La Rosa, Ruggero; Behrends, Volker; Williams, Huw D; Bundy, Jacob G; Rojo, Fernando

2016-03-01

The Crc protein, together with the Hfq protein, participates in catabolite repression in pseudomonads, helping to coordinate metabolism. Little is known about how Crc affects the hierarchy of metabolite assimilation from complex mixtures. Using proton Nuclear Magnetic Resonance (NMR) spectroscopy, we carried out comprehensive metabolite profiling of culture supernatants (metabolic footprinting) over the course of growth of both Pseudomonas putida and P. aeruginosa, and compared the wild-type strains with deletion mutants for crc. A complex metabolite consumption hierarchy was observed, which was broadly similar between the two species, although with some important differences, for example in sugar utilization. The order of metabolite utilization changed upon inactivation of the crc gene, but even in the Crc-null strains some compounds were completely consumed before late metabolites were taken up. This suggests the presence of additional regulatory elements that determine the time and order of consumption of compounds. Unexpectedly, the loss of Crc led both species to excrete acetate and pyruvate as a result of unbalanced growth during exponential phase, compounds that were later consumed in stationary phase. This loss of carbon during growth helps to explain the contribution of the Crc/Hfq regulatory system to evolutionary fitness of pseudomonads. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

NSC30049 inhibits Chk1 pathway in 5-FU-resistant CRC bulk and stem cell populations.

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Narayan, Satya; Jaiswal, Aruna S; Sharma, Ritika; Nawab, Akbar; Duckworth, Lizette Vila; Law, Brian K; Zajac-Kaye, Maria; George, Thomas J; Sharma, Jay; Sharma, Arun K; Hromas, Robert A

2017-08-22

The 5-fluorouracil (5-FU) treatment induces DNA damage and stalling of DNA replication forks. These stalled replication forks then collapse to form one sided double-strand breaks, leading to apoptosis. However, colorectal cancer (CRC) stem cells rapidly repair the stalled/collapsed replication forks and overcome treatment effects. Recent evidence suggests a critical role of checkpoint kinase 1 (Chk1) in preventing the replicative stress. Therefore, Chk1 kinase has been a target for developing mono or combination therapeutic agents. In the present study, we have identified a novel orphan molecule NSC30049 (NSC49L) that is effective alone, and in combination potentiates 5-FU-mediated growth inhibition of CRC heterogeneous bulk and FOLFOX-resistant cell lines in culture with minimal effect on normal colonic epithelial cells. It also inhibits the sphere forming activity of CRC stem cells, and decreases the expression levels of mRNAs of CRC stem cell marker genes. Results showed that NSC49L induces 5-FU-mediated S-phase cell cycle arrest due to increased load of DNA damage and increased γ-H2AX staining as a mechanism of cytotoxicity. The pharmacokinetic analysis showed a higher bioavailability of this compound, however, with a short plasma half-life. The drug is highly tolerated by animals with no pathological aberrations. Furthermore, NSC49L showed very potent activity in a HDTX model of CRC stem cell tumors either alone or in combination with 5-FU. Thus, NSC49L as a single agent or combined with 5-FU can be developed as a therapeutic agent by targeting the Chk1 pathway in 5-FU-resistant CRC heterogeneous bulk and CRC stem cell populations.

CRC Credential Attainment by State Vocational Rehabilitation Counselors

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Harpster, Anna M.; Byers, Katherine L.; Harris, LaKeisha L.

2011-01-01

This study examines 137 state vocational rehabilitation (VR) counselors' perceptions of the value of having the Certified Rehabilitation Counselor (CRC) credential. While almost 53% of this sample included persons who were certified, the majority who were not indicated that the two major reasons for not currently having this designation were: (a)…

Index-Based Dietary Patterns and Colorectal Cancer Risk: A Systematic Review123

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Steck, Susan E; Guinter, Mark; Zheng, Jiali; Thomson, Cynthia A

2015-01-01

Colorectal cancer (CRC) is the third most common cancer in both men and women in the United States. Various a priori dietary patterns that take into account diet complexity have been associated with CRC risk. This systematic review augments the evidence for an association between CRC risk and the Mediterranean Diet Score (MDS) and the Healthy Eating Index (HEI), and provides new evidence for a novel Dietary Inflammatory Index (DII). Human studies published in English after 31 December 2008 were reviewed. Five case-control studies and 7 prospective cohort studies conducted in the United States and Europe were identified. Five of the studies examined the MDS, 4 examined the HEI, and 4 examined the DII. Comparing highest to lowest score groups, higher MDSs were associated with an 8–54% lower CRC risk, and higher HEI scores were associated with a 20–56% lower CRC risk. More proinflammatory diet scores were associated with a 12–65% higher CRC risk compared with more anti-inflammatory diets in studies that used the DII. The results reported by sex suggested similar associations for men and women. This review builds upon the evidence supporting the association between higher overall diet quality and lower risk of CRC. Increasing scores of MDS and HEI and anti-inflammatory DII scores are characterized by high intake of plant-based foods and low intake of animal products. Future studies in more diverse populations and with consistent scoring calculations are recommended. PMID:26567200

NONLINEAR ASTEROSEISMOLOGY OF RR LYRAE

Energy Technology Data Exchange (ETDEWEB)

Molnar, L.; Kollath, Z.; Szabo, R. [Konkoly Observatory, MTA CSFK, H-1121 Budapest, Konkoly Thege Miklos ut 15-17 (Hungary); Bryson, S.; Mullally, F.; Thompson, S. E. [NASA Ames Research Center, MS 244-30, Moffet Field, CA 94035 (United States); Kolenberg, K., E-mail: molnar.laszlo@csfk.mta.hu [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge MA 02138 (United States)

2012-09-20

The observations of the Kepler Space Telescope revealed that fundamental-mode RR Lyrae stars may show various radial overtones. The presence of multiple radial modes may allow us to conduct nonlinear asteroseismology: comparison of mode amplitudes and frequency shifts between observations and models. Here we report the detection of three radial modes in the star RR Lyr, the eponym of the class, using the Kepler short cadence data: besides the fundamental mode, both the first and the ninth overtones can be derived from the data set. RR Lyrae shows period doubling, but switches occasionally to a state where a pattern of six pulsation cycles repeats instead of two. We found hydrodynamic models that show the same three modes and the period-six state, allowing for comparison with the observations.

Structural stability, electronic, mechanical and superconducting properties of CrC and MoC

Energy Technology Data Exchange (ETDEWEB)

Kavitha, M.; Sudha Priyanga, G. [Department of Physics, N.M.S.S.V.N College, Madurai 625019, Tamilnadu (India); Rajeswarapalanichamy, R., E-mail: rrpalanichamy@gmail.com [Department of Physics, N.M.S.S.V.N College, Madurai 625019, Tamilnadu (India); Iyakutti, K. [Department of Physics and Nanotechnology, SRM University, Chennai 603203, Tamilnadu (India)

2016-02-01

The structural, electronic, mechanical and superconducting properties of chromium carbide (CrC) and molybdenum carbide (MoC) are investigated using first principles calculations based on density functional theory (DFT). The computed ground state properties like equilibrium lattice constants and cell volume are in good agreement with available theoretical and experimental data. A pressure induced structural phase transition from tungsten carbide phase (WC) to zinc blende phase (ZB) and then zinc blende phase (ZB) to nickel arsenide phase (NiAs) are observed in both chromium and molybdenum carbides. Electronic structure reveals that these carbides are metallic at ambient condition. All the calculated elastic constants obey the Born–Huang stability criteria, suggesting that they are mechanically stable at normal and high pressure. The super conducting transition temperatures for CrC and MoC in WC phase are found to be 31.12 K and 17.14 K respectively at normal pressure. - Highlights: • Electronic and mechanical properties of CrC and MoC are investigated. • Pressure induced structural phase transition is predicted at high pressure. • Electronic structure reveals that these materials exhibit metallic behaviour. • Debye temperature values are computed for CrC and MoC. • Superconducting transition temperature values are computed.

RR Lyrae Stars in M4

Science.gov (United States)

Kuehn, Charles A.; Moskalik, Pawel; Drury, Jason A.

2017-10-01

Observations by Kepler/K2 have revolutionized the study of RR Lyrae stars by allowing the detection of new phenomna, such as low amplitude additional modes and period doubling, which had not previously been seen from the ground. During campaign 2, K2 observed the globular cluster M4, providiing the first opportunity to study a sizeable group of RR Lyrae stars that belong to a single population; the other RR Lyrae stars that have been observed from space are field stars in the galactic halo and thus belong to an assortment of populations. In this poster we present the results of our study of the RR Lyrae variables in M4 from K2 photometry. We have identified additional, low amplitude pulsation modes in both observed RRc stars. In 3 RRab stars we have found the Blazhko effect with periods of 16.6d, 22.4d, and 44.5d.

RR Lyrae Stars in M4

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Kuehn Charles A

2017-01-01

Full Text Available Observations by Kepler/K2 have revolutionized the study of RR Lyrae stars by allowing the detection of new phenomna, such as low amplitude additional modes and period doubling, which had not previously been seen from the ground. During campaign 2, K2 observed the globular cluster M4, providiing the first opportunity to study a sizeable group of RR Lyrae stars that belong to a single population; the other RR Lyrae stars that have been observed from space are field stars in the galactic halo and thus belong to an assortment of populations. In this poster we present the results of our study of the RR Lyrae variables in M4 from K2 photometry. We have identified additional, low amplitude pulsation modes in both observed RRc stars. In 3 RRab stars we have found the Blazhko effect with periods of 16.6d, 22.4d, and 44.5d.

Multicenter retrospective analysis of metastatic colorectal cancer (CRC) with high-level microsatellite instability (MSI-H).

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Goldstein, J; Tran, B; Ensor, J; Gibbs, P; Wong, H L; Wong, S F; Vilar, E; Tie, J; Broaddus, R; Kopetz, S; Desai, J; Overman, M J

2014-05-01

The microsatellite instability-high (MSI-H) phenotype, present in 15% of early colorectal cancer (CRC), confers good prognosis. MSI-H metastatic CRC is rare and its impact on outcomes is unknown. We describe survival outcomes and the impact of chemotherapy, metastatectomy, and BRAF V600E mutation status in the largest reported cohort of MSI-H metastatic colorectal cancer (CRC). A retrospective review of 55 MSI-H metastatic CRC patients from two institutions, Royal Melbourne Hospital (Australia) and The University of Texas MD Anderson Cancer Center (United States), was conducted. Statistical analyses utilized Kaplan-Meier method, Log-rank test, and Cox proportional hazards models. Median age was 67 years (20-90), 58% had poor differentiation, and 45% had stage IV disease at presentation. Median overall survival (OS) from metastatic disease was 15.4 months. Thirteen patients underwent R0/R1 metastatectomies, with median OS from metastatectomy 33.8 months. Thirty-one patients received first-line systemic chemotherapy for metastatic disease with median OS from the start of chemotherapy 11.5 months. No statistically significant difference in progression-free survival or OS was seen between fluoropyrimidine, oxaliplatin, or irinotecan based chemotherapy. BRAF V600E mutation was present in 14 of 47 patients (30%). BRAF V600E patients demonstrated significantly worse median OS; 10.1 versus 17.3 months, P = 0.03. In multivariate analyses, BRAF V600E mutants had worse OS (HR 4.04; P = 0.005), while patients undergoing metastatectomy (HR 0.11; P = CRC do not appear to have improved outcomes. BRAF V600E mutation is a poor prognostic factor in MSI-H metastatic CRC.

Association of estrogen receptor beta variants and serum levels of estradiol with risk of colorectal cancer: a case control study

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Wu Huanlei

2012-07-01

Full Text Available Abstract Background Endogenous estrogens may play a vital role in colorectal tumorigenesis. Estrogen receptor beta is the predominant subtype which mediates the biological effect of estrogens, while loss of expression of estrogen receptor beta has been indicated as a common step in the development of colorectal cancer (CRC. Epidemiological studies have revealed several functional polymorphisms of estrogen receptor beta (ESR2 for cancer risk, but relevant study in CRC is limited, particularly in men. This study aimed to investigate the association of circulating estradiol and variations of ESR2 with CRC risk in men. Methods We initiated a case–control study consisting of 390 patients with CRC and 445 healthy controls in men only. We genotyped ESR2 single nucleotide polymorphisms (SNPs rs1256049 and rs4986938 and measured serum estradiol concentration using chemilluminescence immunoassay. Multivariable logistic regression model was performed to evaluate the associations between these variables and CRC risk. Results ESR2 rs1256049 CT/TT genotypes were associated with reduced risk of CRC (odds ratio [OR], 0.7, 95% confidence interval [CI], 0.5–1.0, while rs4986938 CT/TT genotypes were associated with increased risk of CRC (OR, 1.5, 95% CI, 1.0–2.1. In addition, the CRC risk increased with the number of risk genotypes of these two SNPs in a dose–response manner (Ptrend, 0.003. Specifically, subjects carrying risk genotypes of both SNPs had the highest risk of CRC (OR, 2.0, 95% CI, 1.3–3.3.. Moreover, serum estradiol concentration alone was associated with risk of CRC in men (OR, 1.2, 95% CI, 1.0–1.3. However, individuals presenting both rs4986938 CT/TT genotypes and high level of serum estradiol had a high risk of CRC (OR, 2.3, 95% CI, 1.4–3.9, compared with those presenting CC genotype and low level of serum estradiol. The similar joint results were not observed for SNP rs1256049. Conclusions These results suggest that endogenous

Colorectal Cancer Risk in Patients With Lynch Syndrome and Inflammatory Bowel Disease.

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Derikx, Lauranne A A P; Smits, Lisa J T; van Vliet, Shannon; Dekker, Evelien; Aalfs, Cora M; van Kouwen, Mariëtte C A; Nagengast, Fokko M; Nagtegaal, Iris D; Hoogerbrugge, Nicoline; Hoentjen, Frank

2017-03-01

Lynch syndrome and inflammatory bowel diseases (IBD) are associated with an increased risk of colorectal cancer (CRC). However, it is not clear whether the risk of CRC is even higher for patients with a combination of Lynch syndrome and IBD. We investigated the risk for CRC in this subgroup by establishing a Lynch syndrome cohort from the Radboud University Medical Center (Nijmegen, The Netherlands) and the Academic Medical Center (Amsterdam, The Netherlands). Patients with heterozygous germline mutations in MLH1, MSH2 (and EPCAM deletion-mediated MSH2 methylation), MSH6, or PMS2 who were tested and/or treated from 1998 through 2014 were included. Patients who developed IBD were identified by linkage of this cohort to the Dutch nationwide Pathology Registry (PALGA). Subsequently, we compared the risk of CRC between Lynch syndrome patients with IBD and without IBD. Of 1046 patients with Lynch syndrome, 15 developed IBD (1.4%). Patients with Lynch syndrome and IBD were significantly younger (median age, 38.0 y) than patients with Lynch syndrome without IBD (median age, 52.0 y; P = .001). Nevertheless, a similar proportion of patients in each group developed CRC: 4 of the 15 patients (26.7%) with Lynch syndrome and IBD compared with 311 of the 1031 patients (30.2%) with Lynch syndrome without IBD. Patients with Lynch syndrome and IBD developed CRC at a younger age (median age, 36.0 y) than patients with Lynch syndrome without IBD (median age, 46.0 y; P = .045). However, the cumulative incidence of CRC was similar between groups (P = .121). All patients with Lynch syndrome and IBD who developed CRC had ulcerative colitis, producing a higher cumulative incidence of CRC for this IBD subgroup (P Lynch syndrome and IBD develop CRC risk at a younger age than patients without IBD; patients with ulcerative colitis are at especially high risk. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Exploring M33 Through RR Lyrae Stars

OpenAIRE

Pritzl, Barton J.

2013-01-01

Recent surveys have detected RR Lyrae stars in M33, the Triangulum Galaxy. These variable stars are excellent tracers of ancient stellar populations. The RR Lyrae stars have been used to estimate metallicities at various locations within M33, as well as determining the distance to the galaxy. A summary of the M33 RR Lyrae stars is presented here as well as an analysis on what their properties imply for the unique M33 galaxy

A non-randomised controlled trial of the R&R2MHP cognitive skills program in high risk male offenders with severe mental illness.

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C-Y Yip, Vivienne; Gudjonsson, Gisli H; Perkins, Derek; Doidge, Amie; Hopkin, Gareth; Young, Susan

2013-10-18

The growing popularity of offending behavior programs has led to the interest of whether such programs are effective with mentally disordered offenders. This study aimed to evaluate the effectiveness of the Reasoning and Rehabilitation program adapted for offenders with severe mental illness (R&R2 MHP). A sample of 59 adult high risk males detained in a high secure hospital completed questionnaires at baseline and post treatment to assess violent attitudes, anger, coping processes and social problem-solving. An informant measure of social and psychological functioning, including disruptive behavior, was completed by staff at the same time. The data of 30 patients who participated in the group condition were compared using intention to treat analysis with 29 controls who received treatment as usual. 80% of group participants completed the program. In contrast to controls, significant medium-large treatment effects were found at outcome on self-reported measures of violent attitudes, social problem-solving and coping processes. Improvements were endorsed by informant ratings of disruptive behavior, social and psychological functioning. The R&R2MHP had a comparatively low dropout rate and was effective in a sample of high risk mentally disordered offenders requiring detention in high security. Future research should use a randomized controlled design. Current Controlled Trials ACTRN12613000216718.

Eating frequency and risk of colorectal cancer.

Science.gov (United States)

Perrigue, Martine M; Kantor, Elizabeth D; Hastert, Theresa A; Patterson, Ruth; Potter, John D; Neuhouser, Marian L; White, Emily

2013-12-01

Eating frequency is a modifiable aspect of dietary behavior that may affect risk of colorectal cancer (CRC). Although most previous case-control studies indicate a positive association, two prospective studies suggest an inverse association between eating frequency and CRC risk, with evidence of effect modification by diet composition. We examined the association between eating frequency and CRC in a large, prospective cohort study, and explored whether this relationship was modified by sex, coffee consumption, or dietary glycemic load. Between 2000 and 2002, 67,912 western Washington residents aged 50-76 reported average daily meal and snack frequency using a mailed questionnaire as part of the vitamins and lifestyle study. Participants were followed for CRC through linkage with SEER through 2008, over which time 409 CRC cases developed. Hazard Ratios and 95 % Confidence Intervals were obtained using Cox regression. In age- and sex-adjusted models higher (5+ times/d) vs. lower (1-2 times/d) eating frequency was associated with a HR of 0.62 (95 % CI 0.43-0.88, Ptrend = 0.001). However, following further adjustment for BMI, race/ethnicity, alcohol, and other known CRC risk factors, the relationship was no longer statistically significant (HR: 0.76; 95 % CI 0.51, 1.14). No effect modification was observed by sex (Pinteraction = 0.45), coffee consumption (Pinteraction = 0.44), or dietary glycemic load (Pinteraction = 0.90). In subgroup analyses by tumor site, higher vs. lower eating frequency was associated with lower risk for colon (HR 0.65 95 % CI 0.39-1.07, Ptrend = 0.04), but not rectal cancers (HR = 1.08 95 % CI 0.54-2.18, Ptrend = 0.94). The weak inverse association observed between eating frequency and CRC is consistent with findings from other prospective studies. Modification of this relationship by diet quality and participant characteristics should be considered in the future studies.

Adsorção dos corantes RO16, RR2 e RR141 utilizando lodo residual da indústria têxtil Adsorption of dyes RO16, RR2 and RR141 using residual sludge of textile industry

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Andressa Regina Vasques

2011-09-01

Full Text Available A adsorção é uma das técnicas empregadas com sucesso para remoção efetiva da cor presente em efluentes têxteis. Com o objetivo de avaliar os diferentes parâmetros adsortivos, bem como determinar a eficiência de um adsorvente alternativo desenvolvido a partir de lodo residual têxtil na remoção de corantes, foram determinadas curvas de cinética de adsorção e isotermas. Por meio dos dados cinéticos e de equilíbrio obtidos, verificou-se que a 25ºC a adsorção foi favorável para todos os corantes, sendo esta a melhor condição para os corantes RO16 e RR2 na ausência de sais. Para o corante RR141, a adição de NaCl aumentou a capacidade de adsorção do adsorvente no equilíbrio e a adição de Na2SO4 favoreceu a adsorção para o corante RO16, ao contrário do que se observou para os outros dois corantes. A quantidade máxima de corante adsorvida por unidade de massa de adsorvente (q max nas melhores condições adsortivas para os corantes RO16, RR2 e RR141 foi de 81,30, 53,48 e 78,74 mg.g-1, respectivamente.The adsorption is one of the techniques that have been successfully used for effective removal of the dyes present in textile effluents. With the objective to evaluate the different adsorptive parameters, as well as determining the efficiency of one alternative adsorbent in the removal of dyes, kinetics and equilibrium data of adsorption were determined. By the kinetic data and of equilibrium, it was verified that the adsorption was favorable for all the dyes in 25ºC, being the best condition for the dye RO16 and RR2 in the total absence of salt. For the dye RR141, the addition of NaCl increased the adsorption capacity of adsorbent in the equilibrium and the addition of Na2SO4 favored the adsorption for the dye RO16, in contrast to what was observed for the two other dyes. The maximum quantity of dye adsorbed per unit mass of adsorbent (q max in the best adsorptive conditions for the dyes RO16, RR2 and RR141 was of 81

Influence of type 2 diabetes mellitus on Khorana venous thromboembolism risk in colorectal cancer patients

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Ruyao Wang

Full Text Available Background: Many studies have documented the association between venous thromboembolism (VTE and colorectal cancer (CRC. The Khorana model is a VTE risk assessment model for predicting cancer-associated thrombosis. Type 2 diabetes (T2DM has also been reported to increase the risk of VTE. Purpose: The aim of this study was to investigate the influence of T2DM on Khorana VTE risk in CRC patients and to explore the relationship between Khorana VTE category and CRC clinicopathological factors. Methods: This analysis included 615 CRC patients (205 with T2DM. Fibrinogen and D-dimer levels were compared within each group. A comparison was made of the proportion of patients in different Khorana VTE risk categories in CRC patients with and without T2DM. The association between Khorana VTE risk category and clinicopathological factors among all the CRC patients was evaluated. Results: Fibrinogen levels of CRC patients with T2DM were significantly higher than those of non-diabetes patients (4.13 ± 1.06 vs 3.94 ± 0.98, p < 0.001. A higher proportion of CRC patients with T2DM were in the Khorana intermediate-to-high risk category (H = 4.749, p = 0.029. Female sex, diabetes, colon location (compared with rectum, larger tumor size, advanced pT stage and pN stage were correlated with the intermediate-to-high Khorana VTE risk category, with odd ratios (95% confidence intervals [CI] of 1.537 (1.064-2.220, 1.499 (1.027-2.186, 2.313 (1.588-3.370, 2.284 (1.542-3.383, 4.429 (2.088-9.396 and 1.822 (1.230-2.698, respectively. Conclusion: T2DM increases Khorana VTE risk in CRC patients. Female sex, diabetes, colon location, large tumor size and poor stage are associated with the intermediate-to-high Khorana VTE risk category.

Obesity, physical activity and cancer risks: Results from the Cancer, Lifestyle and Evaluation of Risk Study (CLEAR).

Science.gov (United States)

Nunez, Carlos; Bauman, Adrian; Egger, Sam; Sitas, Freddy; Nair-Shalliker, Visalini

2017-04-01

Physical activity (PA) has been associated with lower risk of cardiovascular diseases, but the evidence linking PA with lower cancer risk is inconclusive. We examined the independent and interactive effects of PA and obesity using body mass index (BMI) as a proxy for obesity, on the risk of developing prostate (PC), postmenopausal breast (BC), colorectal (CRC), ovarian (OC) and uterine (UC) cancers. We estimated odds ratios (OR) and 95% confidence intervals (CI), adjusting for cancer specific confounders, in 6831 self-reported cancer cases and 1992 self-reported cancer-free controls from the Cancer Lifestyle and Evaluation of Risk Study, using unconditional logistic regression. For women, BMI was positively associated with UC risk; specifically, obese women (BMI≥30kg/m 2 ) had nearly twice the risk of developing UC compared to women with healthy-BMI-range (risk of developing any cancer type, CRC and PC. In particular, obese men had 37% (OR=1.37;CI:1.11-1.70), 113% (OR=2.13;CI:1.55-2.91) and 51% (OR=1.51;CI:1.17-1.94) higher risks of developing any cancer, CRC and PC respectively, when compared to men with healthy-BMI-range (BMIrisks of CRC, UC and BC. In particular, the highest level of PA (versus nil activity) was associated with reduced risks of CRC (OR=0.60;CI:0.44-0.84) and UC (OR=0.47;CI:0.27-0.80). Reduced risks of BC were associated with low (OR=0.66;CI:0.51-0.86) and moderate (OR=0.72;CI:0.57-0.91) levels of PA. There was no association between PA levels and cancer risks for men. We found no evidence of an interaction between BMI and PA in the CLEAR study. These findings suggest that PA and obesity are independent cancer risk factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Meat intake, cooking methods, dietary carcinogens, and colorectal cancer risk: findings from the Colorectal Cancer Family Registry.

Science.gov (United States)

Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Ulrich, Cornelia M; Potter, John D; Cotterchio, Michelle; Le Marchand, Loic; Stern, Mariana C

2015-06-01

Diets high in red meat and processed meats are established colorectal cancer (CRC) risk factors. However, it is still not well understood what explains this association. We conducted comprehensive analyses of CRC risk and red meat and poultry intakes, taking into account cooking methods, level of doneness, estimated intakes of heterocyclic amines (HCAs) that accumulate during meat cooking, tumor location, and tumor mismatch repair proficiency (MMR) status. We analyzed food frequency and portion size data including a meat cooking module for 3364 CRC cases, 1806 unaffected siblings, 136 unaffected spouses, and 1620 unaffected population-based controls, recruited into the CRC Family Registry. Odds ratios (OR) and 95% confidence intervals (CI) for nutrient density variables were estimated using generalized estimating equations. We found no evidence of an association between total nonprocessed red meat or total processed meat and CRC risk. Our main finding was a positive association with CRC for pan-fried beefsteak (P(trend) carcinogens relevant for CRC risk. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Conditionally reprogrammed cells (CRC) methodology does not allow the in vitro expansion of patient-derived primary and metastatic lung cancer cells.

Science.gov (United States)

Sette, Giovanni; Salvati, Valentina; Giordani, Ilenia; Pilozzi, Emanuela; Quacquarini, Denise; Duranti, Enrico; De Nicola, Francesca; Pallocca, Matteo; Fanciulli, Maurizio; Falchi, Mario; Pallini, Roberto; De Maria, Ruggero; Eramo, Adriana

2018-07-01

Availability of tumor and non-tumor patient-derived models would promote the development of more effective therapeutics for non-small cell lung cancer (NSCLC). Recently, conditionally reprogrammed cells (CRC) methodology demonstrated exceptional potential for the expansion of epithelial cells from patient tissues. However, the possibility to expand patient-derived lung cancer cells using CRC protocols is controversial. Here, we used CRC approach to expand cells from non-tumoral and tumor biopsies of patients with primary or metastatic NSCLC as well as pulmonary metastases of colorectal or breast cancers. CRC cultures were obtained from both tumor and non-malignant tissues with extraordinary high efficiency. Tumor cells were tracked in vitro through tumorigenicity assay, monitoring of tumor-specific genetic alterations and marker expression. Cultures were composed of EpCAM+ lung epithelial cells lacking tumorigenic potential. NSCLC biopsies-derived cultures rapidly lost patient-specific genetic mutations or tumor antigens. Similarly, pulmonary metastases of colon or breast cancer generated CRC cultures of lung epithelial cells. All CRC cultures examined displayed epithelial lung stem cell phenotype and function. In contrast, brain metastatic lung cancer biopsies failed to generate CRC cultures. In conclusion, patient-derived primary and metastatic lung cancer cells were negatively selected under CRC conditions, limiting the expansion to non-malignant lung epithelial stem cells from either tumor or non-tumor tissue sources. Thus, CRC approach cannot be applied for direct therapeutic testing of patient lung tumor cells, as the tumor-derived CRC cultures are composed of (non-tumoral) airway basal cells. © 2018 UICC.

Diagnostic value of fecal tumor M2-pyruvate kinase for CRC screening: a systematic review and meta-analysis.

Science.gov (United States)

Li, Rui; Liu, Jianjun; Xue, Huiping; Huang, Gang

2012-10-15

The measurement of fecal tumor M2-pyruvate kinase (PKM2), overexpressed in tumor cells, has been proposed as a novel tool for detecting colorectal cancer (CRC). However, the sensitivity and specificity of this test varied among studies. The aim of this meta-analysis was to determine the diagnostic accuracy of fecal PKM2 for CRC and to evaluate its utility in the CRC screening. It was compared to guaiac fecal occult blood test (gFOBT) or immunological fecal occult blood test (iFOBT). Through comprehensive literature search, 10 studies met the inclusion criteria and were included. Summary estimates for sensitivity and specificity were calculated by using the bivariate random effect model. The hierarchical summary receiver operating characteristic curve was also undertaken. The overall sensitivity and specificity of fecal PKM2 for detecting CRC were 79% (95% CI = 75-83%) and 81% (95% CI = 73-87%), respectively. The summary positive predictive value and negative predictive value were 74% (95% CI = 56-87%) and 86% (95% CI = 79-91%), respectively. The pooled diagnostic odds ratio was 16 (95% CI = 10-26). In head-to-head comparison, the diagnostic odds ratio of PKM2 and gFOBT for CRC were 10.167 (95% CI = 5.992-17.250) and 6.557 (95% CI = 3.467-12.403), respectively. The diagnostic odds ratio of PKM2 and iFOBT for CRC were 9.542 (95% CI = 5.893-15.452) and 67.248 (95% CI = 16.194-279.26), respectively. The fecal PKM2 test was a diagnostic tool with moderate sensitivity and specificity for detecting CRC. Its diagnostic efficiency was similar to that of gFOBT. Because of its relatively low specificity and positive predict value, fecal PKM2 was not recommended used alone as a screening tool for CRC. Copyright © 2012 UICC.

Co-expression analysis identifies CRC and AP1 the regulator of Arabidopsis fatty acid biosynthesis.

Science.gov (United States)

Han, Xinxin; Yin, Linlin; Xue, Hongwei

2012-07-01

Fatty acids (FAs) play crucial rules in signal transduction and plant development, however, the regulation of FA metabolism is still poorly understood. To study the relevant regulatory network, fifty-eight FA biosynthesis genes including de novo synthases, desaturases and elongases were selected as "guide genes" to construct the co-expression network. Calculation of the correlation between all Arabidopsis thaliana (L.) genes with each guide gene by Arabidopsis co-expression dating mining tools (ACT) identifies 797 candidate FA-correlated genes. Gene ontology (GO) analysis of these co-expressed genes showed they are tightly correlated to photosynthesis and carbohydrate metabolism, and function in many processes. Interestingly, 63 transcription factors (TFs) were identified as candidate FA biosynthesis regulators and 8 TF families are enriched. Two TF genes, CRC and AP1, both correlating with 8 FA guide genes, were further characterized. Analyses of the ap1 and crc mutant showed the altered total FA composition of mature seeds. The contents of palmitoleic acid, stearic acid, arachidic acid and eicosadienoic acid are decreased, whereas that of oleic acid is increased in ap1 and crc seeds, which is consistent with the qRT-PCR analysis revealing the suppressed expression of the corresponding guide genes. In addition, yeast one-hybrid analysis and electrophoretic mobility shift assay (EMSA) revealed that CRC can bind to the promoter regions of KCS7 and KCS15, indicating that CRC may directly regulate FA biosynthesis. © 2012 Institute of Botany, Chinese Academy of Sciences.

Risk of colorectal cancer among immigrants to Ontario, Canada.

Science.gov (United States)

Paszat, Lawrence; Sutradhar, Rinku; Liu, Ying; Baxter, Nancy N; Tinmouth, Jill; Rabeneck, Linda

2017-07-06

The risk of colorectal cancer (CRC) varies around the world and between females and males. We aimed to compare the risk of CRC among immigrants to Ontario, Canada, to its general population. We used an exposure-control matched design. We identified persons in the Immigration, Refugees and Citizenship Canada Permanent Resident Database with first eligibility for the Ontario Health Insurance Plan between July 1, 1991 and June 30, 2008 at age 40 years or older, and matched five controls by year of birth and sex on the immigrant's first eligibility date. We identified CRC from the Ontario Cancer Registry between the index date and December 31, 2014. All analyses were stratified by sex. We calculated crude and relative rates of CRC. We estimated risk of CRC over time by the Kaplan-Meier method and compared immigrants to controls in age and sex stratified strata using log-rank tests. We modeled the hazard of CRC using Cox proportional hazards regression, accounting for within-cluster correlation by a robust sandwich variance estimation approach, and assessed an interaction with time since eligibility. Among females, 1877 cases of CRC were observed among 209,843 immigrants, and 16,517 cases among 1,049,215 controls; the crude relative rate among female immigrants was 0.623. Among males, 1956 cases of CRC were observed among 191,792 immigrants and 18,329 cases among 958,960 controls; the crude relative rate among male immigrants was 0.582.. Comparing immigrants to controls in all age and sex stratified strata, the log rank test p  = 75 years at index, where p = 0.01. The age-adjusted hazard ratio (HR) for CRC among female immigrants was 0.63 (95% CI 0.59, 0.67) during the first 10 years, and 0.66 (95% CI 0.59, 0.74) thereafter. Among male immigrants the age-adjusted HR = 0.55 (95% CI 0.52, 0.59) during the first 10 years and increased to 0.63 (95% CI 0.57, 0.71) thereafter. The adjusted HR > = 1 only among immigrants born in Europe and Central Asia. The risk

Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC.

Science.gov (United States)

Scarpa, Marco; Scarpa, Melania; Castagliuolo, Ignazio; Erroi, Francesca; Kotsafti, Andromachi; Basato, Silvia; Brun, Paola; D'Incà, Renata; Rugge, Massimo; Angriman, Imerio; Castoro, Carlo

2016-03-01

BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC. The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC. Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance.

Risk factors for colorectal cancer in patients with multiple serrated polyps: a cross-sectional case series from genetics clinics.

Directory of Open Access Journals (Sweden)

Daniel D Buchanan

2010-07-01

Full Text Available Patients with multiple serrated polyps are at an increased risk for developing colorectal cancer (CRC. Recent reports have linked cigarette smoking with the subset of CRC that develops from serrated polyps. The aim of this work therefore was to investigate the association between smoking and the risk of CRC in high-risk genetics clinic patients presenting with multiple serrated polyps.We identified 151 Caucasian individuals with multiple serrated polyps including at least 5 outside the rectum, and classified patients into non-smokers, current or former smokers at the time of initial diagnosis of polyposis. Cases were individuals with multiple serrated polyps who presented with CRC. Controls were individuals with multiple serrated polyps and no CRC. Multivariate logistic regression was performed to estimate associations between smoking and CRC with adjustment for age at first presentation, sex and co-existing traditional adenomas, a feature that has been consistently linked with CRC risk in patients with multiple serrated polyps. CRC was present in 56 (37% individuals at presentation. Patients with at least one adenoma were 4 times more likely to present with CRC compared with patients without adenomas (OR = 4.09; 95%CI 1.27 to 13.14; P = 0.02. For females, the odds of CRC decreased by 90% in current smokers as compared to never smokers (OR = 0.10; 95%CI 0.02 to 0.47; P = 0.004 after adjusting for age and adenomas. For males, there was no relationship between current smoking and CRC. There was no statistical evidence of an association between former smoking and CRC for both sexes.A decreased odds for CRC was identified in females with multiple serrated polyps who currently smoke, independent of age and the presence of a traditional adenoma. Investigations into the biological basis for these observations could lead to non-smoking-related therapies being developed to decrease the risk of CRC and colectomy in these patients.

Lifestyle Changes and the Risk of Colorectal Cancer among ...

African Journals Online (AJOL)

Colorectal cancer (CRC) is a public health challenge in developed countries and ... of this cancer in sub-Saharan Africa, Middle East, South Asia and the Caribbean. ... populations from low risk regions to countries in North America, Europe and ... risk of colorectal cancer (CRC) in their newly found environment as a result of ...

Computational prediction of the Crc regulon identifies genus-wide and species-specific targets of catabolite repression control in Pseudomonas bacteria

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O'Gara Fergal

2010-11-01

Full Text Available Abstract Background Catabolite repression control (CRC is an important global control system in Pseudomonas that fine tunes metabolism in order optimise growth and metabolism in a range of different environments. The mechanism of CRC in Pseudomonas spp. centres on the binding of a protein, Crc, to an A-rich motif on the 5' end of an mRNA resulting in translational down-regulation of target genes. Despite the identification of several Crc targets in Pseudomonas spp. the Crc regulon has remained largely unexplored. Results In order to predict direct targets of Crc, we used a bioinformatics approach based on detection of A-rich motifs near the initiation of translation of all protein-encoding genes in twelve fully sequenced Pseudomonas genomes. As expected, our data predict that genes related to the utilisation of less preferred nutrients, such as some carbohydrates, nitrogen sources and aromatic carbon compounds are targets of Crc. A general trend in this analysis is that the regulation of transporters is conserved across species whereas regulation of specific enzymatic steps or transcriptional activators are often conserved only within a species. Interestingly, some nucleoid associated proteins (NAPs such as HU and IHF are predicted to be regulated by Crc. This finding indicates a possible role of Crc in indirect control over a subset of genes that depend on the DNA bending properties of NAPs for expression or repression. Finally, some virulence traits such as alginate and rhamnolipid production also appear to be regulated by Crc, which links nutritional status cues with the regulation of virulence traits. Conclusions Catabolite repression control regulates a broad spectrum of genes in Pseudomonas. Some targets are genus-wide and are typically related to central metabolism, whereas other targets are species-specific, or even unique to particular strains. Further study of these novel targets will enhance our understanding of how Pseudomonas

Computational prediction of the Crc regulon identifies genus-wide and species-specific targets of catabolite repression control in Pseudomonas bacteria.

Science.gov (United States)

Browne, Patrick; Barret, Matthieu; O'Gara, Fergal; Morrissey, John P

2010-11-25

Catabolite repression control (CRC) is an important global control system in Pseudomonas that fine tunes metabolism in order optimise growth and metabolism in a range of different environments. The mechanism of CRC in Pseudomonas spp. centres on the binding of a protein, Crc, to an A-rich motif on the 5' end of an mRNA resulting in translational down-regulation of target genes. Despite the identification of several Crc targets in Pseudomonas spp. the Crc regulon has remained largely unexplored. In order to predict direct targets of Crc, we used a bioinformatics approach based on detection of A-rich motifs near the initiation of translation of all protein-encoding genes in twelve fully sequenced Pseudomonas genomes. As expected, our data predict that genes related to the utilisation of less preferred nutrients, such as some carbohydrates, nitrogen sources and aromatic carbon compounds are targets of Crc. A general trend in this analysis is that the regulation of transporters is conserved across species whereas regulation of specific enzymatic steps or transcriptional activators are often conserved only within a species. Interestingly, some nucleoid associated proteins (NAPs) such as HU and IHF are predicted to be regulated by Crc. This finding indicates a possible role of Crc in indirect control over a subset of genes that depend on the DNA bending properties of NAPs for expression or repression. Finally, some virulence traits such as alginate and rhamnolipid production also appear to be regulated by Crc, which links nutritional status cues with the regulation of virulence traits. Catabolite repression control regulates a broad spectrum of genes in Pseudomonas. Some targets are genus-wide and are typically related to central metabolism, whereas other targets are species-specific, or even unique to particular strains. Further study of these novel targets will enhance our understanding of how Pseudomonas bacteria integrate nutritional status cues with the regulation

Computational prediction of the Crc regulon identifies genus-wide and species-specific targets of catabolite repression control in Pseudomonas bacteria

LENUS (Irish Health Repository)

Browne, Patrick

2010-11-25

Abstract Background Catabolite repression control (CRC) is an important global control system in Pseudomonas that fine tunes metabolism in order optimise growth and metabolism in a range of different environments. The mechanism of CRC in Pseudomonas spp. centres on the binding of a protein, Crc, to an A-rich motif on the 5\\' end of an mRNA resulting in translational down-regulation of target genes. Despite the identification of several Crc targets in Pseudomonas spp. the Crc regulon has remained largely unexplored. Results In order to predict direct targets of Crc, we used a bioinformatics approach based on detection of A-rich motifs near the initiation of translation of all protein-encoding genes in twelve fully sequenced Pseudomonas genomes. As expected, our data predict that genes related to the utilisation of less preferred nutrients, such as some carbohydrates, nitrogen sources and aromatic carbon compounds are targets of Crc. A general trend in this analysis is that the regulation of transporters is conserved across species whereas regulation of specific enzymatic steps or transcriptional activators are often conserved only within a species. Interestingly, some nucleoid associated proteins (NAPs) such as HU and IHF are predicted to be regulated by Crc. This finding indicates a possible role of Crc in indirect control over a subset of genes that depend on the DNA bending properties of NAPs for expression or repression. Finally, some virulence traits such as alginate and rhamnolipid production also appear to be regulated by Crc, which links nutritional status cues with the regulation of virulence traits. Conclusions Catabolite repression control regulates a broad spectrum of genes in Pseudomonas. Some targets are genus-wide and are typically related to central metabolism, whereas other targets are species-specific, or even unique to particular strains. Further study of these novel targets will enhance our understanding of how Pseudomonas bacteria integrate

Aberrant methylation of GCNT2 is tightly related to lymph node metastasis of primary CRC.

Science.gov (United States)

Nakamura, Kazunori; Yamashita, Keishi; Sawaki, Hiromichi; Waraya, Mina; Katoh, Hiroshi; Nakayama, Nobukazu; Kawamata, Hiroshi; Nishimiya, Hiroshi; Ema, Akira; Narimatsu, Hisashi; Watanabe, Masahiko

2015-03-01

Glycoprotein expression profile is dramatically altered in human cancers; however, specific glycogenes have not been fully identified. A comprehensive real-time polymerase chain reaction (PCR) system for glycogenes (CRPS-G) identified several outstanding glycogenes. GCNT2 was of particular interest after GCNT2 expression and epigenetics were rigorously investigated in primary colorectal cancer (CRC). The highlights of this work can be summarized as follows: (i) Expression of GCNT2 was remarkably suppressed. (ii) Silenced expression of GCNT2 was reactivated by combined demethylating agents. (iii) Promoter DNA methylation of GCNT2 was silenced in CRC cell lines and tissues. Hypomethylation of GCNT2 variant 2 is tightly associated with lymph node metastasis in primary CRC. (iv) GCNT2 methylation level in the normal tissues also showed a close association with that in the tumor tissues and reflected lymph node metastasis. We identified aberrant expression of GCNT2, which can be explained by promoter DNA hypermethylation. Hypomethylation of the GCNT2 variant 2 reflected lymph node metastasis of CRC in the tumor and normal tissues. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

NARCIS (Netherlands)

Eggermond, A.M. van; Schaapveld, M.; Janus, C.P.; Boer, J.P. de; Krol, A.D.; Zijlstra, J.M.; Maazen, R.W.M. van der; Kremer, L.C.; Leerdam, M.E. van; Louwman, M.W.; Visser, O; Bruin, M.L. De; Aleman, B.M.; Leeuwen, F.E. van

2017-01-01

BACKGROUND: Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens. METHODS: In a

Polymorphisms in NFkB, PXR, LXR and risk of colorectal cancer in a prospective study of Danes

International Nuclear Information System (INIS)

Andersen, Vibeke; Christensen, Jane; Overvad, Kim; Tjønneland, Anne; Vogel, Ulla

2010-01-01

Transcription factors and nuclear receptors constitute a link between exposure to heterocyclic amines and polycyclic aromatic hydrocarbons from meat and tobacco smoke and colorectal cancer (CRC) risk. The aim of this study was to investigate if polymorphisms in nuclear factor kappa-B, pregnane X receptor, and liver X receptor were associated with risk of CRC, and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. The polymorphisms nuclear factor kappa-B (NFkB, NFKB1) -94 insertion/deletion ATTG (rs28362491), pregnane X receptor (PXR, NR1I2) A-24381C (rs1523127), C8055T (rs2276707), A7635G (rs6785049), liver X receptor (LXR-β, NR1H3) C-rs1405655T, T-rs2695121C were assessed together with lifestyle factors in a nested case-cohort study of 378 CRC cases and 756 random participants from the Danish prospective Diet, Cancer and Health study of 57,053 persons. Carriers of NFkB -94deletion were at 1.45-fold higher risk of CRC than homozygous carriers of the insertion allele (incidence rate ratio (IRR) = 1.45, 95% confidence interval (95% CI): 1.10-1.92). There was interaction between this polymorphism and intake of red and processed meat in relation to CRC risk. Carriers of NFkB -94deletion were at 3% increased risk pr 25 gram meat per day (95% CI: 0.98-1.09) whereas homozygous carriers of the insertion were not at increased risk (p for interaction = 0.03). PXR and LXR polymorphisms were not associated with CRC risk. There was no interaction between use of nonsteroid antiinflammatory drugs (NSAID) or smoking status and NFkB, PXR or LXR polymorphisms. A polymorphism in NFkB was associated with CRC risk and there was interaction between this polymorphism and meat intake in relation to CRC risk. This study suggests a role for NFkB in CRC aetiology

Polymorphisms in NFkB, PXR, LXR and risk of colorectal cancer in a prospective study of Danes

Directory of Open Access Journals (Sweden)

Andersen Vibeke

2010-09-01

Full Text Available Abstract Background Transcription factors and nuclear receptors constitute a link between exposure to heterocyclic amines and polycyclic aromatic hydrocarbons from meat and tobacco smoke and colorectal cancer (CRC risk. The aim of this study was to investigate if polymorphisms in nuclear factor kappa-B, pregnane X receptor, and liver X receptor were associated with risk of CRC, and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. Methods The polymorphisms nuclear factor kappa-B (NFkB, NFKB1 -94 insertion/deletion ATTG (rs28362491, pregnane X receptor (PXR, NR1I2 A-24381C (rs1523127, C8055T (rs2276707, A7635G (rs6785049, liver X receptor (LXR-β, NR1H3 C-rs1405655T, T-rs2695121C were assessed together with lifestyle factors in a nested case-cohort study of 378 CRC cases and 756 random participants from the Danish prospective Diet, Cancer and Health study of 57,053 persons. Results Carriers of NFkB -94deletion were at 1.45-fold higher risk of CRC than homozygous carriers of the insertion allele (incidence rate ratio (IRR = 1.45, 95% confidence interval (95% CI: 1.10-1.92. There was interaction between this polymorphism and intake of red and processed meat in relation to CRC risk. Carriers of NFkB -94deletion were at 3% increased risk pr 25 gram meat per day (95% CI: 0.98-1.09 whereas homozygous carriers of the insertion were not at increased risk (p for interaction = 0.03. PXR and LXR polymorphisms were not associated with CRC risk. There was no interaction between use of nonsteroid antiinflammatory drugs (NSAID or smoking status and NFkB, PXR or LXR polymorphisms. Conclusions A polymorphism in NFkB was associated with CRC risk and there was interaction between this polymorphism and meat intake in relation to CRC risk. This study suggests a role for NFkB in CRC aetiology.

The Crc and Hfq proteins of Pseudomonas putida cooperate in catabolite repression and formation of ribonucleic acid complexes with specific target motifs.

Science.gov (United States)

Moreno, Renata; Hernández-Arranz, Sofía; La Rosa, Ruggero; Yuste, Luis; Madhushani, Anjana; Shingler, Victoria; Rojo, Fernando

2015-01-01

The Crc protein is a global regulator that has a key role in catabolite repression and optimization of metabolism in Pseudomonads. Crc inhibits gene expression post-transcriptionally, preventing translation of mRNAs bearing an AAnAAnAA motif [the catabolite activity (CA) motif] close to the translation start site. Although Crc was initially believed to bind RNA by itself, this idea was recently challenged by results suggesting that a protein co-purifying with Crc, presumably the Hfq protein, could account for the detected RNA-binding activity. Hfq is an abundant protein that has a central role in post-transcriptional gene regulation. Herein, we show that the Pseudomonas putida Hfq protein can recognize the CA motifs of RNAs through its distal face and that Crc facilitates formation of a more stable complex at these targets. Crc was unable to bind RNA in the absence of Hfq. However, pull-down assays showed that Crc and Hfq can form a co-complex with RNA containing a CA motif in vitro. Inactivation of the hfq or the crc gene impaired catabolite repression to a similar extent. We propose that Crc and Hfq cooperate in catabolite repression, probably through forming a stable co-complex with RNAs containing CA motifs to result in inhibition of translation initiation. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

Whole Gene Capture Analysis of 15 CRC Susceptibility Genes in Suspected Lynch Syndrome Patients.

Science.gov (United States)

Jansen, Anne M L; Geilenkirchen, Marije A; van Wezel, Tom; Jagmohan-Changur, Shantie C; Ruano, Dina; van der Klift, Heleen M; van den Akker, Brendy E W M; Laros, Jeroen F J; van Galen, Michiel; Wagner, Anja; Letteboer, Tom G W; Gómez-García, Encarna B; Tops, Carli M J; Vasen, Hans F; Devilee, Peter; Hes, Frederik J; Morreau, Hans; Wijnen, Juul T

2016-01-01

Lynch Syndrome (LS) is caused by pathogenic germline variants in one of the mismatch repair (MMR) genes. However, up to 60% of MMR-deficient colorectal cancer cases are categorized as suspected Lynch Syndrome (sLS) because no pathogenic MMR germline variant can be identified, which leads to difficulties in clinical management. We therefore analyzed the genomic regions of 15 CRC susceptibility genes in leukocyte DNA of 34 unrelated sLS patients and 11 patients with MLH1 hypermethylated tumors with a clear family history. Using targeted next-generation sequencing, we analyzed the entire non-repetitive genomic sequence, including intronic and regulatory sequences, of 15 CRC susceptibility genes. In addition, tumor DNA from 28 sLS patients was analyzed for somatic MMR variants. Of 1979 germline variants found in the leukocyte DNA of 34 sLS patients, one was a pathogenic variant (MLH1 c.1667+1delG). Leukocyte DNA of 11 patients with MLH1 hypermethylated tumors was negative for pathogenic germline variants in the tested CRC susceptibility genes and for germline MLH1 hypermethylation. Somatic DNA analysis of 28 sLS tumors identified eight (29%) cases with two pathogenic somatic variants, one with a VUS predicted to pathogenic and LOH, and nine cases (32%) with one pathogenic somatic variant (n = 8) or one VUS predicted to be pathogenic (n = 1). This is the first study in sLS patients to include the entire genomic sequence of CRC susceptibility genes. An underlying somatic or germline MMR gene defect was identified in ten of 34 sLS patients (29%). In the remaining sLS patients, the underlying genetic defect explaining the MMRdeficiency in their tumors might be found outside the genomic regions harboring the MMR and other known CRC susceptibility genes.

Quantitative proteomics unravels that the post-transcriptional regulator Crc modulates the generation of vesicles and secreted virulence determinants of Pseudomonas aeruginosa.

Science.gov (United States)

Reales-Calderón, Jose Antonio; Corona, Fernando; Monteoliva, Lucía; Gil, Concha; Martínez, Jose Luis

2015-09-08

Recent research indicates that the post-transcriptional regulator Crc modulates susceptibility to antibiotics and virulence in Pseudomonas aeruginosa. Several P. aeruginosa virulence factors are secreted or engulfed in vesicles. To decipher the Crc modulation of P. aeruginosa virulence, we constructed a crc deficient mutant and measure the proteome associated extracellular vesicles and the vesicle-free secretome using iTRAQ. Fifty vesicle-associated proteins were more abundant and 14 less abundant in the crc-defective strain, whereas 37 were more abundant and 17 less abundant in the vesicle-free secretome. Among them, virulence determinants, such as ToxA, protease IV, azurin, chitin-binding protein, PlcB and Hcp1, were less abundant in the crc-defective mutant. Transcriptomic analysis revealed that some of the observed changes were post-transcriptional and, thus, could be attributed to a direct Crc regulatory role; whereas, for other differentially secreted proteins, the regulatory role was likely indirect. We also observed that the crc mutant presented an impaired vesicle-associated secretion of quorum sensing signal molecules and less cytotoxicity than its wild-type strain. Our results offer new insights into the mechanisms by which Crc regulates P. aeruginosa virulence, through the modulation of vesicle formation and secretion of both virulence determinants and quorum sensing signals. This article is part of a Special Issue entitled: HUPO 2014. Published by Elsevier B.V.

G9a stimulates CRC growth by inducing p53 Lys373 dimethylation-dependent activation of Plk1.

Science.gov (United States)

Zhang, Jie; Wang, Yafang; Shen, Yanyan; He, Pengxing; Ding, Jian; Chen, Yi

2018-01-01

Rationale: G9a is genetically deregulated in various tumor types and is important for cell proliferation; however, the mechanism underlying G9a-induced carcinogenesis, especially in colorectal cancer (CRC), is unclear. Here, we investigated if G9a exerts oncogenic effects in CRC by increasing polo-like kinase 1 (Plk1) expression. Thus, we further characterized the detailed molecular mechanisms. Methods: The role of Plk1 in G9a aberrant CRC was determined by performing different in vitro and in vivo assays, including assessment of cell growth by performing cell viability assay and assessment of signaling transduction profiles by performing immunoblotting, in the cases of pharmacological inhibition or short RNA interference-mediated suppression of G9a. Detailed molecular mechanisms underlying the effect of G9a on Plk1 expression were determined by performing point mutation analysis, chromatin immunoprecipitation analysis, and luciferase reporter assay. Correlation between G9a and Plk1 expression was determined by analyzing clinical samples of patients with CRC by performing immunohistochemistry. Results: Our study is the first to report a significant positive correlation between G9a and Plk1 levels in 89 clinical samples of patients with CRC. Moreover, G9a depletion decreased Plk1 expression and suppressed CRC cell growth both in vitro and in vivo , thus confirming the significant correlation between G9a and Plk1 levels. Further, we observed that G9a-induced Plk1 regulation depended on p53 inhibition. G9a dimethylated p53 at lysine 373, which in turn increased Plk1 expression and promoted CRC cell growth. Conclusions: These results indicate that G9a-induced and p53-dependent epigenetic programing stimulates the growth of colon cancer, which also suggests that G9a inhibitors that restore p53 activity are promising therapeutic agents for treating colon cancer, especially for CRC expressing wild-type p53.

Meat intake, cooking methods, dietary carcinogens, and colorectal cancer risk: findings from the Colorectal Cancer Family Registry

International Nuclear Information System (INIS)

Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Ulrich, Cornelia M; Potter, John D; Cotterchio, Michelle; Le Marchand, Loic; Stern, Mariana C

2015-01-01

Diets high in red meat and processed meats are established colorectal cancer (CRC) risk factors. However, it is still not well understood what explains this association. We conducted comprehensive analyses of CRC risk and red meat and poultry intakes, taking into account cooking methods, level of doneness, estimated intakes of heterocyclic amines (HCAs) that accumulate during meat cooking, tumor location, and tumor mismatch repair proficiency (MMR) status. We analyzed food frequency and portion size data including a meat cooking module for 3364 CRC cases, 1806 unaffected siblings, 136 unaffected spouses, and 1620 unaffected population-based controls, recruited into the CRC Family Registry. Odds ratios (OR) and 95% confidence intervals (CI) for nutrient density variables were estimated using generalized estimating equations. We found no evidence of an association between total nonprocessed red meat or total processed meat and CRC risk. Our main finding was a positive association with CRC for pan-fried beefsteak (P trend < 0.001), which was stronger among MMR deficient cases (heterogeneity P = 0.059). Other worth noting associations, of borderline statistical significance after multiple testing correction, were a positive association between diets high in oven-broiled short ribs or spareribs and CRC risk (P trend = 0.002), which was also stronger among MMR-deficient cases, and an inverse association with grilled hamburgers (P trend = 0.002). Our results support the role of specific meat types and cooking practices as possible sources of human carcinogens relevant for CRC risk

Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

NARCIS (Netherlands)

van Eggermond, Anna M.; Schaapveld, Michael; Janus, Cécile Pm; de Boer, Jan Paul; Krol, Augustinus Dg; Zijlstra, Josée M.; van der Maazen, Richard Wm; Kremer, Leontien C.; van Leerdam, Monique E.; Louwman, Marieke Wj; Visser, Otto; de Bruin, Marie L.; Aleman, Berthe Mp; van Leeuwen, Flora E.

2017-01-01

Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens. In a Dutch cohort of 3121

A DASH dietary pattern and the risk of colorectal cancer in Canadian adults.

Science.gov (United States)

Jones-McLean, E; Hu, J; Greene-Finestone, L S; de Groh, M

2015-03-01

Colorectal cancer (CRC) is a high incidence cancer affecting many Canadian adults each year. Diet is important in the etiology of CRC with many dietary components identified as potential risk factors. The Dietary Approaches to Stop Hypertension (DASH) diet is a well-established pattern to characterize overall eating. The purpose of this study was to characterize a DASH pattern within the Canadian context and to assess its relationship to the risk of CRC in Canadian adults. Unconditional multiple logistic regression with control for confounding variables was performed using data from the National Enhanced Cancer Surveillance Study. Dietary intake was captured for this case-control study through a food frequency questionnaire (FFQ) and categorized into a DASH score ranging from 0 to 10 representing a poor to a strong DASH pattern respectively. Consuming a strong DASH pattern of eating (score ≥ 8) was not common in the 3161 cases and 3097 controls. Overall, only 10.8% of men and 13.6% of women had a strong DASH pattern. Multivariate analysis demonstrated a trend for decreasing risk of CRC in men with increasing DASH scores (p value for trend = .007). Men with a strong DASH score had a 33% reduction in risk of CRC compared to those with a low DASH score. There were no significant trends for women for CRC or for colon or rectal cancers separately. Our findings are similar to other researchers suggesting a benefit with a strong DASH pattern associated with a decreased risk of CRC, especially in men. Research should further investigate our gender-based differences.

Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk

DEFF Research Database (Denmark)

Hoeft, B.; Linseisen, J.; Beckmann, L.

2010-01-01

as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. Three hundred......Colorectal cancer (CRC) is the third most common malignant tumor and the fourth leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in-depth analysis of inter-individual differences in fatty acid metabolizing genes...... variants with CRC risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and CRC risk....

Joint effects of colorectal cancer susceptibility loci, circulating 25-hydroxyvitamin D and risk of colorectal cancer.

Directory of Open Access Journals (Sweden)

Linda T Hiraki

Full Text Available Genome wide association studies (GWAS have identified several SNPs associated with colorectal cancer (CRC susceptibility. Vitamin D is also inversely associated with CRC risk.We examined main and joint effects of previously GWAS identified genetic markers of CRC and plasma 25-hydroxyvitamin D (25(OHD on CRC risk in three prospective cohorts: the Nurses' Health Study (NHS, the Health Professionals Follow-up Study (HPFS, and the Physicians' Health Study (PHS. We included 1895 CRC cases and 2806 controls with genomic DNA. We calculated odds ratios and 95% confidence intervals for CRC associated with additive genetic risk scores (GRSs comprised of all CRC SNPs and subsets of these SNPs based on proximity to regions of increased vitamin D receptor binding to vitamin D response elements (VDREs, based on published ChiP-seq data. Among a subset of subjects with additional prediagnostic 25(OHD we tested multiplicative interactions between plasma 25(OHD and GRS's. We used fixed effects models to meta-analyze the three cohorts.The per allele multivariate OR was 1.12 (95% CI, 1.06-1.19 for GRS-proximalVDRE; and 1.10 (95% CI, 1.06-1.14 for GRS-nonproxVDRE. The lowest quartile of plasma 25(OHD compared with the highest, had a multivariate OR of 0.63 (95% CI, 0.48-0.82 for CRC. We did not observe any significant interactions between any GRSs and plasma 25(OHD.We did not observe evidence for the modification of genetic susceptibility for CRC according to vitamin D status, or evidence that the effect of common CRC risk alleles differed according to their proximity to putative VDR binding sites.

Variation in the vitamin D receptor gene is not associated with risk of colorectal cancer in the Czech Republic.

LENUS (Irish Health Repository)

Hughes, David J

2012-02-01

PURPOSE: Increased levels of vitamin D may protect against colorectal cancer (CRC) development and recurrence. Accumulating epidemiologic evidence suggests these effects may be partly mediated by genetic variants of the vitamin D receptor (VDR) proposed to be associated with altered risk of CRC. We wished to determine if common VDR polymorphisms affected CRC risk in the Czech Republic, a homogenous European population with a high CRC incidence rate. METHODS: Frequencies of the common VDR gene polymorphisms rs2238136, rs1544410 (BsmI), rs7975232 (ApaI), and rs731236 (TaqI) were determined using allele-specific PCR in a case control analysis of a series of 754 CRC patients and 627 patients without malignant disease recruited from centers throughout the Czech Republic. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals for the association between these variants and risk of CRC. RESULTS: None of the four polymorphisms tested had any significant effect on CRC risk. No significant differences were observed in susceptibility when the population was stratified by anatomical sub-site, sex, BMI, smoking, alcohol, or presence of polyps. CONCLUSIONS: We conclude that common variation in the VDR gene had little effect on its own on predisposition to sporadic CRC in the Czech population.

Food groups and the risk of colorectal cancer: results from a Jordanian case-control study.

Science.gov (United States)

Abu Mweis, Suhad S; Tayyem, Reema F; Shehadah, Ihab; Bawadi, Hiba A; Agraib, Lana M; Bani-Hani, Kamal E; Al-Jaberi, Tareq; Al-Nusairr, Majed

2015-07-01

The role of diet in colorectal cancer (CRC) in Jordan has not been studied previously. This study aimed at examining the association between food groups (including grains, fruits, vegetables, milk, and meat and legumes) and CRC risk in Jordan. We compared intakes of the different food groups among CRC patients (n=167) and matched controls (n=240) by age, sex, occupation, and marital status. A validated food frequency questionnaire was used to collect dietary data. Logistic regression was used to evaluate the association of quartiles of intakes of the different food groups with CRC risk. In addition, the association of selected food items with CRC risk was examined. Odds ratios (ORs) for the fourth versus the first quartile of intake were 2.92 [95% confidence interval (CI): 1.40-6.08] for grains, 1.66 (95% CI: 0.81-3.40) for vegetables, 0.55 (95% CI: 0.26-1.16) for fruits, 0.96 (95% CI: 0.46-1.97) for milk, and 1.43 (95% CI: 0.68-2.98) for meat and legumes. In a comparison of the highest with the lowest weekly frequency of consumption, there was a direct association between the risk of CRC and the frequency of consumption of chicken (OR=2.52, 95% CI: 1.33-4.77). An increase in risk was observed with increased consumption of white bread (OR=3.13, 95% CI: 1.18-9.25), whereas consumption of whole bread was associated with a decreased risk for CRC (OR=0.32, 95% CI: 0.12-0.84). Our results support a role of diet in CRC. Direct associations were found for grains, white bread, and chicken, whereas an inverse relation was reported for whole bread.

Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC)

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Winther, Stine Braendegaard; Zubcevic, Kanita; Qvortrup, Camilla

2016-01-01

BACKGROUND: An aging population will increase the number of older patients with metastatic colorectal cancer (mCRC). However, there is limited knowledge about treatment in older patients as they are under-represented in clinical trials. The oral fluoropyrimidine S-1 is associated with a lower rate...... of adverse events than capecitabine and may therefore be a suitable drug for elderly. However, data on the use of S-1 in Caucasian mCRC patients are lacking/scarce. MATERIAL AND METHODS: In the present study we evaluated safety and the efficacy of S-1 alone or in combination with oxaliplatin (SOx......) or irinotecan (IRIS) in older mCRC patients. Patients who received at least one cycle of S-1 (first-line therapy), SOx (mainly first-line therapy) or IRIS (second-line therapy) were included. RESULTS: From June 2012 to December 2014, 71 older patients received ≥1 cycle of either S-1 (n = 9), SOx (n = 44...

Atrophic Gastritis and the Risk of Incident Colorectal Cancer

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Laiyemo, Adeyinka O.; Kamangar, Farin; Marcus, Pamela M.; Taylor, Philip R.; Virtamo, Jarmo; Albanes, Demetrius; Stolzenberg-Solomon, Rachael Z.

2012-01-01

Objective Previous studies evaluating whether risk factors for gastric cancer are also associated with colorectal cancer (CRC) have shown inconsistent results. We prospectively examined the association of atrophic gastritis, a pre-malignant condition for gastric cancer and long-term sequelae common to many exposure factors, and the risk of incident CRC. Methods A total of 20,928 Finnish male smokers, aged 50–69, who were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) had serum pepsinogen I (SPGI) levels measured. Participants with low SPGI levels (gastritis was histologically confirmed in 1,006 (95.0%) participants. We used Cox proportional hazards regression to evaluate the risk of incident CRC. Results During a mean follow-up of 11.3 years (236,258 person-years), 425 incident CRC were diagnosed. The incidence rates were 1.82, 1.48, and 1.82 per 1,000 person-years of follow-up for participants with normal SPGI (≥25 µg/l), low SPGI, and histologically-confirmed atrophic gastritis, respectively. Compared to subjects with normal SPGI, there was no increased risk of CRC among subjects with low SPGI (Adjusted Hazard Ratio (HR) = 0.71; 95%CI: 0.47–1.05) and among those with histologically-confirmed atrophic gastritis (Adjusted HR = 0.86; 95%CI: 0.55–1.34). Conclusions Atrophic gastritis is not associated with an increased risk of colorectal cancer among male smokers. PMID:19838812

Red wine consumption not associated with reduced risk of colorectal cancer.

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Chao, Chun; Haque, Reina; Caan, Bette J; Poon, Kwun-Yee T; Tseng, Hung-Fu; Quinn, Virginia P

2010-01-01

Red wine contains polyphenol antioxidants that inhibit colorectal cancer (CRC) development in animal studies. We investigated the effect of red wine intake on risk of CRC in the California Men's Health Study (CMHS). CMHS is a prospective, multiethnic cohort of middle-aged men who were members of the Kaiser Permanente (KP) California Health Plans and completed study questionnaires between 2002-2003. Incident CRC were identified from the health plan cancer registries through the end of 2007 (n = 287). To properly account for potential confounding by previous endoscopy screening, we restricted the primary analyses to CMHS men continuously enrolled in KP between 1998-2002 (n = 43,483 and CRC = 176). We used multivariable Cox regression to adjust for important confounders. We did not find an inverse association between moderate red wine intake and risk of CRC. The hazard ratio for consuming >/=1 drink/day (average = 2 drinks/day) was 1.16, 95% confidence intervals 0.56-2.40. There was no linear dose-response. The lack of clear association for red wine intake was consistently observed when we stratified the analyses by CRC stage at diagnosis and cancer site (colon or rectum). Moderate red wine consumption was not associated with reduced risk of colorectal cancer in this population of middle-aged men.

The global regulator Crc plays a multifaceted role in modulation of type III secretion system in Pseudomonas aeruginosa.

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Dong, Yi-Hu; Zhang, Xi-Fen; Zhang, Lian-Hui

2013-02-01

The opportunistic pathogen Pseudomonas aeruginosa utilizes type III secretion system (T3SS) to translocate effector proteins into eukaryotic host cells that subvert normal host cell functions to the benefit of the pathogen, and results in serious infections. T3SS in P. aeruginosa is controlled by a complex system of regulatory mechanisms and signaling pathways. In this study, we described that Crc, an RNA-binding protein, exerts a positive impact on T3SS in P. aeruginosa, as evidenced by promoter activity assays of several key T3SS genes, transcriptomics, RT-PCR, and immunoblotting in crc mutant. We further demonstrated that the regulatory function of Crc on the T3SS was mediated through the T3SS master regulator ExsA and linked to the Cbr/Crc signaling system. Expression profiling of the crc mutant revealed a downregulation of flagship T3SS genes as well as 16 other genes known to regulate T3SS gene expression in P. aeruginosa. On the basis of these data, we proposed that Crc may exert multifaceted control on the T3SS through various pathways, which may serve to fine-tune this virulence mechanism in response to environmental changes and nutrient sources. © 2012 The Authors. Published by Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Mutation spectrum and risk of colorectal cancer in African American families with Lynch syndrome.

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Guindalini, Rodrigo Santa Cruz; Win, Aung Ko; Gulden, Cassandra; Lindor, Noralane M; Newcomb, Polly A; Haile, Robert W; Raymond, Victoria; Stoffel, Elena; Hall, Michael; Llor, Xavier; Ukaegbu, Chinedu I; Solomon, Ilana; Weitzel, Jeffrey; Kalady, Matthew; Blanco, Amie; Terdiman, Jonathan; Shuttlesworth, Gladis A; Lynch, Patrick M; Hampel, Heather; Lynch, Henry T; Jenkins, Mark A; Olopade, Olufunmilayo I; Kupfer, Sonia S

2015-11-01

African Americans (AAs) have the highest incidence of and mortality resulting from colorectal cancer (CRC) in the United States. Few data are available on genetic and nongenetic risk factors for CRC among AAs. Little is known about cancer risks and mutations in mismatch repair (MMR) genes in AAs with the most common inherited CRC condition, Lynch syndrome. We aimed to characterize phenotype, mutation spectrum, and risk of CRC in AAs with Lynch syndrome. We performed a retrospective study of AAs with mutations in MMR genes (MLH1, MSH2, MSH6, and PMS2) using databases from 13 US referral centers. We analyzed data on personal and family histories of cancer. Modified segregation analysis conditioned on ascertainment criteria was used to estimate age- and sex-specific CRC cumulative risk, studying members of the mutation-carrying families. We identified 51 AA families with deleterious mutations that disrupt function of the MMR gene product: 31 in MLH1 (61%), 11 in MSH2 (21%), 3 in MSH6 (6%), and 6 in PMS2 (12%); 8 mutations were detected in more than 1 individual, and 11 have not been previously reported. In the 920 members of the 51 families with deleterious mutations, the cumulative risks of CRC at 80 years of age were estimated to be 36.2% (95% confidence interval [CI], 10.5%-83.9%) for men and 29.7% (95% CI, 8.31%-76.1%) for women. CRC risk was significantly higher among individuals with mutations in MLH1 or MSH2 (hazard ratio, 13.9; 95% CI, 3.44-56.5). We estimate the cumulative risk for CRC in AAs with MMR gene mutations to be similar to that of individuals of European descent with Lynch syndrome. Two-thirds of mutations were found in MLH1, some of which were found in multiple individuals and some that have not been previously reported. Differences in mutation spectrum are likely to reflect the genetic diversity of this population. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Colorectal cancer screening for average-risk North Americans: an economic evaluation.

Directory of Open Access Journals (Sweden)

Steven J Heitman

Full Text Available BACKGROUND: Colorectal cancer (CRC fulfills the World Health Organization criteria for mass screening, but screening uptake is low in most countries. CRC screening is resource intensive, and it is unclear if an optimal strategy exists. The objective of this study was to perform an economic evaluation of CRC screening in average risk North American individuals considering all relevant screening modalities and current CRC treatment costs. METHODS AND FINDINGS: An incremental cost-utility analysis using a Markov model was performed comparing guaiac-based fecal occult blood test (FOBT or fecal immunochemical test (FIT annually, fecal DNA every 3 years, flexible sigmoidoscopy or computed tomographic colonography every 5 years, and colonoscopy every 10 years. All strategies were also compared to a no screening natural history arm. Given that different FIT assays and collection methods have been previously tested, three distinct FIT testing strategies were considered, on the basis of studies that have reported "low," "mid," and "high" test performance characteristics for detecting adenomas and CRC. Adenoma and CRC prevalence rates were based on a recent systematic review whereas screening adherence, test performance, and CRC treatment costs were based on publicly available data. The outcome measures included lifetime costs, number of cancers, cancer-related deaths, quality-adjusted life-years gained, and incremental cost-utility ratios. Sensitivity and scenario analyses were performed. Annual FIT, assuming mid-range testing characteristics, was more effective and less costly compared to all strategies (including no screening except FIT-high. Among the lifetimes of 100,000 average-risk patients, the number of cancers could be reduced from 4,857 to 1,393 [corrected] and the number of CRC deaths from 1,782 [corrected] to 457, while saving CAN$68 per person. Although screening patients with FIT became more expensive than a strategy of no screening when the

Consumption of Whole-Grain Bread and Risk of Colorectal Cancer among Norwegian Women (the NOWAC Study).

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Bakken, Toril; Braaten, Tonje; Olsen, Anja; Kyrø, Cecilie; Lund, Eiliv; Skeie, Guri

2016-01-13

There is evidence that consumption of foods containing dietary fiber decreases the risk of colorectal cancer (CRC). Whole grains contain dietary fiber, as well as a range of micronutrients and bioactive compounds, but the association between the consumption of whole grains and the risk of CRC remains less studied. The aim of the present study was to investigate the association between whole-grain bread consumption and CRC incidence among Norwegian women, using data from a prospective cohort study (the Norwegian Women and Cancer Study). Dietary intake was estimated from the food-frequency questionnaires of 78,254 women in the cohort (median age: 55 years), and these women were then followed up for CRC incidence. During the 9 years of median follow-up, 795 women were diagnosed with CRC (316 proximal, 193 distal, 218 rectal). Associations between whole-grain bread consumption and the risk of CRC (including colorectal subsites) were investigated using Cox proportional hazards regression models. When compared to the low consumption group, the hazard ratio for CRC was 0.89 (95% confidence interval (CI): 0.72-1.09) for the high consumption group and 0.86 (95% CI: 0.72-1.02) for the medium consumption group in a multivariable model. Overall, no association between whole-grain bread consumption and CRC was found.

Improving diagnosis, prognosis and prediction by using biomarkers in CRC patients (Review).

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Nikolouzakis, Taxiarchis Konstantinos; Vassilopoulou, Loukia; Fragkiadaki, Persefoni; Mariolis Sapsakos, Theodoros; Papadakis, Georgios Z; Spandidos, Demetrios A; Tsatsakis, Aristides M; Tsiaoussis, John

2018-06-01

Colorectal cancer (CRC) is among the most common cancers. In fact, it is placed in the third place among the most diagnosed cancer in men, after lung and prostate cancer, and in the second one for the most diagnosed cancer in women, following breast cancer. Moreover, its high mortality rates classifies it among the leading causes of cancer‑related death worldwide. Thus, in order to help clinicians to optimize their practice, it is crucial to introduce more effective tools that will improve not only early diagnosis, but also prediction of the most likely progression of the disease and response to chemotherapy. In that way, they will be able to decrease both morbidity and mortality of their patients. In accordance with that, colon cancer research has described numerous biomarkers for diagnostic, prognostic and predictive purposes that either alone or as part of a panel would help improve patient's clinical management. This review aims to describe the most accepted biomarkers among those proposed for use in CRC divided based on the clinical specimen that is examined (tissue, faeces or blood) along with their restrictions. Lastly, new insight in CRC monitoring will be discussed presenting promising emerging biomarkers (telomerase activity, telomere length and micronuclei frequency).

Influence of smoking, body mass index and other factors on the preventive effect of nonsteroidal anti-inflammatory drugs on colorectal cancer risk.

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Wang, Xiaoliang; Chan, Andrew T; Slattery, Martha L; Chang-Claude, Jenny; Potter, John D; Gallinger, Steven; Caan, Bette; Lampe, Johanna W; Newcomb, Polly A; Zubair, Niha; Hsu, Li; Schoen, Robert E; Hoffmeister, Michael; Brenner, Hermann; Le Marchand, Loic; Peters, Ulrike; White, Emily

2018-06-19

Nonsteroidal anti-inflammatory drugs (NSAIDs) use has consistently been associated with lower risk of colorectal cancer (CRC); however, studies showed inconsistent results on which cohort of individuals may benefit most. We performed multivariable logistic regression analysis to systematically test for the interaction between regular use of NSAIDs and other lifestyle and dietary factors on CRC risk among 11,894 cases and 15,999 controls. Fixed-effects meta-analyses were used for stratified analyses across studies for each risk factor and to summarize the estimates from interactions. Regular use of any NSAID, aspirin, or non-aspirin NSAIDs was significantly associated with a lower risk of CRC within almost all subgroups. However, smoking status and BMI were found to modify the NSAID-CRC association. Aspirin use was associated with a 29% lower CRC risk among never-smokers (OR = 0.71; 95% CI: 0.64, 0.79), compared to 19% and 17% lower CRC risk among smokers of pack-years below median (OR = 0.81; 95% CI: 0.71, 0.92) and above median (OR = 0.83; 95% CI: 0.74, 0.94), respectively (p-interaction = 0.048). The association between any NSAID use and CRC risk was also attenuated with increasing BMI (p-interaction = 0.075). Collectively, these results suggest that obese individuals and heavy smokers are unlikely to benefit as much as other groups from the prophylactic effect of aspirin against CRC. Copyright ©2018, American Association for Cancer Research.

Expression of the MAP kinase phosphatase DUSP4 is associated with microsatellite instability in colorectal cancer (CRC) and causes increased cell proliferation.

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Gröschl, Benedikt; Bettstetter, Marcus; Giedl, Christian; Woenckhaus, Matthias; Edmonston, Tina; Hofstädter, Ferdinand; Dietmaier, Wolfgang

2013-04-01

DUSP4 (MKP-2), a member of the mitogen-activated protein kinase phosphatase (MKP) family and potential tumor suppressor, negatively regulates the MAPKs (mitogen-activated protein kinases) ERK, p38 and JNK. MAPKs play a crucial role in cancer development and progression. Previously, using microarray analyses we found a conspicuously frequent overexpression of DUSP4 in colorectal cancer (CRC) with high frequent microsatellite instability (MSI-H) compared to microsatellite stable (MSS) CRC. Here we studied DUSP4 expression on mRNA level in 38 CRC (19 MSI-H and 19 MSS) compared to matched normal tissue as well as in CRC cell lines by RT-qPCR. DUSP4 was overexpressed in all 19 MSI-H tumors and in 14 MSS tumors. Median expression levels in MSI-H tumors were significantly higher than in MSS-tumors (p CRC cell lines showed 6.8-fold higher DUSP4 mRNA levels than MSS cell lines. DUSP4 expression was not regulated by promoter methylation since no methylation was found by quantitative methylation analysis of DUSP4 promoter in CRC cell lines neither in tumor samples. Furthermore, no DUSP4 mutation was found on genomic DNA level in four CRC cell lines. DUSP4 overexpression in CRC cell lines through DUSP4 transfection caused upregulated expression of MAPK targets CDC25A, CCND1, EGR1, FOS, MYC and CDKN1A in HCT116 as well as downregulation of mismatch repair gene MSH2 in SW480. Furthermore, DUSP4 overexpression led to increased proliferation in CRC cell lines. Our findings suggest that DUSP4 acts as an important regulator of cell growth within the MAPK pathway and causes enhanced cell growth in MSI-H CRC. Copyright © 2012 UICC.

A DASH dietary pattern and the risk of colorectal cancer in Canadian adults

OpenAIRE

Jones-McLean, E.; Hu, J.; Greene-Finestone, L. S.; de Groh, M.

2015-01-01

Introduction: Colorectal cancer (CRC) is a high incidence cancer affecting many Canadian adults each year. Diet is important in the etiology of CRC with many dietary components identified as potential risk factors. The Dietary Approaches to Stop Hypertension (DASH) diet is a well-established pattern to characterize overall eating. The purpose of this study was to characterize a DASH pattern within the Canadian context and to assess its relationship to the risk of CRC in Canadian adults. Metho...

The Crc protein inhibits the production of polyhydroxyalkanoates in Pseudomonas putida under balanced carbon/nitrogen growth conditions.

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La Rosa, Ruggero; de la Peña, Fernando; Prieto, María Axiliadora; Rojo, Fernando

2014-01-01

Pseudomonas putida synthesizes polyhydroxyalkanoates (PHAs) as storage compounds. PHA synthesis is more active when the carbon source is in excess and the nitrogen source is limiting, but can also occur at a lower rate under balanced carbon/nitrogen ratios. This work shows that PHA synthesis is controlled by the Crc global regulator, a protein that optimizes carbon metabolism by inhibiting the expression of genes involved in the use of non-preferred carbon sources. Crc acts post-transcriptionally. The mRNAs of target genes contain characteristic catabolite activity (CA) motifs near the ribosome binding site. Sequences resembling CA motifs can be predicted for the phaC1 gene, which codes for a PHA polymerase, and for phaI and phaF, which encode proteins associated to PHA granules. Our results show that Crc inhibits the translation of phaC1 mRNA, but not that of phaI or phaF, reducing the amount of PHA accumulated in the cell. Crc inhibited PHA synthesis during exponential growth in media containing a balanced carbon/nitrogen ratio. No inhibition was seen when the carbon/nitrogen ratio was imbalanced. This extends the role of Crc beyond that of controlling the hierarchical utilization of carbon sources and provides a link between PHA synthesis and the global regulatory networks controlling carbon flow. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

A DASH dietary pattern and the risk of colorectal cancer in Canadian adults

Directory of Open Access Journals (Sweden)

E. Jones-McLean

2015-03-01

Full Text Available Introduction: Colorectal cancer (CRC is a high incidence cancer affecting many Canadian adults each year. Diet is important in the etiology of CRC with many dietary components identified as potential risk factors. The Dietary Approaches to Stop Hypertension (DASH diet is a well-established pattern to characterize overall eating. The purpose of this study was to characterize a DASH pattern within the Canadian context and to assess its relationship to the risk of CRC in Canadian adults. Methods: Unconditional multiple logistic regression with control for confounding variables was performed using data from the National Enhanced Cancer Surveillance Study. Dietary intake was captured for this case-control study through a food frequency questionnaire (FFQ and categorized into a DASH score ranging from 0 to 10 representing a poor to a strong DASH pattern respectively. Results: Consuming a strong DASH pattern of eating (score ≥ 8 was not common in the 3161 cases and 3097 controls. Overall, only 10.8 % of men and 13.6 % of women had a strong DASH pattern. Multivariate analysis demonstrated a trend for decreasing risk of CRC in men with increasing DASH scores (p value for trend = .007. Men with a strong DASH score had a 33% reduction in risk of CRC compared to those with a low DASH score. There were no significant trends for women for CRC or for colon or rectal cancers separately. Conclusion: Our findings are similar to other researchers suggesting a benefit with a strong DASH pattern associated with a decreased risk of CRC, especially in men. Research should further investigate our gender-based differences.

Cancer risks for MLH1 and MSH2 mutation carriers

OpenAIRE

Dowty, James G.; Win, Aung K.; Buchanan, Daniel D.; Lindor, Noralane M.; Macrae, Finlay A.; Clendenning, Mark; Antill, Yoland C.; Thibodeau, Stephen N.; Casey, Graham; Gallinger, Steve; Le Marchand, Loic; Newcomb, Polly A.; Haile, Robert W.; Young, Graeme P.; James, Paul A.

2013-01-01

We studied 17,576 members of 166 MLH1 and 224 MSH2 mutation-carrying families from the Colon Cancer Family Registry. Average cumulative risks of colorectal cancer (CRC), endometrial cancer (EC) and other cancers for carriers were estimated using modified segregation analysis conditioned on ascertainment criteria. Heterogeneity in risks was investigated using a polygenic risk modifier. Average CRC cumulative risks to age 70 years (95% confidence intervals) for MLH1 and MSH2 mutation carriers, ...

The translational repressor Crc controls the Pseudomonas putida benzoate and alkane catabolic pathways using a multi-tier regulation strategy.

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Hernández-Arranz, Sofía; Moreno, Renata; Rojo, Fernando

2013-01-01

Metabolically versatile bacteria usually perceive aromatic compounds and hydrocarbons as non-preferred carbon sources, and their assimilation is inhibited if more preferable substrates are available. This is achieved via catabolite repression. In Pseudomonas putida, the expression of the genes allowing the assimilation of benzoate and n-alkanes is strongly inhibited by catabolite repression, a process controlled by the translational repressor Crc. Crc binds to and inhibits the translation of benR and alkS mRNAs, which encode the transcriptional activators that induce the expression of the benzoate and alkane degradation genes respectively. However, sequences similar to those recognized by Crc in benR and alkS mRNAs exist as well in the translation initiation regions of the mRNA of several structural genes of the benzoate and alkane pathways, which suggests that Crc may also regulate their translation. The present results show that some of these sites are functional, and that Crc inhibits the induction of both pathways by limiting not only the translation of their transcriptional activators, but also that of genes coding for the first enzyme in each pathway. Crc may also inhibit the translation of a gene involved in benzoate uptake. This multi-tier approach probably ensures the rapid regulation of pathway genes, minimizing the assimilation of non-preferred substrates when better options are available. A survey of possible Crc sites in the mRNAs of genes associated with other catabolic pathways suggested that targeting substrate uptake, pathway induction and/or pathway enzymes may be a common strategy to control the assimilation of non-preferred compounds. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

MNS16A tandem repeats minisatellite of human telomerase gene: a risk factor for colorectal cancer.

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Hofer, Philipp; Baierl, Andreas; Feik, Elisabeth; Führlinger, Gerhard; Leeb, Gernot; Mach, Karl; Holzmann, Klaus; Micksche, Michael; Gsur, Andrea

2011-06-01

Telomerase reactivation and expression of human telomerase gene [human telomerase reverse transcriptase (hTERT)] are hallmarks of unlimited proliferation potential of cancer cells. A polymorphic tandem repeats minisatellite of hTERT gene, termed MNS16A was reported to influence hTERT expression. To assess the role of MNS16A as potential biomarker for colorectal cancer (CRC), we investigated for the first time the association of MNS16A genotypes with risk of colorectal polyps and CRC. In the ongoing colorectal cancer study of Austria (CORSA), 3842 Caucasian participants were recruited within a large screening project in the province Burgenland including 90 CRC cases, 308 high-risk polyps, 1022 low-risk polyps and 1822 polyp free controls verified by colonoscopy. MNS16A genotypes were determined by polymerase chain reaction from genomic DNA. Associations of MNS16A genotypes with CRC risk were estimated by logistic regression analysis computing odds ratios (ORs) and 95% confidence intervals (CIs). We identified five different variable number of tandem repeats (VNTRs) of MNS16A including VNTR-364, a newly discovered rare variant. VNTR-274 allele was associated with a 2.7-fold significantly increased risk of CRC compared with the VNTR-302 wild-type (OR = 2.69; 95% CI = 1.11-6.50; P = 0.028). In our CORSA study, the medium length VNTR-274 was identified as risk factor for CRC. Although, this population-based study herewith reports the largest cohort size concerning MNS16A thus far, further large-scale studies in diverse populations are warranted to confirm hTERT MNS16A genotype as potential biomarker for assessment of CRC risk.

The "Interval Walking in Colorectal Cancer" (I-WALK-CRC) study: Design, methods and recruitment results of a randomized controlled feasibility trial.

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Banck-Petersen, Anna; Olsen, Cecilie K; Djurhuus, Sissal S; Herrstedt, Anita; Thorsen-Streit, Sarah; Ried-Larsen, Mathias; Østerlind, Kell; Osterkamp, Jens; Krarup, Peter-Martin; Vistisen, Kirsten; Mosgaard, Camilla S; Pedersen, Bente K; Højman, Pernille; Christensen, Jesper F

2018-03-01

Low physical activity level is associated with poor prognosis in patients with colorectal cancer (CRC). To increase physical activity, technology-based platforms are emerging and provide intriguing opportunities to prescribe and monitor active lifestyle interventions. The "Interval Walking in Colorectal Cancer"(I-WALK-CRC) study explores the feasibility and efficacy a home-based interval-walking intervention delivered by a smart-phone application in order to improve cardio-metabolic health profile among CRC survivors. The aim of the present report is to describe the design, methods and recruitment results of the I-WALK-CRC study.Methods/Results: The I-WALK-CRC study is a randomized controlled trial designed to evaluate the feasibility and efficacy of a home-based interval walking intervention compared to a waiting-list control group for physiological and patient-reported outcomes. Patients who had completed surgery for local stage disease and patients who had completed surgery and any adjuvant chemotherapy for locally advanced stage disease were eligible for inclusion. Between October 1st , 2015, and February 1st , 2017, 136 inquiries were recorded; 83 patients were eligible for enrollment, and 42 patients accepted participation. Age and employment status were associated with participation, as participants were significantly younger (60.5 vs 70.8 years, P CRC survivors was feasible but we aim to better the recruitment rate in future studies. Further, the study clearly favored younger participants. The I-WALK-CRC study will provide important information regarding feasibility and efficacy of a home-based walking exercise program in CRC survivors.

The β-catenin E3 ubiquitin ligase SIAH-1 is regulated by CSN5/JAB1 in CRC cells.

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Jumpertz, Sandra; Hennes, Thomas; Asare, Yaw; Vervoorts, Jörg; Bernhagen, Jürgen; Schütz, Anke K

2014-09-01

COP9 signalosome subunit 5 (CSN5) plays a decisive role in cellular processes such as cell cycle regulation and apoptosis via promoting protein degradation, gene transcription, and nuclear export. CSN5 regulates cullin-RING-E3 ligase (CRL) activity through its deNEDDylase function. It is overexpressed in several tumor entities, but its role in colorectal cancer (CRC) is poorly understood. Wnt/β-catenin signaling is aberrant in most CRC cells, resulting in increased levels of oncogenic β-catenin and thus tumor progression. Under physiological conditions, β-catenin levels are tightly regulated by continuous proteasomal degradation. We recently showed that knockdown of CSN5 in model and CRC cells results in decreased (phospho)-β-catenin levels. Reduced β-catenin levels were associated with an attenuated proliferation rate of different CRC cell types after CSN5 knockdown. The canonical Wnt pathway involves degradation of β-catenin by a β-TrCP1-containing E3 ligase, but is mostly non-functional in CRC cells. We thus hypothesized that alternative β-catenin degradation mediated by SIAH-1 (seven in absentia homolog-1), is responsible for the effect of CSN5 on β-catenin signaling in CRC cells. We found that SIAH-1 plays an essential role in β-catenin degradation in HCT116 CRC cells and that CSN5 affects β-catenin target gene expression in these cells. Of note, CSN5 affected SIAH-1 mRNA and SIAH-1 protein levels. Moreover, β-catenin and SIAH-1 form protein complexes with CSN5 in HCT116 cells. Lastly, we demonstrate that CSN5 promotes SIAH-1 degradation in HCT116 and SW480 cells and that this is associated with its deNEDDylase activity. In conclusion, we have identified a CSN5/β-catenin/SIAH-1 interaction network that might control β-catenin degradation in CRC cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study.

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Moskal, Aurélie; Freisling, Heinz; Byrnes, Graham; Assi, Nada; Fahey, Michael T; Jenab, Mazda; Ferrari, Pietro; Tjønneland, Anne; Petersen, Kristina En; Dahm, Christina C; Hansen, Camilla Plambeck; Affret, Aurélie; Boutron-Ruault, Marie-Christine; Cadeau, Claire; Kühn, Tilman; Katzke, Verena; Iqbal, Khalid; Boeing, Heiner; Trichopoulou, Antonia; Bamia, Christina; Naska, Androniki; Masala, Giovanna; de Magistris, Maria Santucci; Sieri, Sabina; Tumino, Rosario; Sacerdote, Carlotta; Peeters, Petra H; Bueno-de-Mesquita, Bas H; Engeset, Dagrun; Licaj, Idlir; Skeie, Guri; Ardanaz, Eva; Buckland, Genevieve; Castaño, José M Huerta; Quirós, José R; Amiano, Pilar; Molina-Portillo, Elena; Winkvist, Anna; Myte, Robin; Ericson, Ulrika; Sonestedt, Emily; Perez-Cornago, Aurora; Wareham, Nick; Khaw, Kay-Tee; Huybrechts, Inge; Tsilidis, Konstantinos K; Ward, Heather; Gunter, Marc J; Slimani, Nadia

2016-11-22

Much of the current literature on diet-colorectal cancer (CRC) associations focused on studies of single foods/nutrients, whereas less is known about nutrient patterns. We investigated the association between major nutrient patterns and CRC risk in participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Among 477 312 participants, intakes of 23 nutrients were estimated from validated dietary questionnaires. Using results from a previous principal component (PC) analysis, four major nutrient patterns were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed for the association of each of the four patterns and CRC incidence using multivariate Cox proportional hazards models with adjustment for established CRC risk factors. During an average of 11 years of follow-up, 4517 incident cases of CRC were documented. A nutrient pattern characterised by high intakes of vitamins and minerals was inversely associated with CRC (HR per 1 s.d.=0.94, 95% CI: 0.92-0.98) as was a pattern characterised by total protein, riboflavin, phosphorus and calcium (HR (1 s.d.)=0.96, 95% CI: 0.93-0.99). The remaining two patterns were not significantly associated with CRC risk. Analysing nutrient patterns may improve our understanding of how groups of nutrients relate to CRC.

RR-Interval variance of electrocardiogram for atrial fibrillation detection

Science.gov (United States)

Nuryani, N.; Solikhah, M.; Nugoho, A. S.; Afdala, A.; Anzihory, E.

2016-11-01

Atrial fibrillation is a serious heart problem originated from the upper chamber of the heart. The common indication of atrial fibrillation is irregularity of R peak-to-R-peak time interval, which is shortly called RR interval. The irregularity could be represented using variance or spread of RR interval. This article presents a system to detect atrial fibrillation using variances. Using clinical data of patients with atrial fibrillation attack, it is shown that the variance of electrocardiographic RR interval are higher during atrial fibrillation, compared to the normal one. Utilizing a simple detection technique and variances of RR intervals, we find a good performance of atrial fibrillation detection.

Assessing Religious Orientations: Replication and Validation of the Commitment-Reflectivity Circumplex (CRC Model

Directory of Open Access Journals (Sweden)

Steven L. Isaak

2017-09-01

Full Text Available The Commitment-Reflectivity Circumplex (CRC model is a structural model of religious orientation that was designed to help organize and clarify measurement of foundational aspect of religiousness. The current study successfully replicated the CRC model using multidimensional scaling, and further evaluated the reliability, structure, and validity of their measures in both a university student sample (Study 1 and a nationally representative sample (Study 2. All 10 subscales of the Circumplex Religious Orientation Inventory (CROI demonstrated good reliability across both samples. A two-week test-retest of the CROI showed that the subscales are stable over time. A confirmatory factor analysis of the CROI in the representative adult sample demonstrated good model fit. Finally, the CROI’s validity was examined in relation to the Intrinsic, Extrinsic and Quest measures. Overall, the CROI appears to clarify much of the ambiguity inherent in the established scales by breaking down what were very broad orientations into very specific suborientations. The results suggest that the CRC model is applicable for diverse populations of adults. In addition, the CROI appears to be construct valid with good structural and psychometric properties across all 10 subscales.

Coding variants in NOD-like receptors: An association study on risk and survival of colorectal cancer.

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Huhn, Stefanie; da Silva Filho, Miguel I; Sanmuganantham, Tharmila; Pichulik, Tica; Catalano, Calogerina; Pardini, Barbara; Naccarati, Alessio; Polakova-Vymetálkova, Veronika; Jiraskova, Katerina; Vodickova, Ludmila; Vodicka, Pavel; Löffler, Markus W; Courth, Lioba; Wehkamp, Jan; Din, Farhat V N; Timofeeva, Maria; Farrington, Susan M; Jansen, Lina; Hemminki, Kari; Chang-Claude, Jenny; Brenner, Hermann; Hoffmeister, Michael; Dunlop, Malcolm G; Weber, Alexander N R; Försti, Asta

2018-01-01

Nod-like receptors (NLRs) are important innate pattern recognition receptors and regulators of inflammation or play a role during development. We systematically analysed 41 non-synonymous single nucleotide polymorphisms (SNPs) in 21 NLR genes in a Czech discovery cohort of sporadic colorectal cancer (CRC) (1237 cases, 787 controls) for their association with CRC risk and survival. Five SNPs were found to be associated with CRC risk and eight with survival at 5% significance level. In a replication analysis using data of two large genome-wide association studies (GWASs) from Germany (DACHS: 1798 cases and 1810 controls) and Scotland (2210 cases and 9350 controls) the associations found in the Czech discovery set were not confirmed. However, expression analysis in human gut-related tissues and immune cells revealed that the NLRs associated with CRC risk or survival in the discovery set were expressed in primary human colon or rectum cells, CRC tissue and/or cell lines, providing preliminary evidence for a potential involvement of NLRs in general in CRC development and/or progression. Most interesting was the finding that the enigmatic development-related NLRP5 (also known as MATER) was not expressed in normal colon tissue but in colon cancer tissue and cell lines. Future studies may show whether regulatory variants instead of coding variants might affect the expression of NLRs and contribute to CRC risk and survival.

Perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01).

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Suenaga, Mitsukuni; Fujimoto, Yoshiya; Matsusaka, Satoshi; Shinozaki, Eiji; Akiyoshi, Takashi; Nagayama, Satoshi; Fukunaga, Yosuke; Oya, Masatoshi; Ueno, Masashi; Mizunuma, Nobuyuki; Yamaguchi, Toshiharu

2015-01-01

Perioperative chemotherapy combined with surgery for liver metastases is considered an active strategy in metastatic colorectal cancer (CRC). However, its impact on initially unresectable, previously untreated advanced CRC, regardless of concurrent metastases, remains to be clarified. A Phase II study was conducted to evaluate the safety and efficacy of perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced CRC. Patients with previously untreated advanced colon or rectal cancer initially diagnosed as unresectable advanced CRC (TNM stage IIIb, IIIc, or IV) but potentially resectable after neoadjuvant chemotherapy (NAC) were studied. Preoperatively, patients received six cycles of NAC (five cycles of neoadjuvant FOLFOX4 plus bevacizumab followed by one cycle of FOLFOX4 alone). The interval between the last dose of bevacizumab and surgery was at least 5 weeks. Six cycles of adjuvant FOLFOX4 plus bevacizumab were given after surgery. The completion rate of NAC and feasibility of curative surgery were the primary endpoints. An interim analysis was performed at the end of NAC in the 12th patient to assess the completion rate of NAC. The median follow-up time was 56 months. The characteristics of the patients were as follows: sex, eight males and four females; tumor location, sigmoid colon in three, ascending colon in one, and rectum (above the peritoneal reflection) in eight; stage, III in eight and IV in four (liver or lymph nodes). All patients completed six cycles of NAC. There were no treatment-related severe adverse events or deaths. An objective response to NAC was achieved in nine patients (75%), and no disease progression was observed. Eleven patients underwent curative tumor resection, including metastatic lesions. In December 2012, this Phase II study was terminated because of slow registration. Perioperative FOLFOX4 plus bevacizumab is well tolerated and has a promising response rate leading to curative surgery, which offers a survival

Association between glutathione S-transferase M1 and T1 polymorphisms and colorectal cancer risk in patients from Kazakhstan.

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Zhunussova, Gulnur; Zhunusbekova, Benazir; Djansugurova, Leyla

2015-01-01

Colorectal cancer (CRC) is one of the most common malignancies worldwide and the incidence is increasing in developed as well as developing countries including Kazakhstan. Glutathione S-transferases (GSTs) are considered to be cancer susceptibility genes as they play a role in the detoxification of carcinogenic species. In this case-control study the influence of GSTM1 and GSTT1 polymorphisms on CRC risk in Kazakhstan population were evaluated. Blood samples were collected from patients diagnosed with rectal or colon cancer (300 individuals) as well as a control cohort of healthy volunteers (300 individuals), taking into account the age, gender, ethnicity, and smoking habits of the CRC patients. Deletion polymorphisms were genotyped employing a multiplex PCR amplification method. Association between polymorphisms and CRC susceptibility risk was calculated using multivariate analysis and logistic regression for odd ratio (OR). The homozygous GSTM1 null genotype was associated with significantly increased risk of CRC (OR = 2.01, 95% CI = 1.45-2.79, p = 0.0001) while the homozygous GSST1 null genotype was not associated with the risk of developing CRC (OR = 1.10, 95% CI = 0.78-1.55, p = 0.001), but the heterozygous genotype correlated with CRC susceptibility (OR = 1.98, 95% CI = 1.30-3.00, p = 0.001). Also, separate analyses of each of the main ethnic groups (Kazakh and Russian) showed a strong association of GSTM1 null genotype with CRC risk (for Kazakhs OR = 2.36, 95% CI = 1.35-4.10, p = 0.006 and for Russians OR = 1.84, 95% CI = 1.17-2.89, p = 0.003). The CRC risk of GSTM1 null genotype in smokers was considerably higher (OR = 3.37, 95% CI = 1.78-6.38, p = 0.0007). The combination of the GSTM1 and GSTT1 null genotypes in combined mixed population of Kazakhstan showed a trend to increasing the risk of developing CRC (OR = 1.60, 95% CI = 1.00-2.56), but it was not statistically significant. In conclusion, the results of this case-control study for sporadic cases of

The role of RCAS1 as a biomarker in diagnosing CRC and monitoring tumor recurrence and metastasis.

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Han, Su-xia; Wang, Jing; Wang, Li-juan; Jin, Gui-hua; Ying, Xia; He, Chen-chen; Guo, Xi-jing; Zhang, Jian-ying; Zhang, Ying; Zhu, Qing

2014-06-01

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) plays an important role in tumor progression by helping tumor cell to escape from host immunological surveillance or modifying the characteristics of connective tissue around. RCAS1 may appropriately reflect the development and prognosis of tumor. In the study, we sought to identify the clinical significance of RCAS1 in colorectal cancer (CRC) diagnosis and tumor recurrence monitoring. Immunohistochemistry (IHC) with tissue array slides was preformed to analyze RCAS1 protein expression in CRC, colorectal polyps, and normal colon tissues. RCAS1 levels in colorectal cancer were significantly higher than those in colorectal polyps and normal colon tissues (PCRC are significantly higher than in healthy controls and polyps (PCRC was 82.1 %, which was higher than carcinoembryonic antigen (CEA). Especially in CEA-negative cases, the sensitivity of RCAS1 was 88.2 %. Finally, CRC patients who were followed up showed a serum RCAS1 level which significantly decreased after surgery (PCRC diagnosis but also useful for monitoring tumor recurrence. RCAS1 might be a supplementary serological marker for CRC.

Co-Care: A Registry for Individuals at Increased Risk for Colorectal Cancer.

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Sperling, Dylan; Jandorf, Lina; Sriphanlop, Pathu; Martinez, Clarissa; Brown, Karen L; Soper, Emily R; Hiraki, Susan; Itzkowitz, Steven H

2017-01-01

INTRODUCTION: Colorectal cancer (CRC) is one of the leading causes of cancer death for both men and women in the United States. Several factors can increase one’s risk of CRC, including a personal or family history of CRC, a diagnosis or family history of a hereditary colon cancer syndrome, or a diagnosis of chronic inflammatory bowel disease. The purpose of this project was to create a colorectal cancer registry (Co-Care) for individuals with a personal or family history of CRC, and those with disorders of the colon or rectum that are associated with an increased risk for developing CRC. Methods: To be eligible for the registry, patients either had a personal or family history of CRC, a diagnosis or family history of Lynch syndrome, familial adenomatous polyposis, or a diagnosis of Crohn’s colitis or ulcerative colitis with dysplasia. Participants were recruited after seeing their gastroenterologist or genetic counselor, or after undergoing a full or partial colectomy at Mount Sinai Hospital in New York City. Eligible patients who agreed to participate were interviewed by a member of the research staff and asked a wide range of questions pertaining to CRC risk. RESULTS: A total of 224 patients were enrolled in the registry. Participants are mostly white, born in the United States, and married, with a bachelor’s or graduate degree, reporting an annual household income of $100,000 or more. The largest portion have a family history of CRC (27.2%), and almost half of participants are of Jewish descent (46.2%) and have undergone full or partial colectomy (48.2%). More than half of participants have neither received genetic counseling (54.5%) nor undergone genetic testing (59.7%). Only 3.6% report that they currently smoke cigarettes, and 41.1% consume alcohol at least once per week. Lastly, 18.3%, 10.3%, and 27.7% of participants report that they currently take aspirin, folic acid/folate pills or tablets, or calcium pills/tablets, respectively. CONCLUSIONS: This

No Association between HMOX1 and Risk of Colorectal Cancer and No Interaction with Diet and Lifestyle Factors in a Prospective Danish Case-Cohort Study

DEFF Research Database (Denmark)

Andersen, Vibeke; Kopp, Tine Iskov; Tjønneland, Anne

2015-01-01

A-413T (rs2071746) was assessed in relation to risk of colorectal cancer (CRC) and interactions with diet (red meat, fish, fiber, cereals, fruit and vegetables) and lifestyle (use of non-steroidal anti-inflammatory drug and smoking status) were assessed in a case-cohort study of 928 CRC cases......Red meat is a risk factor for colorectal cancer (CRC). We wanted to evaluate whether a functional polymorphism in the HMOX1 gene encoding heme oxygenase modifies risk of CRC or interacts with diet or lifestyle factors because this would identify heme or heme iron as a risk factor of CRC. The HMOX1...... and a comparison group of 1726 randomly selected participants from a prospective study of 57,053 persons. No association between HMOX1 A-413T and CRC risk was found (TT vs. AA + TA; IRR = 1.15, 95% CI: 0.98-1.36, p = 0.10 for the adjusted estimate). No interactions were found between diet or lifestyle and HMOX1 A...

Consumption of Whole-Grain Bread and Risk of Colorectal Cancer among Norwegian Women (the NOWAC Study)

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Bakken, Toril; Braaten, Tonje; Olsen, Anja; Kyrø, Cecilie; Lund, Eiliv; Skeie, Guri

2016-01-01

There is evidence that consumption of foods containing dietary fiber decreases the risk of colorectal cancer (CRC). Whole grains contain dietary fiber, as well as a range of micronutrients and bioactive compounds, but the association between the consumption of whole grains and the risk of CRC remains less studied. The aim of the present study was to investigate the association between whole-grain bread consumption and CRC incidence among Norwegian women, using data from a prospective cohort study (the Norwegian Women and Cancer Study). Dietary intake was estimated from the food-frequency questionnaires of 78,254 women in the cohort (median age: 55 years), and these women were then followed up for CRC incidence. During the 9 years of median follow-up, 795 women were diagnosed with CRC (316 proximal, 193 distal, 218 rectal). Associations between whole-grain bread consumption and the risk of CRC (including colorectal subsites) were investigated using Cox proportional hazards regression models. When compared to the low consumption group, the hazard ratio for CRC was 0.89 (95% confidence interval (CI): 0.72–1.09) for the high consumption group and 0.86 (95% CI: 0.72–1.02) for the medium consumption group in a multivariable model. Overall, no association between whole-grain bread consumption and CRC was found. PMID:26771634

Consumption of Whole-Grain Bread and Risk of Colorectal Cancer among Norwegian Women (the NOWAC Study

Directory of Open Access Journals (Sweden)

Toril Bakken

2016-01-01

Full Text Available There is evidence that consumption of foods containing dietary fiber decreases the risk of colorectal cancer (CRC. Whole grains contain dietary fiber, as well as a range of micronutrients and bioactive compounds, but the association between the consumption of whole grains and the risk of CRC remains less studied. The aim of the present study was to investigate the association between whole-grain bread consumption and CRC incidence among Norwegian women, using data from a prospective cohort study (the Norwegian Women and Cancer Study. Dietary intake was estimated from the food-frequency questionnaires of 78,254 women in the cohort (median age: 55 years, and these women were then followed up for CRC incidence. During the 9 years of median follow-up, 795 women were diagnosed with CRC (316 proximal, 193 distal, 218 rectal. Associations between whole-grain bread consumption and the risk of CRC (including colorectal subsites were investigated using Cox proportional hazards regression models. When compared to the low consumption group, the hazard ratio for CRC was 0.89 (95% confidence interval (CI: 0.72–1.09 for the high consumption group and 0.86 (95% CI: 0.72–1.02 for the medium consumption group in a multivariable model. Overall, no association between whole-grain bread consumption and CRC was found.

NR2F2 inhibits Smad7 expression and promotes TGF-β-dependent epithelial-mesenchymal transition of CRC via transactivation of miR-21.

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Wang, Hao; Nie, Lei; Wu, Lei; Liu, Qiufang; Guo, Xueyan

2017-03-25

Metastasis is one of the most decisive factors influencing CRC patient prognosis and current studies suggest that a molecular mechanism known as EMT broadly regulates cancer metastasis. NR2F2 is a key molecule in the development of CRC, but the roles and underlying mechanisms of NR2F2 in TGF-β induced EMT in CRC remain largely unknown. In the current study, we were interested to examine the role of NR2F2 in the TGF-β-induced EMT in CRC. Here, we found NR2F2 was upregulated in CRC cells and promotes TGF-β-induced EMT in CRC. Using comparative miRNA profiling TGF-β pre-treated CRC cells in which NR2F2 had been knocked down with that of control cells, we identified miR-21 as a commonly downregulated miRNA in HT29 cells treated with TGF-β and NR2F2 siRNA, and its downregulation inhibiting migration and invasion of CRC cells. Moreover, we found NR2F2 could transcriptional activated miR-21 expression by binding to miR-21 promoter in HT29 by ChIP and luciferase assay. In the last, our data demonstrated that Smad7 was the direct target of miR-21 in CRC cells. Thus, NR2F2 could promote TGF-β-induced EMT and inhibit Smad7 expression via transactivation of miR-21, and NR2F2 may be a new common therapeutic target for CRC. Copyright © 2017 Elsevier Inc. All rights reserved.

The Crc protein participates in down-regulation of the Lon gene to promote rhamnolipid production and rhl quorum sensing in Pseudomonas aeruginosa.

Science.gov (United States)

Yang, Nana; Ding, Shuting; Chen, Feifei; Zhang, Xue; Xia, Yongjie; Di, Hongxia; Cao, Qiao; Deng, Xin; Wu, Min; Wong, Catherine C L; Tian, Xiao-Xu; Yang, Cai-Guang; Zhao, Jing; Lan, Lefu

2015-05-01

Rhamnolipid acts as a virulence factor during Pseudomonas aeruginosa infection. Here, we show that deletion of the catabolite repression control (crc) gene in P. aeruginosa leads to a rhamnolipid-negative phenotype. This effect is mediated by the down-regulation of rhl quorum sensing (QS). We discover that a disruption of the gene encoding the Lon protease entirely offsets the effect of crc deletion on the production of both rhamnolipid and rhl QS signal C4-HSL. Crc is unable to bind lon mRNA in vitro in the absence of the RNA chaperon Hfq, while Crc contributes to Hfq-mediated repression of the lon gene expression at a posttranscriptional level. Deletion of crc, which results in up-regulation of lon, significantly reduces the in vivo stability and abundance of the RhlI protein that synthesizes C4-HSL, causing the attenuation of rhl QS. Lon is also capable of degrading the RhlI protein in vitro. In addition, constitutive expression of rhlI suppresses the defects of the crc deletion mutant in rhamnolipid, C4-HSL and virulence on lettuce leaves. This study therefore uncovers a novel posttranscriptional regulatory cascade, Crc-Hfq/Lon/RhlI, for the regulation of rhamnolipid production and rhl QS in P. aeruginosa. © 2015 John Wiley & Sons Ltd.

Lynch syndrome caused by germline PMS2 mutations: delineating the cancer risk.

Science.gov (United States)

ten Broeke, Sanne W; Brohet, Richard M; Tops, Carli M; van der Klift, Heleen M; Velthuizen, Mary E; Bernstein, Inge; Capellá Munar, Gabriel; Gomez Garcia, Encarna; Hoogerbrugge, Nicoline; Letteboer, Tom G W; Menko, Fred H; Lindblom, Annika; Mensenkamp, Arjen R; Moller, Pal; van Os, Theo A; Rahner, Nils; Redeker, Bert J W; Sijmons, Rolf H; Spruijt, Liesbeth; Suerink, Manon; Vos, Yvonne J; Wagner, Anja; Hes, Frederik J; Vasen, Hans F; Nielsen, Maartje; Wijnen, Juul T

2015-02-01

The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers. Data were collected from 98 PMS2 families ascertained from family cancer clinics that included a total of 2,548 family members and 377 proven mutation carriers. To adjust for potential ascertainment bias, a modified segregation analysis model was used to calculate colorectal cancer (CRC) and endometrial cancer (EC) risks. Standardized incidence ratios (SIRs) were calculated to estimate risks for other Lynch syndrome-associated cancers. The cumulative risk (CR) of CRC for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for CRC and 12% for EC. The mean age of CRC development was 52 years, and there was a significant difference in mean age of CRC between the probands (mean, 47 years; range, 26 to 68 years) and other family members with a PMS2 mutation (mean, 58 years; range, 31 to 86 years; P PMS2 mutation, and it should be noted that we observed a substantial variation in cancer phenotype within and between families, suggesting the influence of genetic modifiers and lifestyle factors on cancer risks. © 2014 by American Society of Clinical Oncology.

The Associations between RNA Splicing Complex Gene SF3A1 Polymorphisms and Colorectal Cancer Risk in a Chinese Population.

Directory of Open Access Journals (Sweden)

Xiaohua Chen

Full Text Available Aberrant alternative splicing included alterations in components of the mRNA splicing machinery often occurred in colon cancer. However, the role of SF3A1, one key component of the mRNA splicing machinery, on colorectal cancer (CRC risk was still not elucidated.We performed a hospital-based case-control study containing 801 CRC patients and 817 cancer-free controls to examine the association between SF3A1 polymorphisms and CRC risk in a Chinese population. Four candidate SNPs (rs10376, rs5753073, rs2839998 and rs2074733 were selected based on bioinformatics analysis and previous findings. The results showed no significant associations between these SNPs and CRC risk (P > 0.05. Besides, the stratified analysis based on the smoking and alcohol use status obtained no statistically significant results.Our study was the first one to investigate the association between SF3A1 polymorphisms and CRC risk. The results suggested these four SNPs in SF3A1 were not associated with CRC risk in a Chinese population, however, further more studies are needed to confirm our findings.

High reflectance Cr/C multilayer at 250 eV for soft X-ray polarimetry

Energy Technology Data Exchange (ETDEWEB)

Wen, Mingwu; Jiang, Li; Zhang, Zhong; Huang, Qiushi [MOE Key Laboratory of Advanced Micro-Structured Materials, Institute of Precision Optical Engineering (IPOE), School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); Wang, Zhanshan, E-mail: wangzs@tongji.edu.cn [MOE Key Laboratory of Advanced Micro-Structured Materials, Institute of Precision Optical Engineering (IPOE), School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); She, Rui; Feng, Hua [Department of Engineering Physics, Tsinghua University, Beijing (China); Wang, Hongchang [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom)

2015-10-01

X-ray reflection near 45° via multilayer mirrors can be used for astronomical polarization measurements. A Cr/C multilayer mirror (designed for X-ray polarimetry at 250 eV), with a period thickness of 3.86 nm and a bi-layer number of 100, was fabricated using direct current magnetron sputtering. Grazing incidence X-ray reflectometry at 8 keV and transmission electron microscopy were used to investigate the multilayer structure. Different models were introduced to fit the hard X-ray reflectivity curve, which indicates that the layer thickness of two materials slightly drifts from the bottom to the top of the stack. Both the chromium and carbon layers are amorphous with asymmetric interfaces, while the Cr-on-C interface is slightly wider. Based on the good quality of the multilayer structure, a high reflectivity of 21.8% for the s-polarized light was obtained at 250 eV at a grazing incidence angle of 40.7°. The fabricated Cr/C multilayer mirror exhibits high reflectivity and polarization levels in the energy region of 240 eV–260 eV. - Highlights: • We fabricated Cr/C multilayer with 3.8 nm d-spacing. • X-ray reflectometry was used to determine the exact structure of Cr/C multilayer. • A high reflectivity of 21.8% for the s-polarized light was obtained at 250 eV. • Both Cr and C were found to be amorphous with slightly asymmetric interfaces. • A 4-layer model was used to fit and explain the results.

Quantitative proteomic analysis of paired colorectal cancer and non-tumorigenic tissues reveals signature proteins and perturbed pathways involved in CRC progression and metastasis.

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Sethi, Manveen K; Thaysen-Andersen, Morten; Kim, Hoguen; Park, Cheol Keun; Baker, Mark S; Packer, Nicolle H; Paik, Young-Ki; Hancock, William S; Fanayan, Susan

2015-08-03

Modern proteomics has proven instrumental in our understanding of the molecular deregulations associated with the development and progression of cancer. Herein, we profile membrane-enriched proteome of tumor and adjacent normal tissues from eight CRC patients using label-free nanoLC-MS/MS-based quantitative proteomics and advanced pathway analysis. Of the 948 identified proteins, 184 proteins were differentially expressed (P1.5) between the tumor and non-tumor tissue (69 up-regulated and 115 down-regulated in tumor tissues). The CRC tumor and non-tumor tissues clustered tightly in separate groups using hierarchical cluster analysis of the differentially expressed proteins, indicating a strong CRC-association of this proteome subset. Specifically, cancer associated proteins such as FN1, TNC, DEFA1, ITGB2, MLEC, CDH17, EZR and pathways including actin cytoskeleton and RhoGDI signaling were deregulated. Stage-specific proteome signatures were identified including up-regulated ribosomal proteins and down-regulated annexin proteins in early stage CRC. Finally, EGFR(+) CRC tissues showed an EGFR-dependent down-regulation of cell adhesion molecules, relative to EGFR(-) tissues. Taken together, this study provides a detailed map of the altered proteome and associated protein pathways in CRC, which enhances our mechanistic understanding of CRC biology and opens avenues for a knowledge-driven search for candidate CRC protein markers. Copyright © 2015 Elsevier B.V. All rights reserved.

THE RR LYRAE VARIABLES AND HORIZONTAL BRANCH OF NGC 6656 (M22) {sup ,}

Energy Technology Data Exchange (ETDEWEB)

Kunder, Andrea; Walker, Alistair R.; Paredes Alvarez, Leonardo [Cerro Tololo Inter-American Observatory, Casilla 603, La Serena (Chile); Stetson, Peter B. [Dominion Astrophysical Observatory, NRC-Herzberg, National Research Council, Victoria BC, V9E 2E7 (Canada); Cassisi, Santi [INAF-Osservatorio Astronomico di Collurania, Via M. Maggini, I-64100 Teramo (Italy); Layden, Andrew [Bowling Green State University, Bowling Green, OH 43403 (United States); Bono, Giuseppe [Dipartimento di Fisica, Universita di Roma Tor Vergata, Rome (Italy); Catelan, Márcio [Pontificia Universidad Católica de Chile, Departamento de Astronomía y Astrofísica, Av. Vicuña Mackenna 4860, 782-0436 Macul, Santiago (Chile); Clem, James L. [Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA 70803-4001 (United States); Matsunaga, Noriyuki [Department of Astronomy, School of Science, The University of Tokyo (Japan); Salaris, Maurizio [Astrophysics Research Institute, Liverpool John Moores University, Twelve Quays House, Egerton Wharf, Birkenhead CH41 1LD (United Kingdom); Lee, Jae-Woo [Korea Astronomy and Space Science Institute, Daejeon 305-348 (Korea, Republic of); Chaboyer, Brian, E-mail: akunder@ctio.noao.edu, E-mail: mcatelan@astro.puc.cl [Department of Physics and Astronomy, Dartmouth College, Hanover, NH 03755 (United States)

2013-11-01

The first calibrated broadband UBVI time-series photometry is presented for the RR Lyrae variable stars in NGC 6656 (M22), with observations spanning a range of 22 years. We have also redetermined the variability types and periods for the RR Lyrae stars identified previously by photographic observations, revising the number of fundamental-mode RR Lyrae variables (RR0) to 10 and the number of first-overtone variables (RR1) to 16. The mean periods of the RR0 and RR1 variables are (P) {sub RR0} = 0.66 ± 0.02 days and (P) {sub RR1} = 0.33 ± 0.01 days, respectively, supporting an Oosterhoff II classification for the cluster. The number ratio of RR1-type to all RR-type variables is N {sub 1}/N{sub RR} = 0.61, also consistent with an Oosterhoff II designation. Both the RR Lyrae stars' minimum light colors and the blue edge of the RR Lyrae instability strip suggest E( B – – V) = 0.36 ± 0.02 mag toward M22. Regarding the HB morphology of M22, we find (B-R)/(B+V+R) = +0.97 ± 0.1 and at least one ''gap'' located in an unusual part of the blue HB, in the middle of the so-called hot HB stars.

Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer

Science.gov (United States)

Lawler, Mark; Alsina, Deborah; Adams, Richard A; Anderson, Annie S; Brown, Gina; Fearnhead, Nicola S; Fenwick, Stephen W; Hochhauser, Daniel; Koelzer, Viktor H; McNair, Angus G K; Norton, Christine; Novelli, Marco R; Steele, Robert J C; Thomas, Anne L; Wilde, Lisa M; Wilson, Richard H

2018-01-01

Objective Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes. Design RG analysis was conducted by a multidisciplinary panel of patients, clinicians and researchers (n=71). Eight working groups (WG) were constituted: discovery science; risk; prevention; early diagnosis and screening; pathology; curative treatment; stage IV disease; and living with and beyond CRC. A series of discussions led to development of draft papers by each WG, which were evaluated by a 20-strong patient panel. A final list of RGs and research recommendations (RR) was endorsed by all participants. Results Fifteen critical RGs are summarised below: RG1: Lack of realistic models that recapitulate tumour/tumour micro/macroenvironment; RG2: Insufficient evidence on precise contributions of genetic/environmental/lifestyle factors to CRC risk; RG3: Pressing need for prevention trials; RG4: Lack of integration of different prevention approaches; RG5: Lack of optimal strategies for CRC screening; RG6: Lack of effective triage systems for invasive investigations; RG7: Imprecise pathological assessment of CRC; RG8: Lack of qualified personnel in genomics, data sciences and digital pathology; RG9: Inadequate assessment/communication of risk, benefit and uncertainty of treatment choices; RG10: Need for novel technologies/interventions to improve curative outcomes; RG11: Lack of approaches that recognise molecular interplay between metastasising tumours and their microenvironment; RG12: Lack of reliable biomarkers to guide stage IV treatment; RG13: Need to increase understanding of health related quality of life (HRQOL) and promote residual symptom resolution; RG14: Lack of coordination of CRC research/funding; RG15: Lack of effective communication between relevant stakeholders. Conclusion Prioritising research activity and funding could have a significant impact on reducing CRC

Risk Factors Associated with Colorectal Cancer in a Subset of Patients with Mutations in MLH1 and MSH2 in Taiwan Fulfilling the Amsterdam II Criteria for Lynch Syndrome.

Directory of Open Access Journals (Sweden)

Abram Bunya Kamiza

Full Text Available Lynch syndrome, caused by germline mutations in mismatch repair genes, is a predisposing factor for colorectal cancer (CRC. This retrospective cohort study investigated the risk factors associated with the development of CRC in patients with MLH1 and MSH2 germline mutations.In total, 301 MLH1 and MSH2 germline mutation carriers were identified from the Amsterdam criteria family registry provided by the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A Cox proportional hazard model was used to calculate the hazard ratios (HRs and 95% confidence intervals (CIs to determine the association between the risk factors and CRC development. A robust sandwich covariance estimation model was used to evaluate family dependence.Among the total cohort, subjects of the Hakka ethnicity exhibited an increased CRC risk (HR = 1.62, 95% CI = 1.09-2.34; however, those who performed regular physical activity exhibited a decreased CRC risk (HR = 0.62, 95% CI = 0.41-0.88. The CRC risk was enhanced in MLH1 germline mutation carriers, with corresponding HRs of 1.72 (95% CI = 1.16-2.55 and 0.54 (95% CI = 0.34-0.83 among subjects of the Hakka ethnicity and those who performed regular physical activity, respectively. In addition, the total cohort with a manual occupation had a 1.56 times higher CRC risk (95% CI = 1.07-2.27 than did that with a skilled occupation. Moreover, MSH2 germline mutation carriers with blood group type B exhibited an increased risk of CRC development (HR = 2.64, 95% CI = 1.06-6.58 compared with those with blood group type O.The present study revealed that Hakka ethnicity, manual occupation, and blood group type B were associated with an increased CRC risk, whereas regular physical activity was associated with a decreased CRC risk in MLH1 and MSH2 germline mutation carriers.

Evaluating the impact of an educational intervention to increase CRC screening rates in the African American community: a preliminary study.

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Philip, Errol J; DuHamel, Katherine; Jandorf, Lina

2010-10-01

Despite the acknowledged importance of colorectal cancer (CRC) screening and its proven prognostic benefit, African American men and women simultaneously possess the highest rates of CRC-related incidence and mortality (Swan et al. in Cancer 97(6):1528-1540, 2003) and lowest screening rates in the United States (Polite et al. in Med Clin N Am 89(4):771-793, 2005). Effective, targeted interventions that promote CRC screening for this community are therefore critical. The current study evaluated the impact of a print-based educational intervention on screening behavior and associated patient-based factors, including cancer-related knowledge, fatalism, worry, and decisional balance (pros-cons). One hundred and eighteen individuals (mean age = 56.08, SD = 5.58) who had not undergone screening were recruited from two health clinics in New York City. Each participant received educational print materials regarding the need for screening, the process of undergoing screening, and the benefits of regular CRC screening. One in four individuals had undergone post-intervention screening at a three-month follow-up. Whereas all participants reported a decrease in cancer-related worry (p benefits and barriers of screening may be critical in the decision to undergo CRC screening. Future interventions to increase CRC-screening rates for this community may be improved by focusing on these patient-based factors.

Diabetes mellitus type 2 and subsite-specific colorectal cancer risk in men and women: results from the Netherlands Cohort Study on diet and cancer

NARCIS (Netherlands)

Kort, S. de; Simons, C.C.; Brandt, P.A. van den; Goldbohm, R.A.; Arts, I.C.; Bruine, A.P.; Janssen-Heijnen, M.L.; Sanduleanu, S.; Masclee, A.A.; Weijenberg, M.P.

2016-01-01

Background: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer (CRC); however, studies differentiating between subsites of CRC are limited. We investigated how diabetes mellitus (DM) was associated with subsite-specific CRC risk in men and women. Methods: The

Vegetarianism and colorectal cancer risk in a low-selenium environment: effect modification by selenium status? A possible factor contributing to the null results in British vegetarians.

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Sobiecki, Jakub G

2017-08-01

Despite the consistent findings of lower total cancer incidence in vegetarians than in meat-eaters in the UK, the results of studies of colorectal cancer (CRC) risk in British vegetarians have largely been null. This was in contrast to the hypothesis of a decreased risk of CRC in this population due to null intake of red and processed meats and increased intake of fibre. Although the data are inconsistent, it has been suggested that selenium (Se) status may influence CRC risk. A literature review was performed of studies on CRC risk in vegetarians, Se intakes and status in vegetarians, and changes of Se intakes and status in the UK throughout the follow-up periods of studies on CRC risk in British vegetarians. Vegetarians in the UK and other low-Se areas were found to have low Se intakes and status compared to non-vegetarians. There was some evidence of a reverse J-shaped curve of Se intakes and status in the UK throughout the last three decades. These presumed patterns were followed by the changes in CRC mortality or incidence in British vegetarians during this period. Available data on Se intake and status in British vegetarians, as well as the relationship between their secular changes in the UK and changes in CRC risk in this dietary group, are compatible with the hypothesis that low Se status may contribute to the largely null results of studies of CRC risk in vegetarians in the UK.

Role of genetic & environment risk factors in the aetiology of colorectal cancer in Malaysia.

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Ramzi, Nurul Hanis; Chahil, Jagdish Kaur; Lye, Say Hean; Munretnam, Khamsigan; Sahadevappa, Kavitha Itagi; Velapasamy, Sharmila; Hashim, Nikman Adli Nor; Cheah, Soon Keat; Lim, Gerard Chin Chye; Hussein, Heselynn; Haron, Mohd Roslan; Alex, Livy; Ler, Lian Wee

2014-06-01

Colorectal cancer (CRC) is second only to breast cancer as the leading cause of cancer-related deaths in Malaysia. In the Asia-Pacific area, it is the highest emerging gastrointestinal cancer. The aim of this study was to identify single nucleotide polymorphisms (SNPs) and environmental factors associated with CRC risk in Malaysia from a panel of cancer associated SNPs. In this case-control study, 160 Malaysian subjects were recruited, including both with CRC and controls. A total of 768 SNPs were genotyped and analyzed to distinguish risk and protective alleles. Genotyping was carried out using Illumina's BeadArray platform. Information on blood group, occupation, medical history, family history of cancer, intake of red meat and vegetables, exposure to radiation, smoking and drinking habits, etc was collected. Odds ratio (OR), 95% confidence interval (CI) were calculated. A panel of 23 SNPs significantly associated with colorectal cancer risk was identified (Pexercise were risk factors for CRC, while consumption of fruits and vegetables served as protective factor.

Smoking attenuates the negative association between carotenoids consumption and colorectal cancer risk.

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Chaiter, Y; Gruber, S B; Ben-Amotz, A; Almog, R; Rennert, H S; Fischler, R; Rozen, G; Rennert, G

2009-10-01

Consumption of vegetables and fruits, physical activity, obesity and caloric intake are all strongly related to the risk of colorectal cancer (CRC). The association between dietary intake of carotenoids from vegetables/fruits and risk of CRC in the context of cigarette smoking was studied in a nutritionally diverse population. The study included 1,817 age sex residence-matched case-control pairs from a population-based study in Northern Israel. Data were acquired by food-frequency questionnaire. Individual intake of carotenoid isomers was calculated using an Israeli food content database. Odds ratios (ORs) were calculated using conditional logistic regression models adjusted for known risk factors. Strong inverse associations were found with consumption of 9-cis-beta-carotene (OR = 0.35, 0.26-0.47), all-trans-beta-carotene (OR = 0.58, 0.44-0.76), cis-beta-cryptoxanthin (OR = 0.67, 0.50-0.90), all-trans-zeaxanthin (OR = 0.64, 0.48-0.86), and lutein (OR = 0.74, 0.57-0.96). Lycopene (OR = 2.22, 1.71-2.89) and all-trans-beta-cryptoxanthin (OR = 2.01, 1.48-2.73) were associated with increased risk of CRC. Inverse associations of most carotenoids with CRC, demonstrated in non-smokers, were much attenuated or reversed in past or current smokers with a highly significant interaction term. Consumption of most dietary carotenoids was found to be strongly associated with reduced risk of CRC. However, smoking significantly attenuated or reversed this observed protective effect on CRC occurrence. Smokers should be advised that smoking also hampers the potential health promoting effects of high fruit and vegetable consumption.

An updated meta-analysis on the association of MDM2 SNP309 polymorphism with colorectal cancer risk.

Directory of Open Access Journals (Sweden)

Xue Qin

Full Text Available The mouse double minute 2 (MDM2 gene encodes a phosphoprotein that interacts with P53 and negatively regulates its activity. The SNP309 polymorphism (T-G in the promoter of MDM2 gene has been reported to be associated with enhanced MDM2 expression and tumor development. Studies investigating the association between MDM2 SNP309 polymorphism and colorectal cancer (CRC risk reported conflicting results. We performed a meta-analysis of all available studies to explore the association of this polymorphism with CRC risk.All studies published up to July 2013 on the association between MDM2 SNP309 polymorphism and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Chinese Biomedical Literature database (CBM databases. The association between the MDM2 SNP309 polymorphism and CRC risk was assessed by odds ratios (ORs together with their 95% confidence intervals (CIs.A total of 14 case-control studies including 4460 CRC cases and 4828 controls were identified. We did not find a significant association between the MDM2 SNP309 polymorphism and CRC risk in all genetic models in overall population. However, in subgroup analysis by ethnicity, significant associations were found in Asians (TG vs. TT: OR = 1.197, 95% CI = 1.055-1.358, P=0.005; GG+TG vs. TT: OR = 1.246, 95% CI = 1.106-1.404, P=0.000 and Africans. When stratified by HWE in controls, significantly increased risk was also found among the studies consistent with HWE (TG vs. TT: OR = 1.166, 95% CI = 1.037-1.311, P= 0.010. In subgroup analysis according to p53 mutation status, and gender, no any significant association was detected.The present meta-analysis suggests that the MDM2 is a candidate gene for CRC susceptibility. The MDM2 SNP309 polymorphism may be a risk factor for CRC in Asians.

Hsa-miR-875-5p exerts tumor suppressor function through down-regulation of EGFR in colorectal carcinoma (CRC).

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Zhang, Tiening; Cai, Xun; Li, Qi; Xue, Peng; Chen, Zhixiao; Dong, Xiao; Xue, Ying

2016-07-05

Hsa-miRNA-875-5p (miR-875-5p) has recently been discovered to have anticancer efficacy in different organs. However, the role of miR-875-5p on colorectal carcinoma (CRC) is still ambiguous. In this study, we investigated the role of miR-875-5p on the development of CRC. The results indicated that miR-875-5p was significantly down-regulated in primary tumor tissues and very low levels were found in CRC cell lines. Ectopic expression of miR-875-5p in CRC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4 and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-875-5p induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-875-5p inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene EGFR was revealed to be a putative target of miR-875-5p, which was inversely correlated with miR-875-5p expression in CRC. Taken together, our results demonstrated that miR-875-5p played a pivotal role on CRC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic EGFR.

Germline genetic variants in the Wnt/beta-catenin pathway as predictors of colorectal cancer risk

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Hildebrandt, Michelle A.T.; Reyes, Monica E.; Lin, Moubin; He, Yonggang; Nguyen, Son V.; Hawk, Ernest T.; Wu, Xifeng

2016-01-01

Background The Wnt/beta-catenin signaling pathway plays a key role in stem cell maintenance in the colorectum. Rare high penetrance genetic mutations in components of this pathway result in familial colorectal cancer, yet the impact of common, germline variants remains unknown. Methods We assessed 172 variants in 26 genes from the Wnt/beta-catenin pathway in 809 CRC cases and 814 healthy controls, followed by replication of the top findings in another 691 cases and 775 controls. In silico informatic tools were used to predict functional effects of variants. Results Eighteen SNPs in the pathway were significantly associated with CRC risk (P <0.05) in the discovery phase. We observed a significant dose-response increase in CRC risk by number of risk genotypes carried (P = 4.19 × 10−8). Gene-based analysis implicated CSNK1D (P = 0.014), FZD3 (P = 0.023), and APC (P = 0.027) as significant for CRC risk. In the replication phase, FZD3:rs11775139 remained significantly associated with reduced risk with a pooled OR of 0.85 (95% CI: 0.76–0.94, P = 0.001). Although borderline significant in the replication population, APC:rs2545162 was highly significant in the pooled analysis - OR: 1.42, 95% CI: 1.16–1.74, P =0.00085. Functional assessment identified several potential biological mechanisms underlying these associations. Conclusions Our findings suggest that common germline variants in the Wnt/beta-catenin pathway maybe involved in CRC development. Impact These variants may be informative in CRC risk assessment to identify individuals at increased risk who would be candidates for screening. PMID:26809274

Calcium scores in the risk assessment of an asymptomatic population: implications for airline pilots.

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Wirawan, I Made Ady; Wu, Rodney; Abernethy, Malcolm; Aldington, Sarah; Larsen, Peter D

2014-08-01

This study evaluated whether coronary artery calcium score (CACS) improved cardiovascular disease risk prediction when compared to the New Zealand Cardiovascular Risk Charts (NZ-CRC), and describes the potential utilization of CACS in cardiovascular disease (CVD) risk assessment of pilots. A cross-sectional study was performed among asymptomatic patients who underwent coronary computed tomography angiography at Pacific Radiology Wellington, New Zealand, between August 2007 and July 2012 and had their CACS and CVD risk score calculated. Receiver-operating characteristics (ROC) analyses were used to measure the accuracy of the NZ-CRC and CACS. Reclassification analyses were performed to examine the net reclassification improvement (NRI) of CACS when compared to NZ-CRC. Over a 5-yr study period, 237 male asymptomatic patients with ages ranging from 30 to 69 yr with a mean (SD) of 53.24 (8.18) yr, were included. The area under the ROC curves (AUC) (95% CI) for CACS and NZ-CRC were 0.88 (0.83-0.93) and 0.66 (0.59-0.73), respectively. The NRI (95% CI) of the calcium scores was 0.39 (0.17-0.62). CACS should be assessed in pilots with 5-yr CVD risk scores of 5-10% and 10-15%. CACS has a better accuracy than the NZ-CRC and reclassified a considerable proportion of asymptomatic patients into correct cardiovascular risk categories. An approach on how the CACS should be employed in the cardiovascular risk assessment of airline pilots is noted in this paper.

Fast Foods, Sweets and Beverage Consumption and Risk of Colorectal Cancer: A Case-Control Study in Jordan

Science.gov (United States)

Tayyem, Reema F; Bawadi, Hiba A; Shehadah, Ihab; Bani-Hani, Kamal E; Takruri, Hamed; Al-Jaberi, Tareq; Heath, Dennis D

2018-01-27

Background: The effects of consuming fast foods, sweets and beverages on the development of colorectal cancer (CRC) are unclear. The aim of this case-control study was to assess possible associations between the consumption of different fast foods, sweets and beverages and CRC risk in a Jordanian population. Methods: Two hundred and twenty diagnosed CRC cases and 281 controls were enrolled. Diet history was obtained using a validated quantitative questionnaire. Results: Consumption of some types of fast food, and particularly falafel, was associated with an increased risk of developing CRC. Elevated risk was found for potato and corn chips with an AOR of 4.36 (95%CI: 1.24-15.28) for daily consumption and 3.33 (95%CI: 1.00-11.11) for ≥5 servings/week. Consuming 1-2 or >5 servings per week of fried potatoes or 2-3 servings per week of chicken in sandwiches also increased the risk while exposure to fresh tomato juice and hot pepper sauce on a monthly basis appeared to exert a protective effect. Conclusions: Consumption of fried fast food items was significantly linked with an increased risk of developing CRC in Jordan. Creative Commons Attribution License

IDAS-RR: an incident data base system for research reactors

International Nuclear Information System (INIS)

Matsumoto, Kiyoshi; Kohsaka, Atsuo; Kaminaga, Masanori; Murayama, Youji; Ohnishi, Nobuaki; Maniwa, Masaki.

1990-03-01

An Incident Data Base System for Research Reactors, IDAS-RR, has been developed. IDAS-RR has information about abnormal incidents (failures, transients, accidents, etc.) of research reactors in the world. Data reference, input, editing and other functions of IDAS-RR are menu driven. The routine processing and data base management functions are performed by the system software and hardware. PC-9801 equipment was selected as the hardware because of its portability and popularity. IDAS-RR provides effective reference information for the following activities. 1) Analysis of abnormal incident of research reactors, 2) Detail analysis of research reactor behavior in the abnormal incident for building the knowledge base of the reactor emergency diagnostic system for research reactor, 3) Planning counter-measure for emergency situation in the research reactor. This report is a user's manual of IDAS-RR. (author)

Randomized controlled dissemination study of community-to-clinic navigation to promote CRC screening: Study design and implications.

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Larkey, Linda; Szalacha, Laura; Herman, Patricia; Gonzalez, Julie; Menon, Usha

2017-02-01

Regular screening facilitates early diagnosis of colorectal cancer (CRC) and reduction of CRC morbidity and mortality. Screening rates for minorities and low-income populations remain suboptimal. Provider referral for CRC screening is one of the strongest predictors of adherence, but referrals are unlikely among those who have no clinic home (common among poor and minority populations). This group randomized controlled study will test the effectiveness of an evidence based tailored messaging intervention in a community-to-clinic navigation context compared to no navigation. Multicultural, underinsured individuals from community sites will be randomized (by site) to receive CRC screening education only, or education plus navigation. In Phase I, those randomized to education plus navigation will be guided to make a clinic appointment to receive a provider referral for CRC screening. Patients attending clinic appointments will continue to receive navigation until screened (Phase II) regardless of initial arm assignment. We hypothesize that those receiving education plus navigation will be more likely to attend clinic appointments (H1) and show higher rates of screening (H2) compared to those receiving education only. Phase I group assignment will be used as a control variable in analysis of screening follow-through in Phase II. Costs per screening achieved will be evaluated for each condition and the RE-AIM framework will be used to examine dissemination results. The novelty of our study design is the translational dissemination model that will allow us to assess the real-world application of an efficacious intervention previously tested in a randomized controlled trial. Copyright © 2016. Published by Elsevier Inc.

MicroRNA-466 (miR-466) functions as a tumor suppressor and prognostic factor in colorectal cancer (CRC).

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Tong, Feng; Ying, Youhua; Pan, Haihua; Zhao, Wei; Li, Hongchen; Zhan, Xiaoli

2018-01-17

MicroRNAs (miRNAs) have an important role in the regulation of tumor development and metastasis. In this study, we investigated the clinical and prognostic value as well as biological function of miR-466 in colorectal cancer (CRC). Tumor and adjacent healthy tissues were obtained from 100 patients diagnosed with CRC. miR-466 expression was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). mRNA and protein levels of cyclin D1, apoptosis regulator BAX (BAX), and matrix metalloproteinase-2 (MMP-2) were analyzed by qRT-PCR and Western blot, respectively, in SW-620 CRC cells transfected with miR-466 mimics or negative control miRNA. Effects of miR-466 on SW-620 cell proliferation, cell cycle and apoptosis, and invasion were investigated using CCK-8 assay, flow cytometry and Transwell assay, respectively. miR-466 expression was significantly downregulated in tumor tissues compared to matched adjacent non-tumor tissues. Low expression of miR-466 was significantly correlated with the tumor size, Tumor Node Metastasis stage, lymph node metastasis, and distant metastasis. The overall survival of CRC patients with low miR-466 expression was significantly shorter compared to high-miR-466 expression group (log-rank test: p = 0.0103). Multivariate analysis revealed that low miR-466 expression was associated with poor prognosis in CRC patients. The ectopic expression of miR-466 suppressed cell proliferation and migration/invasion, as well as induced G0/G1 arrest and apoptosis in SW-620 cells. Moreover, the ectopic expression of miR-466 decreased the expression of cyclin D1 and MMP-2, but increased BAX expression in SW-620 cells. In conclusion, our findings demonstrated that miR-466 functions as a suppressor miRNA in CRC and may be used as a prognostic factor in these patients.

Ventricular Cycle Length Characteristics Estimative of Prolonged RR Interval during Atrial Fibrillation

Science.gov (United States)

CIACCIO, EDWARD J.; BIVIANO, ANGELO B.; GAMBHIR, ALOK; EINSTEIN, ANDREW J.; GARAN, HASAN

2014-01-01

Background When atrial fibrillation (AF) is incessant, imaging during a prolonged ventricular RR interval may improve image quality. It was hypothesized that long RR intervals could be predicted from preceding RR values. Methods From the PhysioNet database, electrocardiogram RR intervals were obtained from 74 persistent AF patients. An RR interval lengthened by at least 250 ms beyond the immediately preceding RR interval (termed T0 and T1, respectively) was considered prolonged. A two-parameter scatterplot was used to predict the occurrence of a prolonged interval T0. The scatterplot parameters were: (1) RR variability (RRv) estimated as the average second derivative from 10 previous pairs of RR differences, T13–T2, and (2) Tm–T1, the difference between Tm, the mean from T13 to T2, and T1. For each patient, scatterplots were constructed using preliminary data from the first hour. The ranges of parameters 1 and 2 were adjusted to maximize the proportion of prolonged RR intervals within range. These constraints were used for prediction of prolonged RR in test data collected during the second hour. Results The mean prolonged event was 1.0 seconds in duration. Actual prolonged events were identified with a mean positive predictive value (PPV) of 80% in the test set. PPV was >80% in 36 of 74 patients. An average of 10.8 prolonged RR intervals per 60 minutes was correctly identified. Conclusions A method was developed to predict prolonged RR intervals using two parameters and prior statistical sampling for each patient. This or similar methodology may help improve cardiac imaging in many longstanding persistent AF patients. PMID:23998759

Periodontal disease, tooth loss and colorectal cancer risk: Results from the Nurses' Health Study.

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Momen-Heravi, Fatemeh; Babic, Ana; Tworoger, Shelley S; Zhang, Libin; Wu, Kana; Smith-Warner, Stephanie A; Ogino, Shuji; Chan, Andrew T; Meyerhardt, Jeffrey; Giovannucci, Edward; Fuchs, Charles; Cho, Eunyoung; Michaud, Dominique S; Stampfer, Meir J; Yu, Yau-Hua; Kim, David; Zhang, Xuehong

2017-02-01

Periodontal diseases including tooth loss might increase systemic inflammation, lead to immune dysregulation and alter gut microbiota, thereby possibly influencing colorectal carcinogenesis. Few epidemiological studies have examined the association between periodontal diseases and colorectal cancer (CRC) risk. We collected information on the periodontal disease (defined as history of periodontal bone loss) and number of natural teeth in the Nurses' Health Study. A total of 77,443 women were followed since 1992. We used Cox proportional hazard models to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) after adjustment for smoking and other known risk factors for CRC. We documented 1,165 incident CRC through 2010. Compared to women with 25-32 teeth, the multivariable HR (95% CI) for CRC for women with periodontal disease, HRs for CRC were 0.91 (95% CI 0.74-1.12) for periodontal disease, and 1.22 (95% CI 0.91-1.63) when limited to moderate to severe periodontal disease. The results were not modified by smoking status, body mass index or alcohol consumption. Women with fewer teeth, possibly moderate or severe periodontal disease, might be at a modest increased risk of developing CRC, suggesting a potential role of oral health in colorectal carcinogenesis. © 2016 UICC.

Why Wait Until Our Community Gets Cancer?: Exploring CRC Screening Barriers and Facilitators in the Spanish-Speaking Community in North Carolina.

Science.gov (United States)

Martens, Christa E; Crutchfield, Trisha M; Laping, Jane L; Perreras, Lexie; Reuland, Daniel S; Cubillos, Laura; Pignone, Michael P; Wheeler, Stephanie B

2016-12-01

Colorectal cancer (CRC) is a leading cause of death among Hispanics in the United States. Despite the benefits of CRC screening, many Hispanics are not being screened. Using a combined methodology of focus groups and discrete choice experiment (DCE) surveys, the objectives for this research were as follows: (1) to improve understanding of preferences regarding potential CRC screening program characteristics, and (2) to improve understanding of the barriers and facilitators around CRC screening with the Hispanic, immigrant community in North Carolina. Four gender-stratified focus groups were conducted and DCE surveys were administered to 38 Spanish-speaking individuals across four counties in North Carolina. In-depth content analysis was used to examine the focus group data; descriptive analyses and mean attribute importance scores for cost of screening and follow-up care, travel time, and test options were calculated from DCE data. Data analyses showed that this population has a strong interest in CRC screening but experience barriers such as lack of access to resources, cost uncertainty, and stigma. Some of these barriers are unique to their cultural experiences in the United States, such as an expressed lack of tailored CRC information. Based on the DCE, cost variables were more important than testing options or travel time. This study suggests that Hispanics may have a general awareness of and interest in CRC screening, but multiple barriers prevent them from getting screened. Special attention should be given to designing culturally and linguistically appropriate programs to improve access to healthcare resources, insurance, and associated costs among Hispanics.

Protein kinase C zeta suppresses low- or high-grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring.

Science.gov (United States)

Deevi, Ravi Kiran; Javadi, Arman; McClements, Jane; Vohhodina, Jekaterina; Savage, Kienan; Loughrey, Maurice Bernard; Evergren, Emma; Campbell, Frederick Charles

2018-04-01

Histological grading provides prognostic stratification of colorectal cancer (CRC) by scoring heterogeneous phenotypes. Features of aggressiveness include aberrant mitotic spindle configurations, chromosomal breakage, and bizarre multicellular morphology, but pathobiology is poorly understood. Protein kinase C zeta (PKCz) controls mitotic spindle dynamics, chromosome segregation, and multicellular patterns, but its role in CRC phenotype evolution remains unclear. Here, we show that PKCz couples genome segregation to multicellular morphology through control of interphase centrosome anchoring. PKCz regulates interdependent processes that control centrosome positioning. Among these, interaction between the cytoskeletal linker protein ezrin and its binding partner NHERF1 promotes the formation of a localized cue for anchoring interphase centrosomes to the cell cortex. Perturbation of these phenomena induced different outcomes in cells with single or extra centrosomes. Defective anchoring of a single centrosome promoted bipolar spindle misorientation, multi-lumen formation, and aberrant epithelial stratification. Collectively, these disturbances induce cribriform multicellular morphology that is typical of some categories of low-grade CRC. By contrast, defective anchoring of extra centrosomes promoted multipolar spindle formation, chromosomal instability (CIN), disruption of glandular morphology, and cell outgrowth across the extracellular matrix interface characteristic of aggressive, high-grade CRC. Because PKCz enhances apical NHERF1 intensity in 3D epithelial cultures, we used an immunohistochemical (IHC) assay of apical NHERF1 intensity as an indirect readout of PKCz activity in translational studies. We show that apical NHERF1 IHC intensity is inversely associated with multipolar spindle frequency and high-grade morphology in formalin-fixed human CRC samples. To conclude, defective PKCz control of interphase centrosome anchoring may underlie distinct categories of

Dietary Patterns and Colorectal Cancer Risk: A Review of 17 Years of Evidence (2000-2016).

Science.gov (United States)

Tabung, Fred K; Brown, Lisa S; Fung, Teresa T

2017-12-01

Colorectal cancer (CRC) is a global public health problem, with an estimated 1.4 million cases diagnosed worldwide in 2012. Evidence suggests that diet may be important for primary prevention. The 2017 WCRF/AICR Continuous Update Project on colorectal cancer concluded that there is convincing evidence linking several individual dietary factors with CRC risk but the evidence for dietary patterns was limited and inconclusive. Also, previous reviews and meta-analyses have not critically synthesized various dietary patterns. This review synthesized data from dietary patterns studies over a 17-year period from 2000 to 2016. We included 49 studies (28 cohort and 21 case-control) that examined the association of index-based and empirically-derived dietary patterns and CRC risk. A synthesis of food group components comprising the different index-based and empirically-derived patterns revealed two distinct dietary patterns associated with CRC risk. A "healthy" pattern, generally characterized by high intake of fruits and vegetables, wholegrains, nuts and legumes, fish and other seafood, milk and other dairy products, was associated with lower CRC risk. In contrast, the "unhealthy" pattern, characterized by high intakes of red meat, processed meat, sugar-sweetened beverages, refined grains, desserts and potatoes was associated with higher CRC risk. It is notable that the number of food groups, the intake quantity, the exact types of foods in each food group, differed between populations, yet the two dietary patterns remained consistent across regions, especially in empirically-derived patterns, an indication of the high reproducibility of these patterns. However, findings for CRC risk in both index-based and empirically-derived patterns, differed by sex, with stronger associations among men than women; study design, a higher proportion of case-control studies reported significant findings compared to prospective studies. Consuming a dietary pattern high in fruits and

Rates and predictors of colorectal cancer screening by race among motivated men participating in a prostate cancer risk assessment program

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Hall, Michael J.; Ruth, Karen; Giri, Veda N.

2011-01-01

Background Screening by fecal occult blood test and lower endoscopy have lowered colorectal cancer (CRC) mortality, but compliance gaps persist. Of concern are possible disparities in uptake of CRC screening between White and African American (AA) men. Our goal was to assess for disparities in uptake of CRC screening among men participating in a high-risk prostate cancer clinic. If present, such disparities could support hypotheses for further research examining racial differences in awareness and patient preferences in undergoing CRC screening. Methods Baseline data on a racially diverse cohort of men age 50–69 at increased risk of prostate cancer collected via the prostate cancer risk assessment program (PRAP) at Fox Chase Cancer Center were analyzed. Predictors of uptake of CRC screening were assessed using multivariable logistic regression. Results Compared to Whites, AA men had statistically significantly lower uptake of fecal occult blood testing (AA 49.0% vs White 60.7%, p=0.035), lower endoscopy (AA 44.1% vs White 58.5%, p=0.011), and any CRC screening (AA 66.2% vs White 76.3%, p=0.053). Predictors of uptake of lower endoscopy among AA men included older age (OR 3.61, 95% CI 1.87–6.97), family history of CRC (OR 3.47, 95% CI 1.30–9.25), and insurance status (OR 1.90, 95% CI 1.04–3.46). Conclusion Despite awareness of cancer risk and motivation to seek prostate cancer screening through a specialized prostate cancer risk assessment program, evidence supporting compliance gaps with CRC screening among men was found. Tailored messages to younger AA men with and without a family history of CRC are needed. PMID:21751189

Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test.

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Zorzi, Manuel; Fedeli, Ugo; Schievano, Elena; Bovo, Emanuela; Guzzinati, Stefano; Baracco, Susanna; Fedato, Chiara; Saugo, Mario; Dei Tos, Angelo Paolo

2015-05-01

Colorectal cancer (CRC) screening programmes based on the guaiac faecal occult blood test (gFOBT) reduce CRC-specific mortality. Several studies have shown higher sensitivity with the faecal immunochemical test (FIT) compared with gFOBT. We carried out an ecological study to evaluate the impact of FIT-based screening programmes on CRC mortality. In the Veneto Region (Italy), biennial FIT-based screening programmes that invited 50-69-year-old residents were introduced in different areas between 2002 and 2009. We compared CRC mortality rates from 1995 to 2011 between the areas where screening started in 2002-2004 (early screening areas (ESA)) and areas that introduced the screening in 2008-2009 (late screening areas (LSA)) using Poisson regression models. We also compared available data on CRC incidence rates (1995-2007) and surgical resection rates (2001-2012). Before the introduction of screening, CRC mortality and incidence rates in the two areas were similar. Compared with 1995-2000, 2006-2011 mortality rates were 22% lower in the ESA than in the LSA (rate ratio (RR)=0.78; 95% CI 0.68 to 0.89). The reduction was larger in women (RR=0.64; CI 0.51 to 0.80) than in men (RR=0.87; CI 0.73 to 1.04). In the ESA, incidence and surgery rates peaked during the introduction of the screening programme and then returned to the baseline (2006-2007 incidence) or dropped below initial values (surgery after 2007). FIT-based screening programmes were associated with a significant reduction in CRC mortality. This effect took place much earlier than reported by gFOBT-based trials and observational studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Racial/Ethnic Variations in Colorectal Cancer Screening Self-Efficacy, Fatalism and Risk Perception in a Safety-Net Clinic Population: Implications for Tailored Interventions.

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Lumpkins, Cy; Cupertino, P; Young, K; Daley, C; Yeh, Hw; Greiner, Ka

2013-01-25

Ethnic and racial minority groups in the U.S. receive fewer colorectal cancer (CRC) screening tests and are less likely to be up-to-date with CRC screening than the population as a whole. Access, limited awareness of CRC and barriers may, in part, be responsible for inhibiting widespread adoption of CRC screening among racial and ethnic minority groups. The purpose of this study was to examine the role of self-efficacy, fatalism and CRC risk perception across racial and ethnic groups in a diverse sample. This study was a cross-sectional analysis from baseline measures gathered on a group of patients recruited into a trial to track colorectal cancer screening in underserved adults over 50. Out of 470 Participants, 42% were non-Hispanic; 27% Hispanic and 28% non-Hispanic White. Hispanic and non-Hispanic Blacks were more likely to have fatalistic beliefs about CRC than non-Hispanic Whites. Non-Hispanic Blacks perceived higher risk of getting colon cancer. Self-efficacy for completing CRC screening was higher among Non-Hispanic Blacks than among Hispanics. Racial and ethnic differences in risk perceptions, fatalism and self-efficacy should be taken into consideration in future CRC interventions with marginalized and uninsured populations.

Dietary patterns and risk of colorectal cancer: a systematic review of cohort studies (2000-2011).

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Yusof, Afzaninawati Suria; Isa, Zaleha Md; Shah, Shamsul Azhar

2012-01-01

This systematic review of cohort studies aimed to identify any association between specific dietary patterns and risk of colorectal cancer (CRC). Dietary patterns involve complex interactions of food and nutrients summarizing the total diet or key aspects of the diet for a population under study. This review involves 6 cohort studies of dietary patterns and their association with colorectal cancer. An exploratory or a posteriori approach and a hypothesis-oriented or a priori approach were employed to identify dietary patterns. The dietary pattern identified to be protective against CRC was healthy, prudent, fruits and vegetables, fat reduced/diet foods, vegetables/fish/poultry, fruit/wholegrain/dairy, healthy eating index 2005, alternate healthy eating index, Mediterranean score and recommended food score. An elevated risk of CRC was associated with Western diet, pork processed meat, potatoes, traditional meat eating, and refined grain pattern. The Western dietary pattern which mainly consists of red and processed meat and refined grains is associated with an elevated risk of development of CRC. Protective factors against CRC include a healthy or prudent diet, consisting of vegetables, fruits, fish and poultry.

RR lyrae variable pulsations and the Oosterhoff groups

International Nuclear Information System (INIS)

Cox, A.N.

1981-01-01

It is concluded that Oosterhoff group I clusters have 0.55 M/sub sun/ stars and group II clusters have 0.65 M/sub sun/ stars. The Y value is always about 0.29. Mean log L/L/sub sun/ values are 1.66 and 1.78 giving M/sub bol/ = 0.60 and 0.30 for the RR Lyrae variables in these two groups of clusters. For field RR Lyrae variables at M = approx. 0.5 M/sub sun/ or less, perhaps M/sub bol/ = 0.90 or even larger as Clube and Jones propose. Apparently all evolution is blueward for RR Lyrae variables, and the color overlap of F and 1H pulsators is not real

Degradation of microcystin-RR using boron-doped diamond electrode

International Nuclear Information System (INIS)

Zhang Chunyong; Fu Degang; Gu Zhongze

2009-01-01

Microcystins (MCs), produced by blue-green algae, are one of the most common naturally occurring toxins found in natural environment. The presence of MCs in drinking water sources poses a great threat to people's health. In this study, the degradation behavior of microcystin-RR on boron-doped diamond (BDD) electrode was investigated under galvanostatic conditions. Such parameters as reaction time, supporting electrolyte and applied current density were varied in order to determine their effects on this oxidation process. The experimental results revealed the suitability of electrochemical processes employing BDD electrode for removing MC-RR from the solution. However, the efficient removal of MC-RR only occurred in the presence of sodium chloride that acted as redox mediators and the reaction was mainly affected by the chloride concentration (c NaCl ) and applied current density (I appl ). Full and quick removal of 0.50 μg/ml MC-RR in solution was achieved when the operating conditions of c NaCl and I appl were 20 mM and 46.3 mA/cm 2 , or 35 mM and 18.2 mA/cm 2 respectively. The kinetics for MC-RR degradation followed a pesudo-first order reaction in most cases, indicating the process was under mass transfer control. As a result of its excellent performance, the BDD technology could be considered as a promising alternative to promote the degradation of MC-RR than chlorination in drinking water supplies.

Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis

International Nuclear Information System (INIS)

Botrel, Tobias Engel Ayer; Clark, Luciana Gontijo de Oliveira; Paladini, Luciano; Clark, Otávio Augusto C.

2016-01-01

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined with different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin. This systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus chemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC). Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were overall survival and progression-free survival. Data extracted from the studies were combined by using hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI). The final analysis included 9 trials comprising 3,914 patients. Patients who received the combined treatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003) with heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher overall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse events and severe toxicities (grade ≥ 3), the group receiving the combined therapy had higher rates of hypertension (RR = 3.56 95 % CI: 2.58 to 4.92; p < 0.00001), proteinuria (RR = 1.89; 95 % CI: 1.26 to 2.84; p = 0.002), gastrointestinal perforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to 1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003). The combination of chemotherapy with bevacizumab increased the response rate, progression-free survival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free survival (PFS) and overall survival (OS) were comparatively higher

A Quality Improvement Initiative to Increase Colorectal Cancer (CRC) Screening: Collaboration between a Primary Care Clinic and Research Team.

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Green, Beverly B; Fuller, Sharon; Anderson, Melissa L; Mahoney, Christine; Mendy, Peter; Powell, Susan L

2017-01-01

Multiple randomized controlled trials have demonstrated that mailed fecal testing programs are effective in increasing colorectal cancer screening participation. However, few healthcare organization in the US have Implemented such programs. Stakeholders from one clinic in an integrated healthcare system in Washington State initiated collaboration with researchers with expertise in CRC screening, aiming to increase screening rates at their clinic. Age-eligible individuals who were overdue for CRC screening and had previously completed a fecal test were randomized to receive mailed fecal immunochemical test kits (FIT) at the start of the project (Early) or 6 months later (Late). Outcomes included comparing FIT completion at 6 months by randomization group, and overall CRC screening rates at 12 months. We also assessed implementation facilitators and challenges. Overall 2,421 FIT tests were mailed at a cost of $10,739. At 6 months, FIT completion was significantly higher among the Early compared to the Late group (62% vs.47%, p CRC screening rate was 75.1% at baseline and 78.0% 12 months later. Key constructs associated with successful program implementation included strong stakeholder involvement, use of evidence-based strategies, simplicity, and low cost. Challenges included lack of a plan for maintaining the program. Collaboration between clinic stakeholders and researchers led to a successful project that rapidly increased CRC screening rates. However, institutional normalization of the program would be required to maintain it.

Diabetes mellitus type 2 and subsite-specific colorectal cancer risk in men and women: results from the Netherlands Cohort Study on diet and cancer.

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de Kort, Sander; Simons, C C J M; van den Brandt, Piet A; Goldbohm, R Alexandra Sandra; Arts, Ilja C W; de Bruine, Adriaan P; Janssen-Heijnen, Maryska L G; Sanduleanu, Silvia; Masclee, Ad A M; Weijenberg, Matty P

2016-08-01

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer (CRC); however, studies differentiating between subsites of CRC are limited. We investigated how diabetes mellitus (DM) was associated with subsite-specific CRC risk in men and women. The Netherlands Cohort Study on diet and cancer is a prospective study among 120 852 men and women aged 55-69 years old at baseline in 1986. Information on DM, anthropometric, dietary and lifestyle factors was self-reported at baseline. T2DM was defined as the diagnosis of DM after 30 years of age. Incident CRC cases were identified by record linkage with the Netherlands cancer registry and the Dutch pathology registry. After 17.3 years of follow-up, 1735 incident male CRC cases and 1321 female CRC cases were available for analyses. Subsite-specific hazard ratios (HRs) for CRC were estimated in case-cohort analyses using Cox regression. At baseline, 3.1% of subcohort members reported T2DM, of whom 80% were diagnosed after 50 years of age. Multivariable-adjusted models showed that the risk of proximal colon cancer was significantly increased in women with T2DM versus women without T2DM (HR=1.80, 95% confidence interval: 1.10-2.94). There was no association between T2DM and the risk of overall CRC, distal colon cancer and rectal cancer in women. In men, T2DM was not associated with overall CRC (HR=0.98, 95% confidence interval: 0.64-1.50), or with risk at any subsite. This prospective study showed an increased risk of proximal colon cancer in women with T2DM compared with non-T2DM women.

Risk factors for colorectal cancer in subjects with family history of the disease.

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Fernandez, E; La Vecchia, C; D'Avanzo, B; Negri, E; Franceschi, S

1997-01-01

The relationship between lifestyle factors, past medical conditions, daily meal frequency, diet and the risk of 'familial' colorectal cancer has been analysed using data from a case-control study conducted in northern Italy. A total of 1584 colorectal cancer patients and 2879 control subjects were admitted to a network of hospitals in the Greater Milan area and the Pordenone province. The subjects included for analysis were the 112 cases and the 108 control subjects who reported a family history of colorectal cancer in first-degree relatives. Colorectal cancer cases and control subjects with family history were similarly distributed according to sex, age, marital status, years of schooling and social class. Familial colorectal cancer was associated with meal frequency, medical history of diabetes (relative risk, RR = 4.6) and cholelithiasis (RR = 5.2). Significant positive trends of increasing risk with more frequent consumption were observed for pasta (RR = 2.5, for the highest vs the lowest intake tertile), pastries (RR = 2.4), red meat (RR = 2.9), canned meat (RR = 1.9), cheese (RR = 3.5) and butter (RR = 1.9). Significant inverse associations and trends in risk were observed for consumption of poultry (RR = 0.4), tomatoes (RR = 0.2), peppers (RR = 0.3) and lettuce (RR = 0.3). Significant inverse trends in risk with increasing consumption for beta-carotene and ascorbic acid were observed (RR = 0.5 and 0.4 respectively, highest vs lowest intake tertile). These results suggest that risk factors for subjects with a family history of colorectal cancer in first-degree relatives are not appreciably different from recognized risk factors of the disease in the general population.

Barriers to CRC Screening among Latino Adults in Pennsylvania: ACCN Results

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Garcia-Dominic, Oralia; Lengerich, Eugene J.; Wray, Linda A.; Parrott, Roxanne; Aumiller, Betsy; Kluhsman, Brenda; Renderos, Carlos; Dignan, Mark

2012-01-01

Objectives: To describe knowledge of and barriers to colorectal cancer (CRC) screening by sex and geography among Latino adults in Pennsylvania. Methods: Eighty-two Latinos greater than 50 years old engaged in one of 8 focus groups. Focus groups consisted of 4 components. Focus group data were audiotaped, transcribed, and grouped into thematic…

Hereditary Colorectal Cancer (CRC Program in Latvia

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Irmejs Arvids

2003-12-01

Full Text Available Abstract Introduction The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35% pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC and 15 cases (1.73% were suspected of HNPCC. In 69 cases (8% with a cancer family aggregation (CFA were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.

Dietary patterns and colorectal cancer risk in a Korean population

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Park, Yoon; Lee, Jeonghee; Oh, Jae Hwan; Shin, Aesun; Kim, Jeongseon

2016-01-01

Abstract Colorectal cancer (CRC) has been recognized as one of the major malignancies in Korea. Analyses of dietary patterns can provide insight into the complex interactions of foods, nutrients, and biologically active components within a diet, which vary among populations. We aimed to investigate the associations between dietary patterns and colorectal cancer risk in Koreans. In a study of 923 cases and 1846 controls, principal component analysis was used to identify dietary patterns based on 33 predefined food groups using a 106-item semiquantitative food frequency questionnaire (SQFFQ). The associations between dietary patterns and CRC risk were assessed using binary and polytomous logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Three dietary patterns (traditional, Westernized, and prudent) were derived. The proportion of total variation explained by 3 patterns was 24.2% for men and 25.3% for women. The traditional and prudent patterns were inversely associated with CRC risk [OR and 95% CI for the highest intake tertile of pattern score vs. the lowest = 0.35 (0.27–0.46) and 0.37 (0.28–0.48), respectively], whereas the Westernized pattern showed a positive association, especially among women [OR = 2.13 (1.35–3.34) for the highest tertile vs. the lowest]. A decrease in CRC risk among those with the highest intake of the prudent pattern was observed in all anatomical subsites in both men [OR = 0.36 (0.19–0.68) for proximal colon; 0.21 (0.12–0.36) for distal colon; 0.28 (0.18–0.44) for rectum] and women [OR = 0.28 (0.11–0.71); 0.27 (0.13–0.54); 0.45 (0.25–0.83)]. Our results indicate that individuals who prefer the Westernized dietary pattern should be made aware of their increased CRC risk. The traditional dietary pattern and the prudent pattern, which are rich in fruits and dairy products, are recommended for the Korean population to prevent CRC. PMID:27336862

Cumulative Small Effect Genetic Markers and the Risk of Colorectal Cancer in Poland, Estonia, Lithuania, and Latvia

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Pablo Serrano-Fernandez

2015-01-01

Full Text Available The continued identification of new low-penetrance genetic variants for colorectal cancer (CRC raises the question of their potential cumulative effect among compound carriers. We focused on 6 SNPs (rs380284, rs4464148, rs4779584, rs4939827, rs6983267, and rs10795668, already described as risk markers, and tested their possible independent and combined contribution to CRC predisposition. Material and Methods. DNA was collected and genotyped from 2330 unselected consecutive CRC cases and controls from Estonia (166 cases and controls, Latvia (81 cases and controls, Lithuania (123 cases and controls, and Poland (795 cases and controls. Results. Beyond individual effects, the analysis revealed statistically significant linear cumulative effects for these 6 markers for all samples except of the Latvian one (corrected P value = 0.018 for the Estonian, corrected P value = 0.0034 for the Lithuanian, and corrected P value = 0.0076 for the Polish sample. Conclusions. The significant linear cumulative effects demonstrated here support the idea of using sets of low-risk markers for delimiting new groups with high-risk of CRC in clinical practice that are not carriers of the usual CRC high-risk markers.

The performance of the SEPT9 gene methylation assay and a comparison with other CRC screening tests: A meta-analysis.

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Song, Lele; Jia, Jia; Peng, Xiumei; Xiao, Wenhua; Li, Yuemin

2017-06-08

The SEPT9 gene methylation assay is the first FDA-approved blood assay for colorectal cancer (CRC) screening. Fecal immunochemical test (FIT), FIT-DNA test and CEA assay are also in vitro diagnostic (IVD) tests used in CRC screening. This meta-analysis aims to review the SEPT9 assay performance and compare it with other IVD CRC screening tests. By searching the Ovid MEDLINE, EMBASE, CBMdisc and CJFD database, 25 out of 180 studies were identified to report the SEPT9 assay performance. 2613 CRC cases and 6030 controls were included, and sensitivity and specificity were used to evaluate its performance at various algorithms. 1/3 algorithm exhibited the best sensitivity while 2/3 and 1/1 algorithm exhibited the best balance between sensitivity and specificity. The performance of the blood SEPT9 assay is superior to that of the serum protein markers and the FIT test in symptomatic population, while appeared to be less potent than FIT and FIT-DNA tests in asymptomatic population. In conclusion, 1/3 algorithm is recommended for CRC screening, and 2/3 or 1/1 algorithms are suitable for early detection for diagnostic purpose. The SEPT9 assay exhibited better performance in symptomatic population than in asymptomatic population.

Motoric Cognitive Risk Syndrome and Falls Risk: A Multi-Center Study

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Callisaya, Michele L.; Ayers, Emmeline; Barzilai, Nir; Ferrucci, Luigi; Guralnik, Jack M.; Lipton, Richard B.; Otahal, Petr; Srikanth, Velandai K.; Verghese, Joe

2016-01-01

Background The Motoric Cognitive Risk Syndrome (MCR) is characterized by slow gait speed and cognitive complaints. Objectives The objective of this study was to determine if the presence of MCR increases the risk of falls in older people. Methods Individual participant data (n = 6,204) from five longitudinal studies from three countries were used for this analysis. MCR diagnosis was defined as both the presence of objectively measured slow gait speed and subjective cognitive complaints in those without dementia or mobility disability. Falls were prospectively ascertained using phone calls or questionnaires. Log binomial regression was performed to determine if MCR increased the risk of falls separately in each cohort. Random effects meta-analysis was used to pool results from all cohorts. Results The mean age of participants was 74.9 (SD 6.8) years and 44% (n = 2728) were male. Overall 33.9% (n = 2104) reported a fall over follow-up. Pooled relative risk of MCR with any falls was RR 1.44 95% CI 1.16, 1.79. The components of MCR, slow gait (RR 1.30 95% CI 1.14, 1.47) and cognitive complaint (RR 1.25, 95% CI 1.07, 1.46) were also associated with an increased risk of any falls. In sub-analyses MCR was associated with any fall independent of previous falls (RR 1.29 95% CI 1.09, 1.53) and with multiple falls (RR 1.77, 95% CI 1.25, 2.51). Conclusion MCR is associated with an increased risk of falls. The increase in risk was higher than for its individual components. The simplicity of the MCR makes it an attractive falls risk screening tool for the clinic. PMID:27340851

29 CFR 37.64 - What procedures must the Director follow when CRC has completed a post-approval compliance review?

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true What procedures must the Director follow when CRC has completed a post-approval compliance review? 37.64 Section 37.64 Labor Office of the Secretary of Labor... (WIA) Compliance Procedures § 37.64 What procedures must the Director follow when CRC has completed a...

Millimeter-wave spectroscopy of CrC (X(3)Σ(-)) and CrCCH (X̃ (6)Σ(+)): Examining the chromium-carbon bond.

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Min, J; Ziurys, L M

2016-05-14

Pure rotational spectroscopy of the CrC (X(3)Σ(-)) and CrCCH (X̃ (6)Σ(+)) radicals has been conducted using millimeter/sub-millimeter direct absorption methods in the frequency range 225-585 GHz. These species were created in an AC discharge of Cr(CO)6 and either methane or acetylene, diluted in argon. Spectra of the CrCCD were also recorded for the first time using deuterated acetylene as the carbon precursor. Seven rotational transitions of CrC were measured, each consisting of three widely spaced, fine structure components, arising from spin-spin and spin-rotation interactions. Eleven rotational transitions were recorded for CrCCH and five for CrCCD; each transition in these cases was composed of a distinct fine structure sextet. These measurements confirm the respective (3)Σ(-) and (6)Σ(+) ground electronic states of these radicals, as indicated from optical studies. The data were analyzed using a Hund's case (b) Hamiltonian, and rotational, spin-spin, and spin-rotation constants have been accurately determined for all three species. The spectroscopic parameters for CrC were significantly revised from previous optical work, while those for CrCCH are in excellent agreement; completely new constants were established for CrCCD. The chromium-carbon bond length for CrC was calculated to be 1.631 Å, while that in CrCCH was found to be rCr-C = 1.993 Å - significantly longer. This result suggests that a single Cr-C bond is present in CrCCH, preserving the acetylenic structure of the ligand, while a triple bond exists in CrC. Analysis of the spin constants suggests that CrC has a nearby excited (1)Σ(+) state lying ∼16 900 cm(-1) higher in energy, and CrCCH has a (6)Π excited state with E ∼ 4800 cm(-1).

Shift work and colorectal cancer risk in the MCC-Spain case-control study.

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Papantoniou, Kyriaki; Castaño-Vinyals, Gemma; Espinosa, Ana; Turner, Michelle C; Alonso-Aguado, Maria Henar; Martin, Vicente; Aragonés, Nuria; Pérez-Gómez, Beatriz; Pozo, Benito Mirón; Gómez-Acebo, Inés; Ardanaz, Eva; Altzibar, Jone M; Peiro, Rosana; Tardon, Adonina; Lorca, José Andrés; Chirlaque, Maria Dolores; García-Palomo, Andrés; Jimenez-Moleon, Jose Juan; Ierssen, Trinidad; Ederra, Maria; Amiano, Pilar; Pollan, Marina; Moreno, Victor; Kogevinas, Manolis

2017-05-01

Objectives Shift work that involves circadian disruption has been associated with a higher cancer risk. Most epidemiological studies to date have focused on breast cancer risk and evidence for other common tumors is limited. We evaluated the risk for colorectal cancer (CRC) in relation to shift work history in a population-based case-control study in Spain. Methods This analysis included 1626 incident CRC cases and 3378 randomly selected population controls of both sexes, enrolled in 11 regions of Spain. Sociodemographic and lifestyle information was assessed in face-to-face interviews. Shift work was assessed in detail throughout lifetime occupational history. We estimated the risk of colon and rectal cancer associated with rotating and permanent shift work (ever, cumulative duration, age of first exposure) using unconditional logistic regression analysis adjusting for potential confounders. Results Having ever performed rotating shift work (morning, evening and/or night) was associated with an increased risk for CRC [odds ratio (OR) 1.22, 95% confidence interval (95% CI) 1.04-1.43], as compared to day workers. Having ever worked permanent night shifts (≥3 nights/month) was not associated with CRC risk (OR 0.79, 95% CI 0.62-1.00). OR increased with increasing lifetime cumulative duration of rotating shift work (P-value for trend 0.005) and were highest among subjects in the top quartiles of exposure (3 rd quartile, 20-34 years, OR 1.38, 95%CI 1.06-1.81; 4 th quartile, ≥35 years, OR 1.36, 95% CI 1.02-1.79). Conclusions These data suggest that rotating shift work may increase the risk of CRC especially after long-term exposures.

Backbone and stereospecific (13)C methyl Ile (δ1), Leu and Val side-chain chemical shift assignments of Crc.

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Sharma, Rakhi; Sahu, Bhubanananda; Ray, Malay K; Deshmukh, Mandar V

2015-04-01

Carbon catabolite repression (CCR) allows bacteria to selectively assimilate a preferred compound among a mixture of several potential carbon sources, thus boosting growth and economizing the cost of adaptability to variable nutrients in the environment. The RNA-binding catabolite repression control (Crc) protein acts as a global post-transcriptional regulator of CCR in Pseudomonas species. Crc triggers repression by inhibiting the expression of genes involved in transport and catabolism of non-preferred substrates, thus indirectly favoring assimilation of preferred one. We report here a nearly complete backbone and stereospecific (13)C methyl side-chain chemical shift assignments of Ile (δ1), Leu and Val of Crc (~ 31 kDa) from Pseudomonas syringae Lz4W.

Baseline dietary glutamic acid intake and the risk of colorectal cancer: The Rotterdam study.

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Viana Veloso, Gilson G; Franco, Oscar H; Ruiter, Rikje; de Keyser, Catherina E; Hofman, Albert; Stricker, Bruno C; Kiefte-de Jong, Jessica C

2016-03-15

Animal studies have shown that glutamine supplementation may decrease colon carcinogenesis, but any relation with glutamine or its precursors has not been studied in humans. The primary aim of this study was to assess whether dietary glutamic acid intake was associated with colorectal cancer (CRC) risk in community-dwelling adults. A secondary aim was to evaluate whether the association could be modified by the body mass index (BMI). This study was embedded in the Rotterdam study, which included a prospective cohort from 1990 onward that consisted of 5362 subjects who were 55 years old or older and were free of CRC at the baseline. Glutamic acid was calculated as a percentage of the total protein intake with a validated food frequency questionnaire at the baseline. Incident cases of CRC were pathology-based. During follow-up, 242 subjects developed CRC. Baseline dietary glutamic acid intake was significantly associated with a lower risk of developing CRC (hazard ratio [HR] per percent increase in glutamic acid of protein, 0.78; 95% confidence interval [CI], 0.62-0.99). After stratification for BMI, the risk reduction for CRC by dietary glutamic acid was 42% for participants with a BMI ≤ 25 kg/m(2) (HR per percent increase in glutamic acid of protein, 0.58; 95% CI, 0.40-0.85), whereas no association was found in participants with a BMI > 25 kg/m(2) (HR per percent increase in glutamic acid of protein, 0.97; 95% CI, 0.73-1.31). Our data suggest that baseline dietary glutamic acid intake is associated with a lower risk of developing CRC, but this association may be mainly present in nonoverweight subjects. © 2015 American Cancer Society.

Association between MLH1 -93G>a polymorphism and risk of colorectal cancer.

Directory of Open Access Journals (Sweden)

Ting Wang

Full Text Available The -93G>A (rs1800734 polymorphism located in the promoter of mismatch repair gene, MLH1, has been identified as a low-penetrance variant for cancer risk. Many published studies have evaluated the association between the MLH1 -93G>A polymorphism and colorectal cancer (CRC risk. However, the results remain conflicting rather than conclusive.The aim of this study was to assess the association between the MLH1 -93G>A polymorphism and the risk of CRC.To derive a more precise estimation of the association, a meta-analysis of six studies (17,791 cases and 13,782 controls was performed. Odds ratios (ORs and 95% confidence intervals (CIs were used to evaluate the strength of the association. Four of these published studies were performed on subjects of known microsatellite instability (MSI status. An additional analysis including 742 cases and 10,895 controls was used to assess the association between the MLH1 -93G>A polymorphism and the risk of MSI-CRC.The overall results indicated that the variant genotypes were associated with a significantly increased risk of CRC (AG versus GG: OR = 1.06, 95% CI = 1.01-1.11; AA/AG versus GG: OR = 1.06, 95% CI = 1.01-1.11. This increased risk was also found during stratified analysis of MSI status (AA versus GG: OR = 2.52, 95% CI = 1.94-3.28; AG versus GG: OR = 1.29, 95% CI = 1.10-1.52; AA/AG versus GG: OR = 1.45, 95% CI = 1.24-1.68; AA versusOR = 2.29, 95% CI = 1.78-2.96. Egger's test did not show any evidence of publication bias.Our results suggest that the MLH1 -93G>A polymorphism may contribute to individual susceptibility to CRC and act as a risk factor for MSI-CRC.

Lignification of the plant and seed quality of RR soybeans sprayed with herbicide glyphosate Lignificação da planta e qualidade de sementes de soja RR pulverizadas com herbicida glifosato

Directory of Open Access Journals (Sweden)

Cristiane Fortes Gris

2013-04-01

Full Text Available Differences in levels of lignin in the plant between conventional and transgenic cultivars RR has been reported by several authors, however, there are few studies evaluating the influence of spraying of glyphosate on the lignin in the plant and RR soybean seeds. The aim of this study was to evaluate the physiological quality of RR transgenic soybean seeds and the lignin contents of plants sprayed with the herbicide glyphosate. The assays were conducted both in greenhouse and field in the municipality of Lavras, MG, in the agricultural year 2007/08. The experiment was arranged in a splitplot design with four replicates, considering the treatments hand weeding and herbicide glyphosate as plots, and five RR soybean cultivars (BRS 245 RR, BRS 247 RR, Valiosa RR, Silvânia RR and Baliza RR as splitplots. In the greenhouse, the cultivars tested were BRS 245 RR and Valiosa RR in a randomized block design with four replicates. The sprayings were carried out at stages V3, V7 and early R5 (3L/ha. The 1000 seed weight, mechanical injury, germination and germination velocity index, emergence velocity index, accelerated aging, electrical conductivity and water soaking seed test, lignin content in the seed coat, in the stem and legumes were determined. The spraying of glyphosate herbicide, in greenhouse and field, did not alter the physiological quality of seeds and the lignin contents in the plant.Diferenças nos teores de lignina na planta entre cultivares transgênicos RR e convencionais, tem sido relatadas, por vários autores, no entanto, são escassos os trabalhos avaliando a influência da aplicação do glifosato sobre os teores de lignina na planta e em sementes de soja RR. Neste sentido, objetivou-se, com este trabalho, avaliar a qualidade fisiológica de sementes de soja transgênica RR e os teores de lignina de plantas submetidas à pulverização com o herbicida glifosato. Os ensaios foram conduzidos em casa de vegetação e em campo, no munic

The Crc global regulator inhibits the Pseudomonas putida pWW0 toluene/xylene assimilation pathway by repressing the translation of regulatory and structural genes.

Science.gov (United States)

Moreno, Renata; Fonseca, Pilar; Rojo, Fernando

2010-08-06

In Pseudomonas putida, the expression of the pWW0 plasmid genes for the toluene/xylene assimilation pathway (the TOL pathway) is subject to complex regulation in response to environmental and physiological signals. This includes strong inhibition via catabolite repression, elicited by the carbon sources that the cells prefer to hydrocarbons. The Crc protein, a global regulator that controls carbon flow in pseudomonads, has an important role in this inhibition. Crc is a translational repressor that regulates the TOL genes, but how it does this has remained unknown. This study reports that Crc binds to sites located at the translation initiation regions of the mRNAs coding for XylR and XylS, two specific transcription activators of the TOL genes. Unexpectedly, eight additional Crc binding sites were found overlapping the translation initiation sites of genes coding for several enzymes of the pathway, all encoded within two polycistronic mRNAs. Evidence is provided supporting the idea that these sites are functional. This implies that Crc can differentially modulate the expression of particular genes within polycistronic mRNAs. It is proposed that Crc controls TOL genes in two ways. First, Crc inhibits the translation of the XylR and XylS regulators, thereby reducing the transcription of all TOL pathway genes. Second, Crc inhibits the translation of specific structural genes of the pathway, acting mainly on proteins involved in the first steps of toluene assimilation. This ensures a rapid inhibitory response that reduces the expression of the toluene/xylene degradation proteins when preferred carbon sources become available.

Polymorphisms in NFkB, PXR, LXR and risk of colorectal cancer in a prospective study of Danes

DEFF Research Database (Denmark)

Andersen, Vibeke; Christensen, Jane; Overvad, Kim

2010-01-01

. There was no interaction between use of nonsteroid antiinflammatory drugs (NSAID) or smoking status and NFkB, PXR or LXR polymorphisms. Conclusions A polymorphism in NFkB was associated with CRC risk and there was interaction between this polymorphism and meat intake in relation to CRC risk. This study suggests a role......-B, pregnane X receptor, and liver X receptor were associated with risk of CRC, and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. Methods The polymorphisms nuclear factor kappa-B (NFkB, NFKB1) -94 insertion/deletion ATTG (rs28362491), pregnane X...... and Health study of 57,053 persons. Results Carriers of NFkB -94deletion were at 1.45-fold higher risk of CRC than homozygous carriers of the insertion allele (incidence rate ratio (IRR) = 1.45, 95% confidence interval (95% CI): 1.10-1.92). There was interaction between this polymorphism and intake of red...

Effectiveness of Colorectal Cancer Screening in Detecting Earlier-stage Disease - a Nationwide Cohort Study in Denmark

DEFF Research Database (Denmark)

Larsen, Mette Bach; Njor, Sisse; Ingeholm, Peter

2018-01-01

program (March 1, 2014 through June 30, 2015). A total of 402,826 residents of Denmark (50-72 years old) were randomly invited to undergo CRC screening within the study period and 956,514 were invited thereafter. We obtained information on CRC diagnosis, date, and stage at diagnosis from the Danish.......6/100,000 not yet invited individuals. CRC incidence increased with age among invited and not yet invited individuals. For invited women compared to not yet invited women, the RR of being diagnosed with stage I CRC was 3.39 (95% CI, 2.61-4.39); with stage II CRC was 2.16 (95% CI, 1.71-2.72); with stage III CRC...

No Association between HMOX1 and Risk of Colorectal Cancer and No Interaction with Diet and Lifestyle Factors in a Prospective Danish Case-Cohort Study

Directory of Open Access Journals (Sweden)

Vibeke Andersen

2015-01-01

Full Text Available Red meat is a risk factor for colorectal cancer (CRC. We wanted to evaluate whether a functional polymorphism in the HMOX1 gene encoding heme oxygenase modifies risk of CRC or interacts with diet or lifestyle factors because this would identify heme or heme iron as a risk factor of CRC. The HMOX1 A-413T (rs2071746 was assessed in relation to risk of colorectal cancer (CRC and interactions with diet (red meat, fish, fiber, cereals, fruit and vegetables and lifestyle (use of non-steroidal anti-inflammatory drug and smoking status were assessed in a case-cohort study of 928 CRC cases and a comparison group of 1726 randomly selected participants from a prospective study of 57,053 persons. No association between HMOX1 A-413T and CRC risk was found (TT vs. AA + TA; IRR = 1.15, 95% CI: 0.98–1.36, p = 0.10 for the adjusted estimate. No interactions were found between diet or lifestyle and HMOX1 A-413T. HMOX1 A-413T was not associated with CRC risk and no interactions with diet or lifestyle were identified in this large, prospective cohort with high meat intake. The results reproduced the previous findings from the same cohort and did not support a link between heme or heme iron and colorectal cancer. These results should be sought and replicated in other well-characterized cohorts with high meat intake.

Nitrate in drinking water and colorectal cancer risk: A nationwide population-based cohort study.

Science.gov (United States)

Schullehner, Jörg; Hansen, Birgitte; Thygesen, Malene; Pedersen, Carsten B; Sigsgaard, Torben

2018-07-01

Nitrate in drinking water may increase risk of colorectal cancer due to endogenous transformation into carcinogenic N-nitroso compounds. Epidemiological studies are few and often challenged by their limited ability of estimating long-term exposure on a detailed individual level. We exploited population-based health register data, linked in time and space with longitudinal drinking water quality data, on an individual level to study the association between long-term drinking water nitrate exposure and colorectal cancer (CRC) risk. Individual nitrate exposure was calculated for 2.7 million adults based on drinking water quality analyses at public waterworks and private wells between 1978 and 2011. For the main analyses, 1.7 million individuals with highest exposure assessment quality were included. Follow-up started at age 35. We identified 5,944 incident CRC cases during 23 million person-years at risk. We used Cox proportional hazards models to estimate hazard ratios (HRs) of nitrate exposure on the risk of CRC, colon and rectal cancer. Persons exposed to the highest level of drinking water nitrate had an HR of 1.16 (95% CI: 1.08-1.25) for CRC compared with persons exposed to the lowest level. We found statistically significant increased risks at drinking water levels above 3.87 mg/L, well below the current drinking water standard of 50 mg/L. Our results add to the existing evidence suggesting increased CRC risk at drinking water nitrate concentrations below the current drinking water standard. A discussion on the adequacy of the drinking water standard in regards to chronic effects is warranted. © 2018 UICC.

CARING (CAncer Risk and INsulin analoGues): the association of diabetes mellitus and cancer risk with focus on possible determinants - a systematic review and a meta-analysis.

Science.gov (United States)

Starup-Linde, Jakob; Karlstad, Oystein; Eriksen, Stine Aistrup; Vestergaard, Peter; Bronsveld, Heleen K; de Vries, Frank; Andersen, Morten; Auvinen, Anssi; Haukka, Jari; Hjellvik, Vidar; Bazelier, Marloes T; Boer, Anthonius de; Furu, Kari; De Bruin, Marie L

2013-11-01

Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se. To examine the association between DM and cancers by a systematic review and meta-analysis according to the PRISMA guidelines. The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: "Diabetes mellitus", "Neoplasms", and "Risk of cancer". The included studies compared the risk of cancer in diabetic patients versus non-diabetic patients. All types of observational study designs were included. Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer. Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index, and possible effect modification of age, gender, with some influence of study characteristics (population source, cancer- and diabetes ascertainment). Publication bias seemed to be present. Only published data were used in the analyses. The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes patients are at an increased risk of cancer.

SNP rs16906252C>T is an expression and methylation quantitative trait locus associated with an increased risk of developing MGMT-methylated colorectal cancer

Science.gov (United States)

Kuroiwa-Trzmielina, Joice; Wang, Fan; Rapkins, Robert W.; Ward, Robyn L.; Buchanan, Daniel D.; Win, Aung Ko; Clendenning, Mark; Rosty, Christophe; Southey, Melissa C.; Winship, Ingrid M.; Hopper, John L.; Jenkins, Mark A.; Olivier, Jake; Hawkins, Nicholas J.; Hitchins, Megan P.

2016-01-01

Purpose Methylation of the MGMT promoter is the major cause of O6-methylguanine methyltransferase deficiency in cancer and has been associated with the T variant of the promoter-enhancer SNP rs16906252C>T. We sought evidence for an association between the rs16906252C>T genotype and increased risk of developing a subtype of colorectal cancer (CRC) featuring MGMT methylation, mediated by genotype-dependent epigenetic silencing within normal tissues. Experimental design By applying a molecular pathological epidemiology case-control study design, associations between rs16906252C>T and risk for CRC overall, and CRC stratified by MGMT methylation status, were estimated using multinomial logistic regression in two independent retrospective series of CRC cases and controls. The test sample comprised 1054 CRC cases and 451 controls from Sydney, Australia. The validation sample comprised 612 CRC cases and 245 controls from the Australasian Colon Cancer Family Registry (ACCFR). To determine if rs16906252C>T was linked to a constitutively altered epigenetic state, quantitative allelic expression and methylation analyses were performed in normal tissues. Results An association between rs16906252C>T and increased risk of developing MGMT-methylated CRC in the Sydney sample was observed (OR 3.3; 95%CI=2.0–5.3; PT represents an expression and methylation quantitative trait locus. Conclusions We provide evidence that rs16906252C>T is associated with elevated risk for MGMT-methylated CRC, likely mediated by constitutive epigenetic repression of the T allele. PMID:27267851

Macronutrients intake and risk of Parkinson's disease: A meta-analysis.

Science.gov (United States)

Wang, Aimin; Lin, Yan; Wu, Yili; Zhang, Dongfeng

2015-05-01

We carried out a meta-analysis to summarize the evidence from published studies on macronutrients intake and risk of Parkinson's disease (PD). Pertinent studies were identified by a search of PubMed and Embase. Study-specific effect was combined with the random-effect model. The dose-response relationship was assessed by the restricted cubic spline. For highest versus lowest level of intake, the relative risk (RR) of PD was 1.13 (95% CI 0.88-1.44) for protein (7 articles including 1570 PD cases among 357,827 subjects), RR 1.24 (95% CI 1.05-1.48) for carbohydrate (8 articles including 1482 PD cases among 232,869 subjects), RR 0.88 (95% CI 0.74-1.06) for fat (12 articles including 2936 PD cases among 374,124 subjects), RR 0.97 (95% CI 0.75-1.26) for cholesterol (6 articles including 1713 PD cases among 170,058 subjects) and 1.39 (95% CI 1.01-1.92) for energy (8 articles including 1553 PD cases among 170,317 subjects), respectively. Among prospective studies adjusting for smoking and coffee/caffeine, no associations were found between PD risk and intake of protein (RR 1.02, 95% CI 0.80-1.30), carbohydrate (RR 1.11, 95% CI 0.86-1.43), fat (RR 0.90, 95% CI 0.70-1.16), cholesterol (RR 0.89, 95% CI 0.74-1.09) and energy (RR 0.97, 95% CI 0.93-1.02); however, polyunsaturated fatty acid (RR 0.78, 95% CI 0.64-0.96) was inversely associated with PD risk. Limited data showed a linear dose-response relationship between the aforementioned macronutrients and PD risk. Dietary intake of protein, carbohydrate, cholesterol and energy might be not independently associated with PD risk. Higher intake of polyunsaturated fatty acid might be inversely associated with PD risk. Confounding by smoking and coffee/caffeine should be considered regarding the association between fat intake and PD risk in further studies. © 2014 Japan Geriatrics Society.

Analysis of competing risk parameters in irradiated prostate cancer patients

International Nuclear Information System (INIS)

Mayer, R.; Mayer, E.; Langsenlehner, U.; Hackl, A.; Pummer, K.; Quehenberger, F.; Feigl, G.

2003-01-01

Purpose: Retrospective competing risk analysis of prognostic factors in definitive-irradiated prostate cancer patients. Patients and Methods: Data of 652 patients were analyzed according to three age subgroups ( 75 years; Table 1). Pre-RT PSA values (median 13.4 ng/ml) were available for 340 patients. Adjuvant hormone therapy (n = 261) consisted either of orchiectomy (n = 151) or LHRH agonist with/without antiandrogen therapy or, in the early years, diethystilbestrol. Neoadjuvant hormone therapy (n = 31) using LHRH agonists was given 6 months before and during radiotherapy. Results: Biochemical failure was observed in 69/.340 patients, 5 years after biochemical failure, 64.9% of them also had failed clinically. The cumulative incidence of local failure (LF) and distant metastases (DM) was 9.4% and 37.2%, respectively; LF and DM at the same time were seen in 18.2%. On multivariate analysis (Tables 2 and 3), advanced stage (relative risk [RR] 4.54), pre-RT PSA > 20 ng/ml (RR 2.79) and poorly differentiated tumors (RR 2.96) were significant predictors of biochemical failure. Advanced stage increased the risk of LF (RR 2.18), DM (RR 3.66), and prostate cancer death (PCD; RR 4.30). Hormone therapy decreased the risk of biochemical failure (RR 0.67), DM (RR 0.59), and PCD (RR 0.60) without reaching statistical significance. Median follow-up was 7.6 years. Conclusion: Risk of biochemical failure was predicted by pre-RT PSA, stage, and grade; in patients with biochemical failure, the cumulative incidence of death from intercurrent diseases and PCD was 25.0% and 29.2% after 5 years, respectively. The risk of DM and PCD was predicted by stage and grade. Higher age (> 75 years) decreased the relative risk of LF, DM, and PCD significantly. (orig.)

Increased risk of intestinal cancer in Crohn's disease: A meta-analysis of population-based cohort studies

DEFF Research Database (Denmark)

Jess, Tine; Gamborg, Michael; Matzen, Peter

2005-01-01

the inclusion criteria and reported SIRs of colorectal cancer (CRC) in CD varying from 0.9 to 2.2. The pooled SIR for CRC was significantly increased (SIR, 1.9; 95% CI 1.4-2.5), as was the risk for colon cancer separately (SIR, 2.5; 95% CI 1.7-3.5). Regarding small bowel cancer, five studies reported SIRs...... ranging from 3.4 to 66.7, and the overall pooled estimate was 27.1 (95% CI 14.9-49.2). CONCLUSIONS: The present meta-analysis of intestinal cancer risk in CD, based on population-based studies only, revealed an overall increased risk of both CRC and small bowel cancer among patients with CD. However, some...

CARING (CAncer Risk and INsulin analoGues): The Association of Diabetes Mellitus and Cancer Risk with Focus on Possible Determinants - A Systematic Review and a Meta-Analysis

Science.gov (United States)

Starup-Linde, Jakob; Karlstad, Øystein; Eriksen, Stine Aistrup; Vestergaard, Peter; Bronsveld, Heleen K.; de Vries, Frank; Andersen, Morten; Auvinen, Anssi; Haukka, Jari; Hjellvik, Vidar; Bazelier, Marloes T.; de Boer, Anthonius; Furu, Kari; De Bruin, Marie L.

2013-01-01

Background: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se. Objective: To examine the association between DM and cancers by a systematic review and meta-analysis according to the PRISMA guidelines. Data Sources: The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: “Diabetes mellitus”, “Neoplasms”, and “Risk of cancer”. Study Eligibility Criteria: The included studies compared the risk of cancer in diabetic patients versus non-diabetic patients. All types of observational study designs were included. Results: Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer. Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index, and possible effect modification of age, gender, with some influence of study characteristics (population source, cancer- and diabetes ascertainment). Limitations: Publication bias seemed to be present. Only published data were used in the analyses. Conclusions: The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes patients are at an increased risk of cancer. PMID:24215312

Red meat intake, NAT2, and risk of colorectal cancer: A pooled analysis of 11 studies

Science.gov (United States)

Ananthakrishnan, Ashwin N.; Du, Mengmeng; Berndt, Sonja I.; Brenner, Hermann; Caan, Bette J.; Casey, Graham; Chang-Claude, Jenny; Duggan, David; Fuchs, Charles S.; Gallinger, Steven; Giovannucci, Edward L.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hou, Lifang; Hsu, Li; Jenkins, Mark A.; Kraft, Peter; Ma, Jing; Nan, Hongmei; Newcomb, Polly A.; Ogino, Shuji; Potter, John D.; Seminara, Daniela; Slattery, Martha L.; Thornquist, Mark; White, Emily; Wu, Kana; Peters, Ulrike; Chan, Andrew T.

2014-01-01

Background Red meat intake has been associated with risk of colorectal cancer (CRC), potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and CRC has been inconsistently reported. Methods We used pooled individual-level data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models. Results From 11 studies, 8,290 CRC cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of CRC compared to the lowest quartile (OR 1.41, 95%CI 1.29 – 1.55). However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with CRC in those with a rapid/intermediate NAT2 genotype (OR 1.38, 95%CI 1.20 – 1.59) as with a slow genotype (OR 1.43, 95%CI 1.28 – 1.61) (p- interaction=0.9). Conclusion We found that high red meat intake was associated with increased risk of CRC only from retrospective case-control studies and not modified by NAT2 enzyme activity. Impact Our results suggest no interaction between NAT2 genotype and red-meat intake in mediating risk of CRC. PMID:25342387

RR Tel: Getting Under the Flux Limit: An Observation with FUSE

Science.gov (United States)

Sonnenborn, George (Technical Monitor); Kenyon, Scott J.

2004-01-01

The goal of this program is to acquire a FUSE spectrum of the symbiotic binary RR Tel. With these data, we plan to derive improved constraints on the hot component, the nebula, and perhaps the red giant wind. Based on results from AG Dra, we should also be able to use some line detections to improve atomic parameters for high ionization emission lines. This results would benefit the general FUSE community. As of this writing, the FUSE observation of RR Tel has not been made. Because RR Tel is a very bright UV source, the FUSE team is assessing the likelihood that RR Tel will have an adverse affect on the instrument.

Gauging the Galactic thick disk with RR Lyrae stars

Directory of Open Access Journals (Sweden)

Cruz G.

2012-02-01

Full Text Available In this contribution we present results from the QUEST RR Lyrae Survey of the thick disk. The survey spans ~480 sq. deg. at low latitude |b| < 30°, with multi-epoch VRI observations, obtained with the QUEST-I camera at the 1m Jürgen Stock Schmidt telescope located at the National Astronomical Observatory of Venezuela. This constitutes the first deep RR Lyrae survey of the Galactic thick disk conducted at low galactic latitudes, covering simultaneously a large range in radial (8RR Lyrae stars having accurate distances (errors <7% and individual reddenings derived from each star’s color curve at minimum light. Moreover, the use of RR Lyrae stars as tracers ensures negligible contamination from the Galactic thin disk. We find a thick disk mean scale height hZ = 0.94 ± 0.11kpc and scale length hR = 3.2 ± 0.4kpc, derived from the vertical and radial mean density profiles of RR Lyrae stars. We also find evidence of thick disk flaring and results that may suggest the thick disk radial density profile shows signs of antitruncation. We discuss our findings in the context of recent thick disk formation models.

The Interaction between Dietary Fiber and Fat and Risk of Colorectal Cancer in the Women’s Health Initiative

Directory of Open Access Journals (Sweden)

Sandi L. Navarro

2016-11-01

Full Text Available Combined intakes of specific dietary fiber and fat subtypes protect against colon cancer in animal models. We evaluated associations between self-reported individual and combinations of fiber (insoluble, soluble, and pectins, specifically and fat (omega-6, omega-3, and docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA, specifically and colorectal cancer (CRC risk in the Women’s Health Initiative prospective cohort (n = 134,017. During a mean 11.7 years (1993–2010, 1952 incident CRC cases were identified. Cox regression models computed multivariate adjusted hazard ratios to estimate the association between dietary factors and CRC risk. Assessing fiber and fat individually, there was a modest trend for lower CRC risk with increasing intakes of total and insoluble fiber (p-trend 0.09 and 0.08. An interaction (p = 0.01 was observed between soluble fiber and DHA + EPA, with protective effects of DHA + EPA with lower intakes of soluble fiber and an attenuation at higher intakes, however this association was no longer significant after correction for multiple testing. These results suggest a modest protective effect of higher fiber intake on CRC risk, but not in combination with dietary fat subtypes. Given the robust results in preclinical models and mixed results in observational studies, controlled dietary interventions with standardized intakes are needed to better understand the interaction of specific fat and fiber subtypes on colon biology and ultimately CRC susceptibility in humans.

NESDIS Blended Rain Rate (RR) Products

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The blended Rain Rate (RR) product is derived from multiple sensors/satellites. The blended products were merged from polar-orbiting and geostationary satellite...

Lignification of the plant and seed quality of RR soybeans sprayed with herbicide glyphosate

Directory of Open Access Journals (Sweden)

Cristiane Fortes Gris

2013-04-01

Full Text Available Differences in levels of lignin in the plant between conventional and transgenic cultivars RR has been reported by several authors, however, there are few studies evaluating the influence of spraying of glyphosate on the lignin in the plant and RR soybean seeds. The aim of this study was to evaluate the physiological quality of RR transgenic soybean seeds and the lignin contents of plants sprayed with the herbicide glyphosate. The assays were conducted both in greenhouse and field in the municipality of Lavras, MG, in the agricultural year 2007/08. The experiment was arranged in a splitplot design with four replicates, considering the treatments hand weeding and herbicide glyphosate as plots, and five RR soybean cultivars (BRS 245 RR, BRS 247 RR, Valiosa RR, Silvânia RR and Baliza RR as splitplots. In the greenhouse, the cultivars tested were BRS 245 RR and Valiosa RR in a randomized block design with four replicates. The sprayings were carried out at stages V3, V7 and early R5 (3L/ha. The 1000 seed weight, mechanical injury, germination and germination velocity index, emergence velocity index, accelerated aging, electrical conductivity and water soaking seed test, lignin content in the seed coat, in the stem and legumes were determined. The spraying of glyphosate herbicide, in greenhouse and field, did not alter the physiological quality of seeds and the lignin contents in the plant.

Studying RR Lyrae Stars in M4 with K2

Science.gov (United States)

Kuehn, Charles A.; Drury, Jason; Moskalik, Pawel

2017-01-01

Observations by Kepler/K2 have revolutionized the study of RR Lyrae stars by allowing the detection of new phenomena, such as low amplitude additional modes and period doubling, which had not previously been seen from the ground. During its campaign 2, K2 observed the globular cluster M4, providing the first opportunity to study a sizeable group of RR Lyrae stars that belong to a single population; the other RR Lyrae stars that have been observed from space are field stars in the galactic halo and thus belong to an assortment of populations. We present the results of our study of the RR Lyrae variables in M4 from K2 photometry. We have identified additional, low amplitude pulsation modes in the two observed RRc stars. In three RRab stars we have found the Blazhko effect with periods of 16.6 days, 22.4 days, and 44.5 days.

Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer.

Science.gov (United States)

Lawler, Mark; Alsina, Deborah; Adams, Richard A; Anderson, Annie S; Brown, Gina; Fearnhead, Nicola S; Fenwick, Stephen W; Halloran, Stephen P; Hochhauser, Daniel; Hull, Mark A; Koelzer, Viktor H; McNair, Angus G K; Monahan, Kevin J; Näthke, Inke; Norton, Christine; Novelli, Marco R; Steele, Robert J C; Thomas, Anne L; Wilde, Lisa M; Wilson, Richard H; Tomlinson, Ian

2018-01-01

Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes. RG analysis was conducted by a multidisciplinary panel of patients, clinicians and researchers (n=71). Eight working groups (WG) were constituted: discovery science; risk; prevention; early diagnosis and screening; pathology; curative treatment; stage IV disease; and living with and beyond CRC. A series of discussions led to development of draft papers by each WG, which were evaluated by a 20-strong patient panel. A final list of RGs and research recommendations (RR) was endorsed by all participants. Fifteen critical RGs are summarised below: RG1 : Lack of realistic models that recapitulate tumour/tumour micro/macroenvironment; RG2 : Insufficient evidence on precise contributions of genetic/environmental/lifestyle factors to CRC risk; RG3 : Pressing need for prevention trials; RG4 : Lack of integration of different prevention approaches; RG5 : Lack of optimal strategies for CRC screening; RG6 : Lack of effective triage systems for invasive investigations; RG7 : Imprecise pathological assessment of CRC; RG8 : Lack of qualified personnel in genomics, data sciences and digital pathology; RG9 : Inadequate assessment/communication of risk, benefit and uncertainty of treatment choices; RG10 : Need for novel technologies/interventions to improve curative outcomes; RG11 : Lack of approaches that recognise molecular interplay between metastasising tumours and their microenvironment; RG12 : Lack of reliable biomarkers to guide stage IV treatment; RG13 : Need to increase understanding of health related quality of life (HRQOL) and promote residual symptom resolution; RG14 : Lack of coordination of CRC research/funding; RG15 : Lack of effective communication between relevant stakeholders. Prioritising research activity and funding could have a significant impact on reducing CRC disease burden over

Quality control of the NPL-CRC secondary standard system used for activimeters calibration at IPEN, Sao Paulo, Brazil;Ccontrole de qualidade do sistema padrao secundario NPL-CRC utilizado na calibracao de ativimetros no IPEN

Energy Technology Data Exchange (ETDEWEB)

Martins, Elaine W.; Potiens, Maria da P.A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2009-07-01

The objective of this study was to establish a quality control program to be applied at the NPL-CRC activimeter secondary standard system, used as reference to comparison in tests made with the work tertiary standard activimeter, Capintec basic CRC{sup R}-15BT, both belonging to the Calibration Laboratory of IPEN. The repeatability, reproducibility and the precision tests were performed using a sealed check source of {sup 133}Ba, from Amersham. It was made 70 series of 10 measurements to each activimeter, totaling 1400 measurements. Considering the variation limit of 5% to precision and reproducibility tests in the nuclear medicine services, recommended by the Brazilian standard CNEN-NN-3.05, the results observed in the behavior of the IPEN activimeter were satisfactory. (author)

Risk of colorectal cancer and small bowel adenocarcinoma in Crohn's disease: a population-based study from western Hungary 1977-2008.

Science.gov (United States)

Lakatos, Peter Laszlo; David, Gyula; Pandur, Tunde; Erdelyi, Zsuzsanna; Mester, Gabor; Balogh, Mihaly; Szipocs, Istvan; Molnar, Csaba; Komaromi, Erzsebet; Kiss, Lajos S; Lakatos, Laszlo

2011-04-01

Limited data are available on the incidence and predictors of colorectal (CRC) and small bowel adenocarcinoma (SBA) in patients with Crohn's disease (CD) from population-based cohorts. Since data are completely missing from Eastern Europe, our aim was to analyze the incidence and risk factors of CD associated CRC and SBA in the population-based, Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008. The data of 506 incident CD patients were analyzed (age-at-diagnosis: 31.5, SD: 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. CRC was diagnosed in five patients (5/5758 person-year-duration) during follow-up, while no patients developed SBA in this cohort. Standardized incidence ratio (SIR) of CRC was not increased overall with five cases observed vs. 5.02 expected (SIR: 0.99, 95% CI: 0.41-2.39); however, there was a tendency for increased incidence in males (five cases observed vs. 2.56 expected; SIR: 1.95, 95% CI: 0.81-4.70). Age at onset of CD (p<0.001), male gender (p=0.022) and stenosing disease behavior at diagnosis (p<0.001) but not disease location were identified as risk factors for developing CRC in univariate analysis and Kaplan-Meier analysis. The cumulative risk for developing CRC after a disease duration of 20 years was 1.1% (95% CI: 0.6-1.7%). The incidence of CRC and SBA was not increased in this population-based CD cohort. Age at onset of CD, male gender and stenosing disease behavior at diagnosis were identified as risk factors of CRC. Copyright © 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients.

Science.gov (United States)

Tsoi, H; Lam, K C; Dong, Y; Zhang, X; Lee, C K; Zhang, J; Ng, S C; Ng, S S M; Zheng, S; Chen, Y; Fang, J; Yu, J

2017-11-02

One characteristic of cancer cells is the abnormally high rate of cell metabolism to sustain their enhanced proliferation. However, the behind mechanism of this phenomenon is still elusive. Here we find that enhanced precursor 45s ribosomal RNA (pre-45s rRNA) is one of the core mechanisms in promoting the pathogenesis of colorectal cancer (CRC). Pre-45s rRNA expression is significantly higher in primary CRC tumor tissues samples and cancer cell lines compared with the non-tumorous colon tissues, and is associated with tumor sizes. Knockdown of pre-45s rRNA inhibits G1/S cell-cycle transition by stabilizing p53 through inducing murine double minute 2 (MDM2) and ribosomal protein L11 (RpL11) interaction. In addition, we revealed that high rate of cancer cell metabolism triggers the passive release of calcium ion from endoplasmic reticulum to the cytoplasm. The elevated calcium ion in the cytoplasm activates the signaling cascade of calcium/calmodulin-dependent protein kinase II, ribosomal S6 kinase (S6K) and ribosomal S6K (CaMKII-S6K-UBF). The activated UBF promotes the transcription of rDNA, which therefore increases pre-45s rRNA. Disruption of CaMKII-S6K-UBF axis by either RNAi or pharmaceutical approaches leads to reduction of pre-45s rRNA expression, which subsequently suppresses cell proliferation in colon cancer cells by causing cell-cycle arrest. Knockdown of APC activates CaMKII-S6K-UBF cascade and thus enhances pre-45s rRNA expression. Moreover, the high expression level of pre-45s rRNA is associated with poor survival of CRC patients in two independent cohorts. Our study identifies a novel mechanism in CRC pathogenesis mediated by pre-45s rRNA and a prognostic factor of pre-45s rRNA in CRC patients.

The New UN CRC General Comment 13: "The Right of the Child to Freedom from All Forms of Violence"--Changing How the World Conceptualizes Child Protection

Science.gov (United States)

Svevo-Cianci, Kimberly A.; Herczog, Maria; Krappmann, Lothar; Cook, Philip

2011-01-01

The UN Committee on the Rights of the Child established CRC General Comment 13 (April 2011) to address today's unabating high rates of violence against children globally despite CRC advances. GC13 provides clear interpretations and stronger detail to supplement the legal language of CRC Article 19, intended to establish protection of children from…

CARING (CAncer Risk and INsulin analoGues)

DEFF Research Database (Denmark)

Linde, Jakob Starup; Karlstad, Oystein; Eriksen, Stine Aistrup

2013-01-01

=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index......BACKGROUND: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se. OBJECTIVE: To examine the association between DM and cancers by a systematic review and meta-analysis according...... to the PRISMA guidelines. DATA SOURCES: The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: "Diabetes mellitus", "Neoplasms", and "Risk of cancer". STUDY ELIGIBILITY CRITERIA: The included studies compared...

Folate Intake, MTHFR Polymorphisms, and the Risk of Colorectal Cancer: A Systematic Review and Meta-Analysis

International Nuclear Information System (INIS)

Kennedy, D. A.; Stern, S. J.; Matok, I.; Moretti, M. E.; Sarkar, M.; Webber, T. A.; Koren, G.; Kennedy, D. A.; Koren, G.; Stern, S. J.; Koren, G.

2012-01-01

Background. The objective was to determine whether relationships exist between the methylene-tetrahydrofolate reductase (Mthf) polymorphisms and risk of colorectal cancer (CRC) and examine whether the risk is modified by level of folate intake. Methods. MEDLINE, Embase, and SCOPUS were searched to May 2012 using the terms “folic acid,” “folate,” “colorectal cancer,” “methylenetetrahydrofolate reductase,” “MTHFR.” Observational studies were included which (1) assessed the risk of CRC for each polymorphism and/or (2) had defined levels of folate intake for each polymorphism and assessed the risk of CRC. Results. From 910 references, 67 studies met our criteria; hand searching yielded 10 studies. The summary risk estimate comparing the 677CT versus CC genotype was 1.02 (95% CI 0.95-1.10) and for 677TT versus CC was 0.88 (95% CI 0.80-0.96) both with heterogeneity. The summary risk estimates for A1298C polymorphisms suggested no reduced risk. The summary risk estimate for high versus low total folate for the 677CC genotype was 0.70 (95% CI 0.56-0.89) and the 677TT genotype 0.63 (95% CI 0.41-0.97). Conclusion. These results suggest that the 677TT genotype is associated with a reduced risk of developing CRC, under conditions of high total folate intake, and this associated risk remains reduced for both MTHFR 677 CC and TT genotypes.

Concentration of circulating miRNA-containing particles in serum enhances miRNA detection and reflects CRC tissue-related deregulations.

Science.gov (United States)

ElSharawy, Abdou; Röder, Christian; Becker, Thomas; Habermann, Jens K; Schreiber, Stefan; Rosenstiel, Philip; Kalthoff, Holger

2016-11-15

The emerging potential of miRNAs as biomarkers for cancer detection demands parallel evaluation of strategies for reliable identification of disease-related signatures from easily accessible and pertinent body compartments. Here, we addressed whether efficient concentration of circulating miRNA-carrying particles is a rationale for miRNA biomarker discovery. We systematically compared miRNA signatures in 93 RNA preparations from three serum entities (whole serum, particle-concentrated, and particle-depleted fractions) and corresponding tissue samples from patients with colorectal cancer (CRC) as a model disease. Significant differences between whole sera and particle-concentrated serum fractions of CRC patients emerged for 45 of 742 tested miRNAs. Twenty-eight of these 45 miRNAs were differentially expressed between particle-concentrated serum fractions of metastatic CRC- and healthy individuals. Over half of these candidates (15 of 28) showed deregulations only in concentrated serum fractions, but not in whole sera, compared to the respective controls.Our results also provided evidence of a consistent downregulation of miR-486 and miR-92a, and further showed a possible "strand-specific" deregulation of extracellular miRNAs in CRC. More importantly, most of the identified miRNAs in the enriched sera reflected the patterns of the corresponding tumor tissues and showed links to cancer-related inflammation. Further investigation of seven serum pools revealed a subset of potential extracellular miRNA candidates to be implicated in both neoplastic and inflammatory bowel disease.Our findings demonstrate that enrichment and sensitive detection of miRNA carriers is a promising approach to detect CRC-related pathological changes in liquid biopsies, and has potential for clinical diagnostics.

Steam in RR Telescopii and Henize 2-38

Energy Technology Data Exchange (ETDEWEB)

Allen, D A [Anglo-Australian Observatory, Epping (Australia); Beattie, D H; Lee, T J; Stewart, J M; Williams, P M

1978-03-01

Low-resolution scans in the 1.9-2.6..mu..m atmospheric window reveal steam (H/sub 2/O) and CO adsorption bands in the spectra of the symbiotic stars RR Tel and He 2-38. The steam absorption in RR Tel is particularly intense while the CO is weak, implying the presence in the system of a Mira variable seen near minimum light. In He 2-38 the steam band is weaker while the CO is stronger, as expected for a Mira seen near maximum.

Similar uptake profiles of microcystin-LR and -RR in an in vitro human intestinal model

International Nuclear Information System (INIS)

Zeller, P.; Clement, M.; Fessard, V.

2011-01-01

Highlights: → First description of in vitro cellular uptake of MCs into intestinal cells. → OATP 3A1 and OATP 4A1 are expressed in Caco-2 cell membranes. → MC-LR and MC-RR show similar uptake in Caco-2 cells. → MCs are probably excreted from Caco-2 cells by an active mechanism. -- Abstract: Microcystins (MCs) are cyclic hepatotoxins produced by various species of cyanobacteria. Their structure includes two variable amino acids (AA) leading to more than 80 MC variants. In this study, we focused on the most common variant, microcystin-LR (MC-LR), and microcystin-RR (MC-RR), a variant differing by only one AA. Despite their structural similarity, MC-LR elicits higher liver toxicity than MC-RR partly due to a discrepancy in their uptake by hepatic organic anion transporters (OATP 1B1 and 1B3). However, even though ingestion is the major pathway of human exposure to MCs, intestinal absorption of MCs has been poorly addressed. Consequently, we investigated the cellular uptake of the two MC variants in the human intestinal cell line Caco-2 by immunolocalization using an anti-MC antibody. Caco-2 cells were treated for 30 min to 24 h with several concentrations (1-50 μM) of both variants. We first confirmed the localization of OATP 3A1 and 4A1 at the cell membrane of Caco-2 cells. Our study also revealed a rapid uptake of both variants in less than 1 h. The uptake profiles of the two variants did not differ in our immunostaining study neither with respect to concentration nor the time of exposure. Furthermore, we have demonstrated for the first time the nuclear localization of MC-RR and confirmed that of MC-LR. Finally, our results suggest a facilitated uptake and an active excretion of MC-LR and MC-RR in Caco-2 cells. Further investigation on the role of OATP 3A1 and 4A1 in MC uptake should be useful to clarify the mechanism of intestinal absorption of MCs and contribute in risk assessment of cyanotoxin exposure.

Long-term performance of colorectal cancer screening programmes based on the faecal immunochemical test.

Science.gov (United States)

Zorzi, Manuel; Hassan, Cesare; Capodaglio, Giulia; Fedato, Chiara; Montaguti, Adriana; Turrin, Anna; Rosano, Alberto; Monetti, Daniele; Stocco, Carmen; Baracco, Susanna; Russo, Francesca; Repici, Alessandro; Rugge, Massimo

2017-11-03

The long-term performance of colorectal cancer (CRC) screening programmes based on a 2-year faecal immunochemical test (FIT) is still unclear. In a sample of 50 to 69-year-olds repeatedly screened with the FIT (OC-Hemodia latex agglutination test; cut-off: 20 µg haemoglobin/g faeces), we examined: (1) the FIT positivity rate, the CRC and advanced adenoma detection rate and the FIT's positive predictive value (PPV) for advanced neoplasia, at each round of screening and (2) the cumulative CRC and advanced adenoma detection rate after five rounds of FIT. Over 12 years (2002-2014), 123 347 individuals were administered the FIT up to six times, and 781 CRCs and 4713 advanced adenomas were diagnosed. The CRC and advanced adenoma detection rates declined substantially from the first to the third (rate ratio (RR) 0.25, 95% CI 0.20 to 0.32) and second (RR 0.51, 95% CI 0.47 to 0.56) rounds, respectively, and then remained stable. The PPV for advanced neoplasia dropped by 18% in the second round (RR 0.82, 95% CI 0.77 to 0.89), with no further reduction thereafter due to a concomitant decline in the FIT positivity rate (RR first to sixth rounds: 0.56, 95% CI 0.53 to 0.60).The cumulative CRC and advanced adenoma detection rates over five consecutive rounds were 8.5‰ (95% CI 7.8 to 9.2), and 58.9‰ (95% CI 56.9 to 61.0), respectively. Repeated FIT significantly reduces the burden of colorectal disease while facilitating an efficient use of colonoscopy resources. The cumulative detection rate after five rounds of FIT is similar to primary screening with colonoscopy, supporting the need to account for the cumulative sensitivity of repeated FITs when evaluating the test's efficacy. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Risk Factors for Blood Transfusion With Primary Posterior Lumbar Fusion.

Science.gov (United States)

Basques, Bryce A; Anandasivam, Nidharshan S; Webb, Matthew L; Samuel, Andre M; Lukasiewicz, Adam M; Bohl, Daniel D; Grauer, Jonathan N

2015-11-01

Retrospective cohort study. To identify factors associated with blood transfusion for primary posterior lumbar fusion surgery, and to identify associations between blood transfusion and other postoperative complications. Blood transfusion is a relatively common occurrence for patients undergoing primary posterior lumbar fusion. There is limited information available describing which patients are at increased risk for blood transfusion, and the relationship between blood transfusion and short-term postoperative outcomes is poorly characterized. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients undergoing primary posterior lumbar fusion from 2011 to 2013. Multivariate analysis was used to find associations between patient characteristics and blood transfusion, along with associations between blood transfusion and postoperative outcomes. Out of 4223 patients, 704 (16.7%) had a blood transfusion. Age 60 to 69 (relative risk [RR] 1.6), age greater than equal to 70 (RR 1.7), American Society of Anesthesiologists class greater than equal to 3 (RR 1.1), female sex (RR 1.1), pulmonary disease (RR 1.2), preoperative hematocrit less than 36.0 (RR 2.0), operative time greater than equal to 310 minutes (RR 2.9), 2 levels (RR 1.6), and 3 or more levels (RR 2.1) were independently associated with blood transfusion. Interbody fusion (RR 0.9) was associated with decreased rates of blood transfusion. Receiving a blood transfusion was significantly associated with any complication (RR 1.7), sepsis (RR 2.6), return to the operating room (RR 1.7), deep surgical site infection (RR 2.6), and pulmonary embolism (RR 5.1). Blood transfusion was also associated with an increase in postoperative length of stay of 1.4 days (P risk factors for these occurrences were characterized. Strategies to minimize blood loss might be considered in these patients to avoid the associated complications. 3.

Dietary patterns and colorectal cancer risk in middle-aged adults: A large population-based prospective cohort study.

Science.gov (United States)

Shin, Sangah; Saito, Eiko; Sawada, Norie; Ishihara, Junko; Takachi, Ribeka; Nanri, Akiko; Shimazu, Taichi; Yamaji, Taiki; Iwasaki, Motoki; Sasazuki, Shizuka; Inoue, Manami; Tsugane, Shoichiro

2018-06-01

A finding between dietary pattern and cancer may provide visions beyond the assessment of individual foods or nutrients. We examined the influence of dietary pattern with colorectal cancer (CRC) among a Japanese population. A total of 93,062 subjects (43,591 men, 49,471 women) who participated in the Japan Public Health Center-based Prospective Study were followed from 1995-1998 to the end of 2012, during which 2482 cases of CRC (1514 men, 968 women) were newly identified. Dietary data was obtained from a validated food-frequency questionnaire between 1995 and 1998. Three dietary pattern was derived from principal components factor: prudent, westernized, and traditional pattern. After controlled for potential confounders, the prudent pattern showed a decreased association of CRC risk in men (HR for highest quintile vs lowest: 0.85; 95% CI: 0.72-1.00; P trend cancer (P trend cancer in women (P trend pattern showed a significant positive linear trend for colon (P trend cancer (P trend dietary pattern on the overall or any specific sites risk of CRC. A prudent dietary pattern showed an inverse association with CRC risk in men, and a westernized pattern was related with a higher risk of colon and distal cancer in women. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Prediction of paroxysmal atrial fibrillation using recurrence plot-based features of the RR-interval signal

International Nuclear Information System (INIS)

Mohebbi, Maryam; Ghassemian, Hassan

2011-01-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia and increases the risk of stroke. Predicting the onset of paroxysmal AF (PAF), based on noninvasive techniques, is clinically important and can be invaluable in order to avoid useless therapeutic intervention and to minimize risks for the patients. In this paper, we propose an effective PAF predictor which is based on the analysis of the RR-interval signal. This method consists of three steps: preprocessing, feature extraction and classification. In the first step, the QRS complexes are detected from the electrocardiogram (ECG) signal and then the RR-interval signal is extracted. In the next step, the recurrence plot (RP) of the RR-interval signal is obtained and five statistically significant features are extracted to characterize the basic patterns of the RP. These features consist of the recurrence rate, length of longest diagonal segments (L max  ), average length of the diagonal lines (L mean ), entropy, and trapping time. Recurrence quantification analysis can reveal subtle aspects of dynamics not easily appreciated by other methods and exhibits characteristic patterns which are caused by the typical dynamical behavior. In the final step, a support vector machine (SVM)-based classifier is used for PAF prediction. The performance of the proposed method in prediction of PAF episodes was evaluated using the Atrial Fibrillation Prediction Database (AFPDB) which consists of both 30 min ECG recordings that end just prior to the onset of PAF and segments at least 45 min distant from any PAF events. The obtained sensitivity, specificity, positive predictivity and negative predictivity were 97%, 100%, 100%, and 96%, respectively. The proposed methodology presents better results than other existing approaches

Randomized controlled trial of storytelling compared to a personal risk tool intervention on colorectal cancer screening in low-income patients.

Science.gov (United States)

Larkey, Linda K; McClain, Darya; Roe, Denise J; Hector, Richard D; Lopez, Ana Maria; Sillanpaa, Brian; Gonzalez, Julie

2015-01-01

Screening rates for colorectal cancer (CRC) lag for low-income, minority populations, contributing to poorer survival rates. A model of storytelling as culture-centric health promotion was tested for promoting CRC screening. A two-group parallel randomized controlled trial. Primary care, safety-net clinics. Low-income patients due for CRC screening, ages 50 to 75 years, speaking English or Spanish. Patients were exposed to either a video created from personal stories composited into a drama about "Papa" receiving CRC screening, or an instrument estimating level of personal cancer risk. Patients received a health care provider referral for CRC screening and were followed up for 3 months to document adherence. Behavioral factors related to the narrative model (identification and engagement) and theory of planned behavior. Main effects of the interventions on screening were tested, controlling for attrition factors, and demographic factor associations were assessed. Path analysis with model variables was used to test the direct effects and multiple mediator models. Main effects on CRC screening (roughly half stool-based tests, half colonoscopy) did not indicate significant differences (37% and 42% screened for storytelling and risk-based messages, respectively; n = 539; 33.6% male; 62% Hispanic). Factors positively associated with CRC screening included being female, Hispanic, married or living with a partner, speaking Spanish, having a primary care provider, lower income, and no health insurance. Engagement, working through positive attitudes toward the behavior, predicted CRC screening. A storytelling and a personalized risk-tool intervention achieved similar levels of screening among unscreened/underscreened, low-income patients. Factors usually associated with lower rates of screening (e.g., no insurance, being Hispanic) were related to more adherence. Both interventions' engagement factor facilitated positive attitudes about CRC screening associated with behavior

Failure to Redose Antibiotic Prophylaxis in Long Surgery Increases Risk of Surgical Site Infection.

Science.gov (United States)

Kasatpibal, Nongyao; Whitney, Joanne D; Dellinger, E Patchen; Nair, Bala G; Pike, Kenneth C

Antibiotic prophylaxis is a key component of the prevention of surgical site infection (SSI). Failure to manage antibiotic prophylaxis effectively may increase the risk of SSI. This study aimed to examine the effects of antibiotic prophylaxis on SSI risk. A retrospective cohort study was conducted among patients having general surgery between May 2012 and June 2015 at the University of Washington Medical Center. Peri-operative data extracted from hospital databases included patient and operation characteristics, intra-operative medication and fluid administration, and survival outcome. The effects of antibiotic prophylaxis and potential factors on SSI risk were estimated using multiple logistic regression and were expressed as risk ratios (RRs). A total of 4,078 patients were eligible for analysis. Of these, 180 had an SSI. Mortality rates within and after 30 days were 0.8% and 0.3%, respectively. Improper antibiotic redosing increased the risk of SSI (RR 4.61; 95% confidence interval [CI] 1.33-15.91). Other risk factors were in-patient status (RR 4.05; 95% CI 1.69-9.66), smoking (RR 1.63; 95% CI 1.03-2.55), emergency surgery (RR 1.97; 95% CI 1.26-3.08), colectomy (RR 3.31; 95% CI 1.19-9.23), pancreatectomy (RR 4.52; 95% CI 1.53-13.39), proctectomy (RR 5.02; 95% CI 1.72-14.67), small bowel surgery (RR 6.16; 95% CI 2.13-17.79), intra-operative blood transfusion >500 mL (RR 2.76; 95% CI 1.45-5.26), and multiple procedures (RR 1.40; 95% CI 1.01-1.95). These data demonstrate that failure to redose prophylactic antibiotic during long operations increases the risk of SSI. Strengthening a collaborative surgical quality improvement program may help to eradicate this risk.

Pilot clinical study of the effects of ginger root extract on eicosanoids in colonic mucosa of subjects at increased risk for colorectal cancer.

Science.gov (United States)

Zick, Suzanna M; Turgeon, D Kim; Ren, Jianwei; Ruffin, Mack T; Wright, Benjamin D; Sen, Ananda; Djuric, Zora; Brenner, Dean E

2015-09-01

Colorectal cancer (CRC) remains a significant cause of mortality. Inhibitors of cyclooxygenase (COX) and thus prostaglandin E2, are promising CRC preventives, but have significant toxicities. Ginger has been shown to inhibit COX, to decrease the incidence and multiplicity of adenomas, and decrease PGE2 concentrations in subjects at normal risk for CRC. This study was conducted to determine the effects of 2.0 g/d of ginger given orally on the levels of PGE2, leukotriene B4 (LTB4), 13-hydroxy-octadecadienoic acids, and 5-, 12-, & 15-hydroxyeicosatetraenoic acid, in the colonic mucosa of subjects at increased risk for CRC. We randomized 20 subjects to 2.0 g/d ginger or placebo for 28 d. At baseline and Day 28, a flexible sigmoidoscopy was used to obtain colon biopsies. A liquid chromatography mass spectrometry method was used to determine eicosanoid levels in the biopsies, and levels were expressed per amount of protein or free arachidonic acid (AA). There was a significant decrease in AA between baseline and Day 28 (P = 0.05) and significant increase in LTB4 (P = 0.04) when normalized to protein, in subjects treated with ginger versus placebo. No other changes in eicosanoids were observed. There was no difference between the groups in total adverse events (AE; P = 0.06). Ginger lacks the ability to decrease eicosanoid levels in people at increased risk for CRC. Ginger did appear to be both tolerable and safe; and could have chemopreventive effects through other mechanisms. Further investigation should focus on other markers of CRC risk in those at increased CRC risk. © 2014 Wiley Periodicals, Inc.

Colorectal cancer (CRC) monitoring by 6-monthly 18FDG-PET/CT: an open-label multicentre randomised trial.

Science.gov (United States)

Sobhani, I; Itti, E; Luciani, A; Baumgaertner, I; Layese, R; André, T; Ducreux, M; Gornet, J-M; Goujon, G; Aparicio, T; Taieb, J; Bachet, J-B; Hemery, F; Retbi, A; Mons, M; Flicoteaux, R; Rhein, B; Baron, S; Cherrak, I; Rufat, P; Le Corvoisier, P; de'Angelis, N; Natella, P-A; Maoulida, H; Tournigand, C; Durand Zaleski, I; Bastuji-Garin, S

2018-04-01

[18F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18FDG-PET/CT) has high sensitivity for detecting recurrences of colorectal cancer (CRC). Our objective was to determine whether adding routine 6-monthly 18FDG-PET/CT to our usual monitoring strategy improved patient outcomes and to assess the effect on costs. In this open-label multicentre trial, patients in remission of CRC (stage II perforated, stage III, or stage IV) after curative surgery were randomly assigned (1 : 1) to usual monitoring alone (3-monthly physical and tumour marker assays, 6-monthly liver ultrasound and chest radiograph, and 6-monthly whole-body computed tomography) or with 6-monthly 18FDG-PET/CT, for 3 years. A multidisciplinary committee reviewed each patient's data every 3 months and classified the recurrence status as yes/no/doubtful. Recurrences were treated with curative surgery alone if feasible and with chemotherapy otherwise. The primary end point was treatment failure defined as unresectable recurrence or death. Relative risks were estimated, and survival was analysed using the Kaplan-Meier method, log-rank test, and Cox models. Direct costs were compared. Of the 239 enrolled patients, 120 were in the intervention arm and 119 in the control arm. The failure rate was 29.2% (31 unresectable recurrences and 4 deaths) in the intervention group and 23.7% (27 unresectable recurrences and 1 death) in the control group (relative risk = 1.23; 95% confidence interval, 0.80-1.88; P = 0.34). The multivariate analysis also showed no significant difference (hazards ratio, 1.33; 95% confidence interval, 0.8-2.19; P = 0.27). Median time to diagnosis of unresectable recurrence (months) was significantly shorter in the intervention group [7 (3-20) versus 14.3 (7.3-27), P = 0.016]. Mean cost/patient was higher in the intervention group (18 192 ± 27 679 € versus 11 131 ± 13  €, P CRC. The control group had very close follow

Gender and plasma iron biomarkers, but not HFE gene mutations, increase the risk of colorectal cancer and polyps.

Science.gov (United States)

Castiella, Agustin; Múgica, Fernando; Zapata, Eva; Zubiaurre, Leire; Iribarren, Arantxa; de Juan, M Dolores; Alzate, Luis; Gil, Ines; Urdapilleta, Gregorio; Otazua, Pedro; Emparanza, José Ignacio

2015-09-01

A cohort study of patients included in the Basque Country colorectal cancer (CRC) screening programme was carried out to assess the risk of adenomatous polyps and CRC (P-CRC) associated with HFE gene mutations, with gender and with iron biomarkers (serum ferritin (SF), iron (Fe) and transferrin saturation index (TSI)). Among 432 included patients (mean age 59.8 years), 263 were men (60.9 %) and 169 women (39.1 %). P-CRC were identified in 221 patients (51.2 %) and no polyps (NP) in 211 patients (48.8 %). HFE mutations were identified in 43.8 % of the patients. C282Y/wt genotypic frequency was 6.8 % in the P-CRC group and 1.4 % in the NP group (p < 0.05). The allelic frequency was 3.8 versus 1.2 % (p < 0.05). For laboratory, all three iron biomarkers showed a statistically significant difference: mean Fe, 91.29 ± 34 for P-CRC and 80.81 ± 30.59 for NP group. Mean TSI for P-CRC was 24.95 ± 8.90 and 22.74 ± 8.79 for NP group. Mean SF 308.09 ± 536.32 for P-CRC and 177.55 ± 159.95 for NP group. In a multivariate logistic regression analysis, only male gender (odds ratio (OR) = 2.04, 1.29-3.22), SF (OR = 1.001, 1.0004-1.003) and Fe (OR = 1.01, 1.004-1.02) were related with the presence of CRC and adenoma. Men gender and raised serum iron biomarkers increase the risk of P-CRC.

Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different risk profiles may influence clinical management

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D. Ramsoekh (Dewkoemar); A. Wagner (Anja); M.E. van Leerdam (Monique); D. Dooijes (Dennis); C.M.J. Tops (Carli); E.W. Steyerberg (Ewout); E.J. Kuipers (Ernst)

2009-01-01

textabstractBackground: Lynch syndrome (LS) is associated with a high risk for colorectal cancer (CRC) and extracolonic malignancies, such as endometrial carcinoma (EC). The risk is dependent of the affected mismatch repair gene. The aim of the present study was to calculate the cumulative risk of

Educational level and risk of colorectal cancer in EPIC with specific reference to tumor location

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Leufkens, Anke M.; van Duijnhoven, Fränzel J. B.; Boshuizen, Hendriek C.; Siersema, Peter D.; Kunst, Anton E.; Mouw, Traci; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Morois, Sophie; Krogh, Vittorio; Tumino, Rosario; Panico, Salvatore; Polidoro, Silvia; Palli, Domenico; Kaaks, Rudolf; Teucher, Birgit; Pischon, Tobias; Trichopoulou, Antonia; Orfanos, Philippos; Goufa, Ioulia; Peeters, Petra H. M.; Skeie, Guri; Braaten, Tonje; Rodríguez, Laudina; Lujan-Barroso, Leila; Sánchez-Pérez, Maria-José; Navarro, Carmen; Barricarte, Aurelio; Zackrisson, Sophia; Almquist, Martin; Hallmans, Goran; Palmqvist, Richard; Tsilidis, Konstantinos K.; Khaw, Kay-Tee; Wareham, Nick; Gallo, Valentina; Jenab, Mazda; Riboli, Elio; Bueno-de-Mesquita, H. Bas

2012-01-01

Existing evidence is inconclusive on whether socioeconomic status (SES) and educational inequalities influence colorectal cancer (CRC) risk, and whether low or high SES/educational level is associated with developing CRC. The aim of our study was to investigate the relationship between educational

Protective effect of fish consumption on colorectal cancer risk. Hospital-based case-control study in Eastern Europe.

Science.gov (United States)

Jedrychowski, Wieslaw; Maugeri, Umberto; Pac, Agnieszka; Sochacka-Tatara, Elzbieta; Galas, Aleksander

2008-01-01

Current epidemiologic studies investigating the effect of fish intake on colorectal cancer (CRC) risk are scarce. Therefore, the aim of this study was to elucidate the relationship between fish consumption and CRC risk. This hospital-based case-control study was performed in 548 CRC patients (Surgery Clinic, University Hospital in Krakow, Poland) between November 2000 and May 2008. Histological findings, information on anatomic location and stage of cancer were available for all the patients enrolled in this study. The control group consisted of 745 patients of the same hospital with no history of cancer admitted for treatment of non-neoplastic conditions. During the 5-year study period, the food frequency questionnaire used focused on the reference period that was defined as 1-5 years prior to CRC diagnosis for the CRC cases and the date of hospital admission for the controls. The crude odds ratio (OR) was inversely related to fish consumption (z for trend in quartiles of intake= -2.31, p=0.021; OR=0.89; 95% confidence interval, CI: 0.81-0.98). The risk of CRC increased with intake of stewed or cooked meat (z for trend in quartiles of intake=2.14; p=0.032; OR=1.11; 95% CI: 1.01-1.23). The adjusted OR showed a significant reduction in CRC already at the moderate fish intake of one or two servings per week (OR=0.70; 95% CI: 0.51-0.94), but it was even lower at higher fish intake (OR=0.56; 95% CI: 0.39-0.86). All multivariate statistical models employed in the analysis considered potential confounders, such as demographic characteristics of subjects, body mass index, smoking status, leisure time physical activity, energy consumption and intake of meat products. The study results indicate that increased fish intake may have a preventive effect on CRC and modulate the effect of meat consumption. To our knowledge, this is the first large epidemiologic study on dietary habits and CRC incidence in Eastern Europe. Copyright 2009 S. Karger AG, Basel.

Performance of continuously reinforced concrete pavements volume 5 : maintenance and repair of CRC pavements.

Science.gov (United States)

1998-10-01

This report is one of a series of reports prepared as part of a recent study sponsored by the Federal Highway Administration (FHWA) aimed at updating the state-of-the-art of the design, construction, maintenance, and rehabiilitation of CRC pavements....

Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different risk profiles may influence clinical management

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Ramsoekh Dewkoemar

2009-12-01

Full Text Available Abstract Background Lynch syndrome (LS is associated with a high risk for colorectal cancer (CRC and extracolonic malignancies, such as endometrial carcinoma (EC. The risk is dependent of the affected mismatch repair gene. The aim of the present study was to calculate the cumulative risk of LS related cancers in proven MLH1, MSH2 and MSH6 mutation carriers. Methods The studypopulation consisted out of 67 proven LS families. Clinical information including mutation status and tumour diagnosis was collected. Cumulative risks were calculated and compared using Kaplan Meier survival analysis. Results MSH6 mutation carriers, both males and females had the lowest risk for developing CRC at age 70 years, 54% and 30% respectively and the age of onset was delayed by 3-5 years in males. With respect to endometrial carcinoma, female MSH6 mutation carriers had the highest risk at age 70 years (61% compared to MLH1 (25% and MSH2 (49%. Also, the age of EC onset was delayed by 5-10 years in comparison with MLH1 and MSH2. Conclusions Although the cumulative lifetime risk of LS related cancer is similar, MLH1, MSH2 and MSH6 mutations seem to cause distinguishable cancer risk profiles. Female MSH6 mutation carriers have a lower CRC risk and a higher risk for developing endometrial carcinoma. As a consequence, surveillance colonoscopy starting at age 30 years instead of 20-25 years is more suitable. Also, prophylactic hysterectomy may be more indicated in female MSH6 mutation carriers compared to MLH1 and MSH2 mutation carriers.

Healthy dietary patterns decrease the risk of colorectal cancer in the Mecca Region, Saudi Arabia: a case-control study.

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Azzeh, Firas S; Alshammari, Eyad M; Alazzeh, Awfa Y; Jazar, Abdelelah S; Dabbour, Ibrahim R; El-Taani, Hani A; Obeidat, Ahmed A; Kattan, Fayrooz A; Tashtoush, Sufyan H

2017-06-29

Colorectal cancer (CRC) is the first most common cancer in males and the third most common cancer in females in Saudi Arabia. Dietary habits are strongly associated with the inhibition or proliferation of malignancy. Therefore, this study is aiming to investigate the risks and protective benefits of dietary factors affecting CRC in the Mecca region of Saudi Arabia. A case-control study was conducted from June 2014 to March 2015. One hundred thirty-seven patients with colon and/or rectal cancer were recruited in the case group, while 164 healthy participants were recruited in the control group. A questionnaire was completed with the help of trained dietitians to study the effects of several dietary patterns on the risk of CRC. Dairy product intake of 1-5 servings/day, legume intake of 3-5 servings/week, leafy vegetables intake of 1-5 servings/week, olive oil intake of 1-5 servings/week, black tea intake of three or more cups/day, and coffee intake of one or more cups/day was found to decrease the risk of CRC in participants. This study highlights the importance of changing dietary habits to decrease CRC incidence in the Mecca region.

Dietary patterns and colorectal cancer risk in a Korean population: A case-control study.

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Park, Yoon; Lee, Jeonghee; Oh, Jae Hwan; Shin, Aesun; Kim, Jeongseon

2016-06-01

Colorectal cancer (CRC) has been recognized as one of the major malignancies in Korea. Analyses of dietary patterns can provide insight into the complex interactions of foods, nutrients, and biologically active components within a diet, which vary among populations. We aimed to investigate the associations between dietary patterns and colorectal cancer risk in Koreans. In a study of 923 cases and 1846 controls, principal component analysis was used to identify dietary patterns based on 33 predefined food groups using a 106-item semiquantitative food frequency questionnaire (SQFFQ). The associations between dietary patterns and CRC risk were assessed using binary and polytomous logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Three dietary patterns (traditional, Westernized, and prudent) were derived. The proportion of total variation explained by 3 patterns was 24.2% for men and 25.3% for women. The traditional and prudent patterns were inversely associated with CRC risk [OR and 95% CI for the highest intake tertile of pattern score vs. the lowest = 0.35 (0.27-0.46) and 0.37 (0.28-0.48), respectively], whereas the Westernized pattern showed a positive association, especially among women [OR = 2.13 (1.35-3.34) for the highest tertile vs. the lowest]. A decrease in CRC risk among those with the highest intake of the prudent pattern was observed in all anatomical subsites in both men [OR = 0.36 (0.19-0.68) for proximal colon; 0.21 (0.12-0.36) for distal colon; 0.28 (0.18-0.44) for rectum] and women [OR = 0.28 (0.11-0.71); 0.27 (0.13-0.54); 0.45 (0.25-0.83)]. Our results indicate that individuals who prefer the Westernized dietary pattern should be made aware of their increased CRC risk. The traditional dietary pattern and the prudent pattern, which are rich in fruits and dairy products, are recommended for the Korean population to prevent CRC.

Incidence and risk of regorafenib-induced hepatotoxicity.

Science.gov (United States)

Zhao, Bin; Zhao, Hong

2017-10-13

Regorafenib, an oral multi-kinase inhibitor, has been approved for the treatments of several malignancies. Unlike traditional cytotoxic chemotherapeutic agents, regorafenib therapy often induces a distinct profile of adverse events (AEs) including hepatotoxicity. Here we conducted an up-to-date meta-analysis to assess the incidence and risk of regorafenib related hepatic toxicities. PubMed and Embase database were reviewed from inception to June 2017 for relevant trials. Eligible studies include subjects with solid tumors treated with 160 mg of regorafenib daily during the first three week of each four-week cycle, and adequate safety data reporting the elevation of aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin. Statistical analyses were conducted to calculate the summary incidence and relative risk (RR). A total of 2,213 subjects from 14 trials were included. The incidences of regorafenib-associated all-grade and high-grade hepatotoxicity were: bilirubin elevation: 23% and 5%; AST elevation: 32% and 6%; ALT elevation: 27% and 5%; ALP elevation: 31% and 2%. Regorafenib-treated subjects had a significant increased risk of all-grade (RR = 3.10; 95% CI, 2.22-4.34) and high-grade (RR = 1.74; 95% CI, 1.09-2.80) bilirubin elevation; all-grade (RR = 1.51; 95% CI, 1.13-2.00) and high-grade (RR = 1.79; 95% CI, 1.00-3.22) AST elevation; all-grade (RR = 1.82; 95% CI, 1.25-2.64) and high-grade (RR = 3.07; 95% CI, 1.30-7.22) ALT elevation; and all-grade (RR = 2.11; 95% CI, 1.01-4.40) ALP elevation. Our results suggest that regorafenib is associated with an increased risk of hepatic toxicities. Hepatotoxicity examination at regular intervals should be advised to clinicians.

A NOVEL APPROACH TO ARRHYTHMIA CLASSIFICATION USING RR INTERVAL AND TEAGER ENERGY

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CHANDRAKAR KAMATH

2012-12-01

Full Text Available It is hypothesized that a key characteristic of electrocardiogram (ECG signal is its nonlinear dynamic behaviour and that the nonlinear component changes more significantly between normal and arrhythmia conditions than the linear component. The usual statistical descriptors used in RR (R to R interval analysis do not capture the nonlinear disposition of RR interval variability. In this paper we explore a novel approach to extract the features from nonlinear component of the RR interval signal using Teager energy operator (TEO. The key feature of Teager energy is that it models the energy of the source that generated the signal rather than the energy of the signal itself. Hence any deviations in regular rhythmic activity of the heart get reflected in the Teager energy function. The classification evaluated on MIT-BIH database, with RR interval and mean of Teager energy computed over RR interval as features, exhibits an average accuracy that exceeds 99.79%.

The coefficient of rolling resistance (CoRR) of some pharmaceutical tablets.

Science.gov (United States)

Ketterhagen, William R; Bharadwaj, Rahul; Hancock, Bruno C

2010-06-15

Experiments have been conducted to measure the coefficient of rolling resistance (CoRR) of some pharmaceutical tablets and several common materials, such as glass beads and steel ball bearings. CoRR values are required as inputs for discrete element method (DEM) models which can be used to model particulate flows and solid dosage form manufacturing processes. Until now there have been no CoRR data reported for pharmaceutical materials, and thus these new data will help to facilitate more accurate modeling of pharmaceutical systems. Copyright 2010 Elsevier B.V. All rights reserved.

Changes in Body Mass Index and Stoma Related Problems in the Elderly

Science.gov (United States)

Skeps, Raymond; McMullen, Carmit K.; Wendel, Christopher S.; Bulkley, Joanna; Grant, Marcia; Mohler, Jane; Hornbrook, Mark C.; Krouse, Robert S.; Herrinton, Lisa J.

2012-01-01

Objectives Weight gain can cause retraction of an intestinal stoma, possibly resulting in difficulty with wafer and pouch fit, daily care challenges, and discomfort. This cross-sectional study examined the association between body mass index (BMI) and ostomy-related problems among long-term (>5 years post-diagnosis) colorectal cancer (CRC) survivors. Materials and Methods CRC survivors from three Kaiser Permanente Regions completed a mailed survey. The response rate for those with an ostomy was 53% (283/529). Questions included stoma-related problems and time to conduct daily ostomy care. Poisson regression evaluated associations between report of problems and change in BMI. Our analysis sample included 235 survivors. Results Sample was 76% ≥65 years of age. Since their surgeries, BMI remained stable in 44% (ST), decreased in 20% (DE), and increased in 35% (IN) of survivors. Compared to ST, male IN (RR 2.15 [1.09–4.25]) and female DE (RR 5.06 [1.26–25.0]) were more likely to spend more than 30 minutes per day on stoma care. IN (vs. ST) were more likely to report interference with clothing (RR 1.51 [1.06–2.17]) and other stoma-related problems (RR 2.32 [1.30–4.14]). Survivors who were obese at time of survey were more likely to report interference with clothing (RR 1.88 [1.38–2.56]) and other stoma-related problems (RR 1.68 [1.07–2.65]). Conclusion A change in BMI is associated with ostomy-related problems among long-term CRC survivors. Equipment and care practices may need to be adapted for changes in abdominal shape. Health care providers should caution that a significant increase or decrease in BMI may cause ostomy-related problems. PMID:24071496

Meta-analysis of the association between COX-2 polymorphisms and risk of colorectal cancer based on case-control studies.

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Qiliu Peng

Full Text Available OBJECTIVE: Cyclooxygenase-2 (COX-2 is an inducible enzyme converting arachidonic acid to prostaglandins and playing important roles in inflammatory diseases as well as tumor development. Previous studies investigating the association between COX-2 polymorphisms and colorectal cancer (CRC risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association. METHODS: All studies published up to October 2013 on the association between COX-2 polymorphisms and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Cochrane library. The association between COX-2 polymorphisms and CRC risk was assessed by odds ratios (ORs together with their 95% confidence intervals (CIs. RESULTS: Ten studies with 6,774 cases and 9,772 controls were included for -1195A>G polymorphism, 13 studies including 6,807 cases and 10,052 controls were available for -765G>C polymorphism, and 8 studies containing 5,121 cases and 7,487 controls were included for 8473T>C polymorphism. With respect to -765G>C polymorphism, we did not find a significant association with CRC risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and cancer location, with a Bonferroni corrected alpha of 0.05/2, statistical significant increased CRC risk was found in the Asian populations (dominant model CC+CG vs. GG: OR = 1.399, 95%CI: 1.113-1.760, P = 0.004 and rectum cancer patients (CC vs. GG: OR = 2.270, 95%CI: 1.295-3.980, P = 0.004; Recessive model CC vs. CG+GG: OR = 2.269, 95%CI: 1.297-3.970, P = 0.004. In subgroup analysis according to source of control, no significant association was detected. With respect to -1195A>G and 8473T>C polymorphisms, no significant association with CRC risk was demonstrated in the overall and subgroup analyses. CONCLUSIONS: The present meta-analysis suggests that the COX-2 -765G>C polymorphism may be a risk factor for

Radiation dose and second cancer risk in patients treated for cancer of the cervix

International Nuclear Information System (INIS)

Boice, J.D. Jr.; Engholm, G.; Kleinerman, R.A.

1988-01-01

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors

Genetic variants and traits related to insulin-like growth factor-I and insulin resistance and their interaction with lifestyles on postmenopausal colorectal cancer risk.

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Su Yon Jung

Full Text Available Genetic variants and traits in metabolic signaling pathways may interact with lifestyle factors such as obesity, physical activity, and exogenous estrogen (E, influencing postmenopausal colorectal cancer (CRC risk, but these interrelated pathways are not fully understood. In this case-cohort study, we examined 33 single-nucleotide polymorphisms (SNPs in genes related to insulin-like growth factor-I (IGF-I/ insulin resistance (IR traits and signaling pathways, using data from 704 postmenopausal women in Women's Health Initiative Observation ancillary studies. Stratifying by the lifestyle modifiers, we assessed the effects of IGF-I/IR traits (fasting total and free IGF-I, IGF binding protein-3, insulin, glucose, and homeostatic model assessment-insulin resistance on CRC risk as a mediator or influencing factor. Six SNPs in the INS, IGF-I, and IGFBP3 genes were associated with CRC risk, and those associations differed between non-obese/active and obese/inactive women and between E nonusers and users. Roughly 30% of the cancer risk due to the SNP was mediated by IGF-I/IR traits. Likewise, carriers of 11 SNPs in the IRS1 and AKT1/2 genes (signaling pathway-related genetic variants had different associations with CRC risk between strata, and the proportion of the SNP-cancer association explained by traits varied from 30% to 50%. Our findings suggest that IGF-I/IR genetic variants interact with obesity, physical activity, and exogenous E, altering postmenopausal CRC risk, through IGF-I/IR traits, but also through different pathways. Unraveling gene-phenotype-lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce CRC risk.

Radial velocities of RR Lyrae stars

International Nuclear Information System (INIS)

Hawley, S.L.; Barnes, T.G. III

1985-01-01

283 spectra of 57 RR Lyrae stars have been obtained using the 2.1-m telescope at McDonald Observatory. Radial velocities were determined using a software cross-correlation technique. New mean radial velocities were determined for 46 of the stars. 11 references

Instrumental variable estimation of the causal effect of plasma 25-hydroxy-vitamin D on colorectal cancer risk: a mendelian randomization analysis.

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Evropi Theodoratou

Full Text Available Vitamin D deficiency has been associated with several common diseases, including cancer and is being investigated as a possible risk factor for these conditions. We reported the striking prevalence of vitamin D deficiency in Scotland. Previous epidemiological studies have reported an association between low dietary vitamin D and colorectal cancer (CRC. Using a case-control study design, we tested the association between plasma 25-hydroxy-vitamin D (25-OHD and CRC (2,001 cases, 2,237 controls. To determine whether plasma 25-OHD levels are causally linked to CRC risk, we applied the control function instrumental variable (IV method of the mendelian randomization (MR approach using four single nucleotide polymorphisms (rs2282679, rs12785878, rs10741657, rs6013897 previously shown to be associated with plasma 25-OHD. Low plasma 25-OHD levels were associated with CRC risk in the crude model (odds ratio (OR: 0.76, 95% Confidence Interval (CI: 0.71, 0.81, p: 1.4×10(-14 and after adjusting for age, sex and other confounding factors. Using an allele score that combined all four SNPs as the IV, the estimated causal effect was OR 1.16 (95% CI 0.60, 2.23, whilst it was 0.94 (95% CI 0.46, 1.91 and 0.93 (0.53, 1.63 when using an upstream (rs12785878, rs10741657 and a downstream allele score (rs2282679, rs6013897, respectively. 25-OHD levels were inversely associated with CRC risk, in agreement with recent meta-analyses. The fact that this finding was not replicated when the MR approach was employed might be due to weak instruments, giving low power to demonstrate an effect (<0.35. The prevalence and degree of vitamin D deficiency amongst individuals living in northerly latitudes is of considerable importance because of its relationship to disease. To elucidate the effect of vitamin D on CRC cancer risk, additional large studies of vitamin D and CRC risk are required and/or the application of alternative methods that are less sensitive to weak instrument

The safety and efficacy of microwave ablation for the treatment of CRC pulmonary metastases.

Science.gov (United States)

Cheng, Gui; Shi, Liangrong; Qiang, Weiguang; Wu, Jun; Ji, Mei; Lu, Qicheng; Li, Xiaodong; Xu, Bin; Jiang, Jingting; Wu, Changping

2017-11-16

Microwave ablation (MWA) is a recently developed thermal ablation technique that has been used for the treatment of different types of tumours. In the present study, we retrospectively evaluated the safety and efficacy of CT-guided percutaneous MWA for the treatment of colorectal cancer (CRC) pulmonary metastases. From June 2010 to June 2015, 48 unresectable lesions in 32 patients with CRC pulmonary metastases were subjected to CT-guided MWA. Imaging follow-up was with contrast-enhanced CT and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Oncologic imaging showed that 42 (87.5%) of the 48 lesions in the 32 patients were completely ablated. Needle track metastatic seeding was not found, and no patient deaths occurred within 30 d after ablation. The mean hospital stay was 3 d (range, 2-7 d). Pneumothorax was the most frequent complication and occurred in 6 (12.5%) of the 48 lesions. The median survival time was 31 months (95% CI: 15.4-46.6). The 1-, 2- and 3-year survival rates were 79.5%, 63.1% and 44.4%, respectively. Univariate Cox regression analysis showed that tumour size, disease-free interval (DFI) and number of tumours were significantly related to the overall survival time (p = .007, p = .022 and p = .030, respectively). Multivariate analysis showed that tumour size was an independent prognostic factor for survival (p = .017). CT-guided percutaneous MWA is a safe and effective minimally invasive method for treating CRC pulmonary metastases.

IRRIGATION PRACTICES IN LONG-TERM SURVIVORS OF COLORECTAL CANCER (CRC) WITH COLOSTOMIES

Science.gov (United States)

Grant, Marcia; McMullen, Carmit K.; Altschuler, Andrea; Hornbrook, Mark C.; Herrinton, Lisa J.; Wendel, Christopher S.; Baldwin, Carol M.; Krouse, Robert S.

2014-01-01

Creation of a colostomy in colorectal (CRC) cancer patients results in a loss of control over bowel evacuation. The only way to re-establish some control is through irrigation, a procedure that involves instilling fluid into the bowel to allow for gas and fecal output. This article reports on irrigation practices of participants in a large, multi-site, multi-investigator study of health-related quality of life (HR-QOL) in long term CRC survivors. Questions about irrigation practices were identified in open-ended questions within a large HR-QOL survey and in focus groups of men and women with high and low HR-QOL. Descriptive data on survivors were combined with content analysis of irrigation knowledge and practices. Patient education and use of irrigation in the United States has decreased over the years, with no clear identification of why this change in practice has occurred. Those respondents who used irrigation had their surgery longer ago, and spent more time in colostomy care than those that did not irrigate. Reasons for the decrease in colostomy irrigation are unreported and present priorities for needed research. PMID:23022935

Contamination of RR Lyrae stars from Binary Evolution Pulsators

Science.gov (United States)

Karczmarek, Paulina; Pietrzyński, Grzegorz; Belczyński, Krzysztof; Stępień, Kazimierz; Wiktorowicz, Grzegorz; Iłkiewicz, Krystian

2016-06-01

Binary Evolution Pulsator (BEP) is an extremely low-mass member of a binary system, which pulsates as a result of a former mass transfer to its companion. BEP mimics RR Lyrae-type pulsations but has different internal structure and evolution history. We present possible evolution channels to produce BEPs, and evaluate the contamination value, i.e. how many objects classified as RR Lyrae stars can be undetected BEPs. In this analysis we use population synthesis code StarTrack.

Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study

DEFF Research Database (Denmark)

Ferrari, P.; McKay, J. D.; Jenab, M.

2012-01-01

BACKGROUND/OBJECTIVES: Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian populati...

Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study

NARCIS (Netherlands)

Moskal, Aurélie; Freisling, Heinz; Byrnes, Graham; Assi, Nada; Fahey, Michael T.; Jenab, Mazda; Ferrari, Pietro; Tjønneland, Anne; Petersen, Kristina EN; Dahm, Christina C.; Hansen, Camilla Plambeck; Affret, Aurélie; Boutron-Ruault, Marie Christine; Cadeau, Claire; Kühn, Tilman; Katzke, Verena; Iqbal, Khalid; Boeing, Heiner; Trichopoulou, Antonia; Bamia, Christina; Naska, Androniki; Masala, Giovanna; de Magistris, Maria Santucci; Sieri, Sabina; Tumino, Rosario; Sacerdote, Carlotta; Peeters, Petra H.; Bueno-de-Mesquita, Bas H.; Engeset, Dagrun; Licaj, Idlir; Skeie, Guri; Ardanaz, Eva; Buckland, Genevieve; Castaño, José M Huerta; Quirós, José R.; Amiano, Pilar; Molina-Portillo, Elena; Winkvist, Anna; Myte, Robin; Ericson, Ulrika; Sonestedt, Emily; Perez-Cornago, Aurora; Wareham, Nick; Khaw, Kay Tee; Huybrechts, Inge; Tsilidis, Konstantinos K.; Ward, Heather; Gunter, Marc J.; Slimani, Nadia

2016-01-01

Background:Much of the current literature on diet–colorectal cancer (CRC) associations focused on studies of single foods/nutrients, whereas less is known about nutrient patterns. We investigated the association between major nutrient patterns and CRC risk in participants of the European Prospective

The Protective Effect of Low-Dose Aspirin against Colorectal Cancer Is Unlikely Explained by Selection Bias: Results from Three Different Study Designs in Clinical Practice.

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Lucía Cea Soriano

Full Text Available We conducted three differently designed nested case-control studies to evaluate whether the protective effect of low-dose aspirin against colorectal cancer (CRC is explained by selection bias.Using a large validated UK primary care database, we followed different cohorts of patients, who varied in their demographic and clinical characteristics, to identify first ever cases of CRC. In Studies 1 and 2, two cohorts were followed, i new users of low-dose aspirin at start of follow-up (N = 170,336 in Study 1, N = 171,527 in Study 2 and either ii non-users of low-dose aspirin (Study 1, N = 170,336 or new users of paracetamol (Study 2, N = 149,597 at start of follow-up. In Study 3 a single cohort of individuals näive to low-dose aspirin at the start of observation was followed. Controls were selected using incidence sampling and logistic regression used to obtain an unbiased estimate of the incidence rate ratio (RR with 95% confidence intervals (CIs. Low-dose aspirin exposure was analyzed 'as-treated' before the index date (CRC date for cases, random date for controls.In the three studies, median (maximum follow-up was 5.1 (12, 5.8 (12 and 7.5 (13 years, respectively. 3033 incident CRC cases were identified in Study 1, 3174 in Study 2, and 12,333 in Study 3. Current use of low-dose aspirin was associated with a significantly reduced risk of 34%, 29% and 31% in the three studies, respectively; corresponding RRs (95% CIs were 0.66 (0.60-0.73, 0.71 (0.63-0.80 and 0.69 (0.64-0.74. In each study, significantly reduced risks of CRC were seen when low-dose aspirin was used for primary or secondary cardiovascular disease prevention, in both sexes, and across all age groups evaluated.Low-dose aspirin is associated with a significantly reduced risk of CRC. The consistency of our findings across different studies makes selection bias an unlikely explanation.

VBLUM photometry of RR Lyrae stars in ω Cen and M4

International Nuclear Information System (INIS)

DeBruijn, J.W.; Lub, J.

1987-01-01

Multicolour VBLUW photometry of RR Lyrae stars in the globular clusters M4 and ω Cen is used to derive information on reddening, blanketing, effective temperatures and gravity of these stars. The methods employed in the literature to determine the reddening of globular clusters from the UBV colours of the RR Lyrae stars are in complete agreement with the results from VBLUW photometry. The most important conclusions of the present work are: the close similarity between the RR Lyrae variables in the field and in globular clusters, and the agreement between the reddenings derived for RR Lyrae in the field and in globular clusters. This means that at least one parameter which normally is taken as a free parameter in studying globular cluster colour magnitude diagrams can be constrained very precisely

CD133 expression is not selective for tumor initiating or radioresistant cell populations in the CRC line HCT-116

International Nuclear Information System (INIS)

Seidel, Claudia; Dietrich, Antje; Wondrak, Marit; Kunz-Schughart, Leoni A.; Grade, Marian; Ried, Thomas

2009-01-01

The hypothesis of certain subpopulations of cancer cells with stem-cell like characteristics that might be responsible for treatment resistance and recurrence of disease is still challenging and under quite controversial discussion. In most studies, surrogate cell surface antigens such as the 92-110 kDa transmembrane glycoprotein CD133 (human Prominin-1) were labeled to isolate particular small cancer cell populations for studying their tumorigenic potential. In colorectal carcinomas (CRC) for example, a small CD133 positive (CD133 + ) cell population has recently been described to be enriched for tumor-initiating/cancer stem cells (TIC/CSC) as compared to the CD133 negative (CD133) population. Furthermore, it was documented that the CD133 + subpopulation could exclusively be maintained in culture as spheres under serum-free conditions. Addition of serum resulted in cell differentiation, growth in 2-D and downregulation of CD133 expression. This would imply that established colorectal cancer (CRC) cell lines that have been grown under adherent, serum-supplemented conditions for years should be devoid of CD133 + cells and TIC/CSC, respectively, which seems contradictory to the finding that many CRC lines produce tumors in nude mice models. In order to gain insight into this paradox, we studied the expression of CD133 in numerous established CRC lines under standard culture conditions and chose one particular cell line based on its expression pattern to study the behavior of CD133 + / CD133 - subpopulations

[Heart rate variability study based on a novel RdR RR Intervals Scatter Plot].

Science.gov (United States)

Lu, Hongwei; Lu, Xiuyun; Wang, Chunfang; Hua, Youyuan; Tian, Jiajia; Liu, Shihai

2014-08-01

On the basis of Poincare scatter plot and first order difference scatter plot, a novel heart rate variability (HRV) analysis method based on scatter plots of RR intervals and first order difference of RR intervals (namely, RdR) was proposed. The abscissa of the RdR scatter plot, the x-axis, is RR intervals and the ordinate, y-axis, is the difference between successive RR intervals. The RdR scatter plot includes the information of RR intervals and the difference between successive RR intervals, which captures more HRV information. By RdR scatter plot analysis of some records of MIT-BIH arrhythmias database, we found that the scatter plot of uncoupled premature ventricular contraction (PVC), coupled ventricular bigeminy and ventricular trigeminy PVC had specific graphic characteristics. The RdR scatter plot method has higher detecting performance than the Poincare scatter plot method, and simpler and more intuitive than the first order difference method.

Healthy dietary patterns decrease the risk of colorectal cancer in the Mecca Region, Saudi Arabia: a case-control study

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Firas S. Azzeh

2017-06-01

Full Text Available Abstract Background Colorectal cancer (CRC is the first most common cancer in males and the third most common cancer in females in Saudi Arabia. Dietary habits are strongly associated with the inhibition or proliferation of malignancy. Therefore, this study is aiming to investigate the risks and protective benefits of dietary factors affecting CRC in the Mecca region of Saudi Arabia. Methods A case-control study was conducted from June 2014 to March 2015. One hundred thirty-seven patients with colon and/or rectal cancer were recruited in the case group, while 164 healthy participants were recruited in the control group. A questionnaire was completed with the help of trained dietitians to study the effects of several dietary patterns on the risk of CRC. Results Dairy product intake of 1–5 servings/day, legume intake of 3–5 servings/week, leafy vegetables intake of 1–5 servings/week, olive oil intake of 1–5 servings/week, black tea intake of three or more cups/day, and coffee intake of one or more cups/day was found to decrease the risk of CRC in participants. Conclusion This study highlights the importance of changing dietary habits to decrease CRC incidence in the Mecca region.

Unmixing the Galactic halo with RR Lyrae tagging

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Belokurov, V.; Deason, A. J.; Koposov, S. E.; Catelan, M.; Erkal, D.; Drake, A. J.; Evans, N. W.

2018-06-01

We show that tagging RR Lyrae stars according to their location in the period-amplitude diagram can be used to shed light on the genesis of the Galactic stellar halo. The mixture of RR Lyrae of ab type, separated into classes along the lines suggested by Oosterhoff, displays a strong and coherent evolution with Galactocentric radius. The change in the RR Lyrae composition appears to coincide with the break in the halo's radial density profile at ˜25 kpc. Using simple models of the stellar halo, we establish that at least three different types of accretion events are necessary to explain the observed RRab behaviour. Given that there exists a correlation between the RRab class fraction and the total stellar content of a dwarf satellite, we hypothesize that the field halo RRab composition is controlled by the mass of the progenitor contributing the bulk of the stellar debris at the given radius. This idea is tested against a suite of cosmological zoom-in simulations of Milky Way-like stellar halo formation. Finally, we study some of the most prominent stellar streams in the Milky Way halo and demonstrate that their RRab class fractions follow the trends established previously.

Gestational age, birth weight, and the risk of hyperkinetic disorder

DEFF Research Database (Denmark)

Linnet, Karen M; Wisborg, Kirsten; Agerbo, Esben

2006-01-01

AIMS: To study the association between gestational age and birth weight and the risk of clinically verified hyperkinetic disorder. METHODS: Nested case-control study of 834 cases and 20 100 controls with incidence density sampling. RESULTS: Compared with children born at term, children born...... with gestational ages of 34-36 completed weeks had a 70% increased risk of hyperkinetic disorder (rate ratio (RR) 1.7, 95% confidence interval (CI) 1.2 to 2.5). Children with gestational ages below 34 completed weeks had an almost threefold increased risk (RR 2.7, 95% CI 1.8 to 4.1). Children born at term...... with birth weights of 1500-2499 g had a 90% increased risk of hyperkinetic disorder (RR 1.9, 95% CI 1.2 to 2.9), and children with birth weights of 2500-2999 g had a 50% increased risk (RR 1.5, 95% CI 1.2 to 1.8) compared with children born at term with birth weights above 2999 g. The results were adjusted...

Polymorphisms in base excision repair genes as colorectal cancer risk factors and modifiers of the effect of diets high in red meat.

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Brevik, Asgeir; Joshi, Amit D; Corral, Román; Onland-Moret, N Charlotte; Siegmund, Kimberly D; Le Marchand, Loïc; Baron, John A; Martinez, Maria Elena; Haile, Robert W; Ahnen, Dennis J; Sandler, Robert S; Lance, Peter; Stern, Mariana C

2010-12-01

A diet high in red meat is an established colorectal cancer (CRC) risk factor. Carcinogens generated during meat cooking have been implicated as causal agents and can induce oxidative DNA damage, which elicits repair by the base excision repair (BER) pathway. Using a family-based study, we investigated the role of polymorphisms in 4 BER genes (APEX1 Gln51His, Asp148Glu; OGG1 Ser236Cys; PARP Val742Ala; and XRCC1 Arg194Trp, Arg280His, Arg399Gln) as potential CRC risk factors and modifiers of the association between diets high in red meat or poultry and CRC risk. We tested for gene-environment interactions using case-only analyses (n = 577) and compared statistically significant results with those obtained using case-unaffected sibling comparisons (n = 307 sibships). Carriers of the APEX1 codon 51 Gln/His genotype had a reduced CRC risk compared with carriers of the Gln/Gln genotype (odds ratio (OR) = 0.15, 95% CI = 0.03-0.69, P = 0.015). The association between higher red meat intake (>3 servings per week) and CRC was modified by the PARP Val762Ala single-nucleotide polymorphisms (SNP; case-only interaction P = 0.026). This SNP also modified the association between higher intake of high-temperature cooked red meat (case-only interaction P = 0.0009). We report evidence that the BER pathway PARP gene modifies the association of diets high in red meat cooked at high temperatures with risk of CRC. Our findings suggest a contribution to colorectal carcinogenesis of free radical damage as one of the possible harmful effects of a diet high in red meat. ©2010 AACR.

Period Changes of 23 Field RR Lyrae Stars

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Soo-Chang Rey

1994-12-01

Full Text Available The secular period behavior of 23 field RR Lyrae stars is studied in order to determine if the observed period changes could be attributed, at least in the mean, to stellar evolution. The sample of stars is subdivided into two Oosterhoff groups based on the metallicity and period-shift. Despite the small sample size, we found a distinct bias toward positive period changes in the group variables. The period changes of the group variables in globular clusters. This provides yet another support for the Lee, Demarque, and Zinn(1990 evolutionary models of RR Lyrae stars and their explanation of the Sandage period-shift effect.

Colorectal cancer risk and nitrate exposure through drinking water and diet.

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Espejo-Herrera, Nadia; Gràcia-Lavedan, Esther; Boldo, Elena; Aragonés, Nuria; Pérez-Gómez, Beatriz; Pollán, Marina; Molina, Antonio J; Fernández, Tania; Martín, Vicente; La Vecchia, Carlo; Bosetti, Cristina; Tavani, Alessandra; Polesel, Jerry; Serraino, Diego; Gómez Acebo, Inés; Altzibar, Jone M; Ardanaz, Eva; Burgui, Rosana; Pisa, Federica; Fernández-Tardón, Guillermo; Tardón, Adonina; Peiró, Rosana; Navarro, Carmen; Castaño-Vinyals, Gemma; Moreno, Victor; Righi, Elena; Aggazzotti, Gabriella; Basagaña, Xavier; Nieuwenhuijsen, Mark; Kogevinas, Manolis; Villanueva, Cristina M

2016-07-15

Ingested nitrate leads to the endogenous synthesis of N-nitroso compounds (NOCs), animal carcinogens with limited human evidence. We aimed to evaluate the risk of colorectal cancer (CRC) associated with nitrate exposure in drinking water and diet. A case-control study in Spain and Italy during 2008-2013 was conducted. Hospital-based incident cases and population-based (Spain) or hospital-based (Italy) controls were interviewed on residential history, water consumption since age 18, and dietary information. Long-term waterborne ingested nitrate was derived from routine monitoring records, linked to subjects' residential histories and water consumption habits. Dietary nitrate intake was estimated from food frequency questionnaires and published food composition databases. Odd ratios (OR) were calculated using mixed models with area as random effect, adjusted for CRC risk factors and other covariables. Generalized additive models (GAMs) were used to analyze exposure-response relationships. Interaction with endogenous nitrosation factors and other covariables was also evaluated. In total 1,869 cases and 3,530 controls were analyzed. Average waterborne ingested nitrate ranged from 3.4 to 19.7 mg/day, among areas. OR (95% CIs) of CRC was 1.49 (1.24, 1.78) for >10 versus ≤5 mg/day, overall. Associations were larger among men versus women, and among subjects with high red meat intake. GAMs showed increasing exposure-response relationship among men. Animal-derived dietary nitrate was associated with rectal, but not with colon cancer risk. In conclusion, a positive association between CRC risk and waterborne ingested nitrate is suggested, mainly among subgroups with other risk factors. Heterogeneous effects of nitrate from different sources (water, animal and vegetables) warrant further research. © 2016 UICC.

Pneumonia risk in asthma patients using inhaled corticosteroids: a quasi-cohort study.

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Qian, Christina J; Coulombe, Janie; Suissa, Samy; Ernst, Pierre

2017-09-01

Studies have linked the use of inhaled corticosteroids (ICSs) to excess pneumonia risk in chronic obstructive pulmonary disease patients. The risk in asthma patients remains unclear. The objective of the present study was to examine the risk of pneumonia with ICSs in asthma patients aged 12-35 years. We formed a cohort of asthma patients treated from 1990 to 2007 using Quebec health insurance databases. Subjects were considered currently exposed if they had had an ICS dispensed within the 60 days prior to their pneumonia index event or matched person-moment. Secondary analyses investigated the risk of pneumonia according to ICS dose and type. Rate ratios (RRs) and rate differences (RDs) were both estimated through a quasi-cohort approach. The cohort included 152 412 subjects, of whom 1928 had a pneumonia event during follow-up. There was an increased risk of pneumonia associated with current use of ICSs [RR 1.83; 95% confidence interval (CI) 1.57, 2.14] or an excess risk of 1.44 cases per 1000 person-years (RD 1.44; 95% CI 1.03, 1.85). There was an excess pneumonia risk with low doses (RR 1.60; 95% CI 1.06, 2.45), moderate doses (RR 1.53; 95% CI 1.12, 2.08) and high doses (RR 1.96; 95% CI 1.64, 2.34) of ICSs, and with budesonide (RR 2.67; 95% CI 2.05, 3.49) and fluticasone (RR 1.93; 95% CI 1.58, 2.36), specifically relative to no use. When accounting for potential protopathic bias, the risk with current use of ICSs was attenuated (RR 1.48; 95% CI 1.22, 1.78). ICS use in asthma patients appears to be associated with an increased risk of pneumonia and is present for both budesonide and fluticasone. © 2017 The British Pharmacological Society.

Association of total energy intake and macronutrient consumption with colorectal cancer risk: results from a large population-based case-control study in Newfoundland and Labrador and Ontario, Canada.

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Sun, Zhuoyu; Liu, Lin; Wang, Peizhong Peter; Roebothan, Barbara; Zhao, Jin; Dicks, Elizabeth; Cotterchio, Michelle; Buehler, Sharon; Campbell, Peter T; McLaughlin, John R; Parfrey, Patrick S

2012-03-26

Diet is regarded as one of the most important environmental factors associated with colorectal cancer (CRC) risk. A recent report comprehensively concluded that total energy intake does not have a simple relationship with CRC risk, and that the data were inconsistent for carbohydrate, cholesterol and protein. The objective of this study was to identify the associations of CRC risk with dietary intakes of total energy, protein, fat, carbohydrate, fiber, and alcohol using data from a large case-control study conducted in Newfoundland and Labrador (NL) and Ontario (ON), Canada. Incident colorectal cancer cases (n = 1760) were identified from population-based cancer registries in the provinces of ON (1997-2000) and NL (1999-2003). Controls (n = 2481) were a random sample of residents in each province, aged 20-74 years. Family history questionnaire (FHQ), personal history questionnaire (PHQ), and food frequency questionnaire (FFQ) were used to collect study data. Logistic regression was used to evaluate the association of intakes of total energy, macronutrients and alcohol with CRC risk. Total energy intake was associated with higher risk of CRC (OR: 1.56; 95% CI: 1.21-2.01, p-trend = 0.02, 5th versus 1st quintile), whereas inverse associations emerged for intakes of protein (OR: 0.85, 95%CI: 0.69-1.00, p-trend = 0.06, 5th versus 1st quintile), carbohydrate (OR: 0.81, 95%CI: 0.63-1.00, p-trend = 0.05, 5th versus 1st quintile) and total dietary fiber (OR: 0.84, 95% CI:0.67-0.99, p-trend = 0.04, 5th versus 1st quintile). Total fat, alcohol, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, and cholesterol were not associated with CRC risk. This study provides further evidence that high energy intake may increase risk of incident CRC, whereas diets high in protein, fiber, and carbohydrate may reduce the risk of the disease.

Association of total energy intake and macronutrient consumption with colorectal cancer risk: results from a large population-based case-control study in Newfoundland and Labrador and Ontario, Canada

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Sun Zhuoyu

2012-03-01

Full Text Available Abstract Background Diet is regarded as one of the most important environmental factors associated with colorectal cancer (CRC risk. A recent report comprehensively concluded that total energy intake does not have a simple relationship with CRC risk, and that the data were inconsistent for carbohydrate, cholesterol and protein. The objective of this study was to identify the associations of CRC risk with dietary intakes of total energy, protein, fat, carbohydrate, fiber, and alcohol using data from a large case-control study conducted in Newfoundland and Labrador (NL and Ontario (ON, Canada. Methods Incident colorectal cancer cases (n = 1760 were identified from population-based cancer registries in the provinces of ON (1997-2000 and NL (1999-2003. Controls (n = 2481 were a random sample of residents in each province, aged 20-74 years. Family history questionnaire (FHQ, personal history questionnaire (PHQ, and food frequency questionnaire (FFQ were used to collect study data. Logistic regression was used to evaluate the association of intakes of total energy, macronutrients and alcohol with CRC risk. Results Total energy intake was associated with higher risk of CRC (OR: 1.56; 95% CI: 1.21-2.01, p-trend = 0.02, 5th versus 1st quintile, whereas inverse associations emerged for intakes of protein (OR: 0.85, 95%CI: 0.69-1.00, p-trend = 0.06, 5th versus 1st quintile, carbohydrate (OR: 0.81, 95%CI: 0.63-1.00, p-trend = 0.05, 5th versus 1st quintile and total dietary fiber (OR: 0.84, 95% CI:0.67-0.99, p-trend = 0.04, 5th versus 1st quintile. Total fat, alcohol, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, and cholesterol were not associated with CRC risk. Conclusion This study provides further evidence that high energy intake may increase risk of incident CRC, whereas diets high in protein, fiber, and carbohydrate may reduce the risk of the disease.

Predictive value of pretreatment lymphocyte count in stage II colorectal cancer and in high-risk patients treated with adjuvant chemotherapy.

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Liang, Lei; Zhu, Ji; Jia, Huixun; Huang, Liyong; Li, Dawei; Li, Qingguo; Li, Xinxiang

2016-01-05

Pretreatment lymphocyte count (LC) has been associated with prognosis and chemotherapy response in several cancers. The predictive value of LC for stage II colorectal cancer (CRC) and for high-risk patients treated with adjuvant chemotherapy (AC) has not been determined. A retrospective review of prospectively collected data from 1332 consecutive stage II CRC patients who underwent curative tumor resection was conducted. A pretreatment LC value risk, 459 (62.2%) of whom received AC. Patients with low LCs had significantly worse 5-year OS (74.6% vs. 90.2%, p risk patients with low LCs had the poorest DFS (p value or combined with high-risk status were both independent prognostic factors(p risk, AC-treated patients with high LCs had significantly longer DFS than untreated patients (HR, 0.594; 95% CI, 0.364-0.970; p = 0.035). There was no difference or trend for DFS or OS in patients with low LCs, regardless of the use of AC (DFS, p = 0.692; OS, p = 0.522). Low LC was also independently associated with poorer DFS in high-risk, AC-treated patients (HR, 1.885; 95% CI, 1.112-3.196; p = 0.019). Pretreatment LC is an independent prognostic factor for survival in stage II CRC. Furthermore, pretreatment LC reliably predicts chemotherapeutic efficacy in high-risk patients with stage II CRC.

QT/RR Coupling and Gender Differences

Czech Academy of Sciences Publication Activity Database

Halámek, Josef; Jurák, Pavel; Lipoldová, J.; Leinveber, Pavel

2010-01-01

Roč. 37, - (2010), s. 365-368 ISSN 0276-6574 R&D Projects: GA ČR GA102/08/1129 Institutional research plan: CEZ:AV0Z20650511 Keywords : THEW * QT/RR model * EXPDC Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering http://cinc.mit.edu/archives/2010/pdf/0365.pdf

Risk of Stroke in Migraineurs Using Triptans. Associations with Age, Sex, Stroke Severity and Subtype

DEFF Research Database (Denmark)

Albieri, Vanna; Olsen, Tom Skyhøj; Andersen, Klaus Kaae

2016-01-01

for a first stroke were identified in the Danish Registries. Information on stroke severity/subtype and cardiovascular risk factors was available for stroke patients. FINDINGS: Of the 49,711 patients hospitalized for a first stroke, 1084 were migraineurs using triptans. Adjusting for age, sex, income......, and educational level, risk for stroke was higher among migraineurs in respect to all strokes (RR 1.07; CI 1.01-1.14) and ischemic strokes (RR 1.07; CI 1.00-1.14). Risk for hemorrhagic stroke was increased but only in women (RR 1.41; CI 1.11-1.79). Risk was for mild strokes (RR 1.31; CI 1.16-1.48) while risk...

Lycopene and risk of cardiovascular diseases: A meta-analysis of observational studies.

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Song, Bo; Liu, Kai; Gao, Yuan; Zhao, Lu; Fang, Hui; Li, Yusheng; Pei, Lulu; Xu, Yuming

2017-09-01

The aim of current meta-analysis was to investigate the relation between lycopene and risk of cardiovascular diseases (CVD). Studies concerning about the association between lycopene and risk of CVD were searched on Pubmed, Embase, and Web of Science from inception to October 2016. A total of 14 eligible studies were identified. A significantly inverse association with a pooled risk ratio (RR) of 0.83 (95% CI: 0.76-0.90) was shown between lycopene exposure and risk of CVD. Findings were similar restricting to dietary studies (RR = 0.87, 95% CI = 0.79-0.96) and biomarker studies (RR = 0.74, 95% CI = 0. 62-0.87).Dietary lycopene intake was statistically significant for coronary heart disease (CHD) (RR: 0.87; 95% CI: 0.76-0.98) and stroke (RR: 0.83; 95% CI: 0.69-0.96).The pooled risk estimate was generally similar for lycopene biomarker concentrations, but the association was only statistically significant for stroke (RR: 0.65; 95% CI: 0.42-0.87). Subgroup analyses showed that retrospective and low quality studies were statistically significant sources of heterogeneity. Higher lycopene exposure is inversely associated with a lower risk of CVD. Further well-designed randomized clinical trials are required to assess the role of lycopene on CVD. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recurrence of Subdural Haematoma in a Population-Based Cohort - Risks and Predictive Factors.

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Linnea Schmidt

Full Text Available To estimate the risks of and identify predictors for recurrent subdural haematoma in surgically and conservatively treated patients.The cohort comprised all individuals diagnosed with a first-time subdural hematoma in Denmark 1996-2011. Information on potential predictors was retrieved from the Danish health registers. Cumulative recurrence risks were estimated using the Aalen-Johansen estimator. Rate ratios (RR were estimated using Poisson regression.Among 10,158 individuals with a subdural hematoma, 1,555 had a recurrent event. The cumulative risk of recurrent subdural hematoma was 9% at 4 weeks after the primary bleeding, increasing to and stabilising at 14% after one year. Predictors associated with recurrence were: Male sex (RR 1.60, 95% CI:1.43-1.80, older age (>70 years compared to 20-49 years; RR 1.41, 95% CI: 1.21-1.65, alcohol addiction (RR 1.20, 95% CI:1.04-1.37, surgical treatment (RR 1.76, 95% CI:1.58-1.96, trauma diagnoses (RR 1.14, 95% CI:1.03-1.27, and diabetes mellitus (RR 1.40, 95% CI:1.11-1.74. Out of a selected combination of risk factors, the highest cumulative 1-year recurrence risks for subdural hematoma of 25% (compared to 14% for all patients was found in surgically treated males with diabetes mellitus.The recurrence risk of subdural hematoma is largely limited to the first year. Patient characteristics including co-morbidities greatly influence the recurrence risk of SDH, suggesting that individualized prognostic guidance and follow-up is needed.

New trend in colorectal cancer in Germany: are young patients at increased risk for advanced colorectal cancer?

Science.gov (United States)

Ambe, Peter C; Jansen, Stefan; Zirngibl, Hubert

2017-08-23

The role of colonoscopy in the screening of colorectal cancer (CRC) has been unequivocally established. In Germany, screening colonoscopy with full insurance reimbursement is available for individuals aged 55 and above, and/or for persons with well-known risk factors for CRC. However, advanced CRC is not uncommon in individuals below 55 years. This study was designed to investigate the incidence of advanced CRC in patients < 55 years. A retrospective analysis of data from a prospectively maintained CRC database of a university hospital in Germany was performed. Using the recommended age for screening colonoscopy as cutoff, the study population was divided into two groups: < 55 years (study group) and ≥ 55 years (control group). Both groups were compared with regard to the extent of CRC using the UICC stages. Only surgically managed patients were included for analysis. Advanced CRC was defined as UICC stage III or IV. Complete follow-up data was available for 609 patients treated between 2009 and 2013. The study group included 83 patients, 42 females and 41 males with a median age of 48.0 ± 10 years, while the control group was made up of 526 patients, 230 females and 296 males with a median age of 75.5 ± 8.3 years. Both groups were comparable with regard to gender distribution, p = 0.24. Significantly more patients from the study group were diagnosed with advanced CRC in comparison to the control group, 56.6 vs. 43.9%, p = 0.03. There was no statistically significant difference amongst both groups with respect to cancer-related mortality, 10.8 vs. 12.5%, p = 0.66. Patients below the recommended age for screening colonoscopy might be at increased risk for advanced CRC. There is need to decrease the recommended age for screening colonoscopy to prevent CRC or enable an early diagnosis in patients below 55 years.

Frequent Use of Antibiotics Is Associated with Colorectal Cancer Risk: Results of a Nested Case-Control Study

NARCIS (Netherlands)

Dik, V.K.; Oijen, M.G. van; Smeets, H.M.; Siersema, P.D.

2016-01-01

BACKGROUND: Microbiotical dysbiosis induced by a Western diet seems to be associated with an increased risk of developing colorectal cancer (CRC). Few other factors with an effect on the colonic microbiota and their association with CRC have been evaluated. AIM: We investigated whether the use of

Frequent Use of Antibiotics Is Associated with Colorectal Cancer Risk : Results of a Nested Case-Control Study

NARCIS (Netherlands)

Dik, Vincent K; van Oijen, Martijn G H; Smeets, Hugo M.; Siersema, Peter D

2016-01-01

BACKGROUND: Microbiotical dysbiosis induced by a Western diet seems to be associated with an increased risk of developing colorectal cancer (CRC). Few other factors with an effect on the colonic microbiota and their association with CRC have been evaluated. AIM: We investigated whether the use of

A Polymorphic Enhancer near GREM1 Influences Bowel Cancer Risk through Differential CDX2 and TCF7L2 Binding

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Annabelle Lewis

2014-08-01

Full Text Available A rare germline duplication upstream of the bone morphogenetic protein antagonist GREM1 causes a Mendelian-dominant predisposition to colorectal cancer (CRC. The underlying disease mechanism is strong, ectopic GREM1 overexpression in the intestinal epithelium. Here, we confirm that a common GREM1 polymorphism, rs16969681, is also associated with CRC susceptibility, conferring ∼20% differential risk in the general population. We hypothesized the underlying cause to be moderate differences in GREM1 expression. We showed that rs16969681 lies in a region of active chromatin with allele- and tissue-specific enhancer activity. The CRC high-risk allele was associated with stronger gene expression, and higher Grem1 mRNA levels increased the intestinal tumor burden in ApcMin mice. The intestine-specific transcription factor CDX2 and Wnt effector TCF7L2 bound near rs16969681, with significantly higher affinity for the risk allele, and CDX2 overexpression in CDX2/GREM1-negative cells caused re-expression of GREM1. rs16969681 influences CRC risk through effects on Wnt-driven GREM1 expression in colorectal tumors.

Polymorphisms in the xenobiotic transporter Multidrug Resistance 1 (MDR1 and interaction with meat intake in relation to risk of colorectal cancer in a Danish prospective case-cohort study

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Overvad Kim

2009-11-01

Full Text Available Abstract Background The xenobiotic transporters, Multidrug Resistance 1 (MDR1/ABCB1 and Breast Cancer Resistance Protein (BCRP/ABCG2 may restrict intestinal absorption of various carcinogens, including heterocyclic amines (HCA and polycyclic aromatic hydrocarbons (PAH. Cyclooxygenase-2 (COX-2 derived prostaglandins promote gastrointestinal carcinogenesis, affecting angiogenesis, apoptosis, and invasiveness. The aim of this study was to investigate if polymorphisms in these genes were associated with risk of colorectal cancer (CRC, and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. Methods The following polymorphisms were analyzed; a synonymous MDR1 C3435T (rs1045642 in exon26, G-rs3789243-A in intron3, the functional BCRP C421A (rs2231142, the two COX-2 A-1195G (rs689466 and G-765C (rs20417 in the promoter region, and the COX-2 T8473C (rs5275 polymorphisms in the 3'-untranslated region. The polymorphisms were assessed together with lifestyle factors in a nested case-cohort study of 359 cases and a random cohort sample of 765 participants from the Danish prospective Diet, Cancer and Health study. Results Carriers of the variant allele of MDR1 intron 3 polymorphism were at 1.52-fold higher risk of CRC than homozygous wild type allele carriers (Incidence rate ratio (IRR = 1.52, 95% Confidence Interval (CI: 1.12-2.06. Carriers of the variant allele of MDR1 C3435T exon 26 had a lower risk of CRC than homozygous C-allele carriers (IRR = 0.71 (CI:0.50-1.00. There was interaction between these MDR1 polymorphisms and intake of red and processed meat in relation to CRC risk. Homozygous MDR1 C3435T C-allele carriers were at 8% increased risk pr 25 gram meat per day (CI: 1.00-1.16 whereas variant allele carriers were not at increased risk (p for interaction = 0.02. COX-2 and BCRP polymorphisms were not associated with CRC risk. There was interaction between NSAID use and MDR1 C3435T and COX-2 T

Polymorphisms in the xenobiotic transporter Multidrug Resistance 1 (MDR1) and interaction with meat intake in relation to risk of colorectal cancer in a Danish prospective case-cohort study

International Nuclear Information System (INIS)

Andersen, Vibeke; Østergaard, Mette; Christensen, Jane; Overvad, Kim; Tjønneland, Anne; Vogel, Ulla

2009-01-01

The xenobiotic transporters, Multidrug Resistance 1 (MDR1/ABCB1) and Breast Cancer Resistance Protein (BCRP/ABCG2) may restrict intestinal absorption of various carcinogens, including heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH). Cyclooxygenase-2 (COX-2) derived prostaglandins promote gastrointestinal carcinogenesis, affecting angiogenesis, apoptosis, and invasiveness. The aim of this study was to investigate if polymorphisms in these genes were associated with risk of colorectal cancer (CRC), and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. The following polymorphisms were analyzed; a synonymous MDR1 C3435T (rs1045642) in exon26, G-rs3789243-A in intron3, the functional BCRP C421A (rs2231142), the two COX-2 A-1195G (rs689466) and G-765C (rs20417) in the promoter region, and the COX-2 T8473C (rs5275) polymorphisms in the 3'-untranslated region. The polymorphisms were assessed together with lifestyle factors in a nested case-cohort study of 359 cases and a random cohort sample of 765 participants from the Danish prospective Diet, Cancer and Health study. Carriers of the variant allele of MDR1 intron 3 polymorphism were at 1.52-fold higher risk of CRC than homozygous wild type allele carriers (Incidence rate ratio (IRR) = 1.52, 95% Confidence Interval (CI): 1.12-2.06). Carriers of the variant allele of MDR1 C3435T exon 26 had a lower risk of CRC than homozygous C-allele carriers (IRR = 0.71 (CI:0.50-1.00)). There was interaction between these MDR1 polymorphisms and intake of red and processed meat in relation to CRC risk. Homozygous MDR1 C3435T C-allele carriers were at 8% increased risk pr 25 gram meat per day (CI: 1.00-1.16) whereas variant allele carriers were not at increased risk (p for interaction = 0.02). COX-2 and BCRP polymorphisms were not associated with CRC risk. There was interaction between NSAID use and MDR1 C3435T and COX-2 T8473C (p-values for interaction 0

Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations.

Science.gov (United States)

Sheth, Harsh; Northwood, Emma; Ulrich, Cornelia M; Scherer, Dominique; Elliott, Faye; Barrett, Jennifer H; Forman, David; Wolf, C Roland; Smith, Gillian; Jackson, Michael S; Santibanez-Koref, Mauro; Haile, Robert; Casey, Graham; Jenkins, Mark; Win, Aung Ko; Hopper, John L; Marchand, Loic Le; Lindor, Noralane M; Thibodeau, Stephen N; Potter, John D; Burn, John; Bishop, D Timothy

2018-01-01

Regular aspirin use is associated with reduced risk of colorectal cancer (CRC). Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs). We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs) and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All Paspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively); stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68-0.86; rs1105879 OR = 0.77 95% CI = 0.69-0.86) compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively), with the direction of association similar to that observed for CRC. Additionally, they showed interaction between any non-steroidal anti-inflammatory drugs (including aspirin) use and CRC risk (Pinteraction = 0.01 for both). All gene x environment (GxE) interactions however were not significant after multiple test correction. Candidate gene investigation indicated no evidence of GxE interaction between genetic variants in genes involved in aspirin pathways, regular aspirin use and colorectal cancer

Interaction between interleukin-10 (IL-10 polymorphisms and dietary fibre in relation to risk of colorectal cancer in a Danish case-cohort study

Directory of Open Access Journals (Sweden)

Andersen Vibeke

2012-05-01

Full Text Available Abstract Background More than 50% of the colorectal cancer (CRC etiology has been attributed to diet. Established or suspected dietary factors modifying risk of CRC are red meat, cereals, fish, and fibre. Diet and lifestyle may be linked to cancer through inflammation. Interleukin-10 (IL-10 is an anti-inflammatory cytokine. We wanted to test if dietary factors and IL10 polymorphisms interact in relation to colorectal carcinogenesis. Methods The functional IL10 polymorphism C-592A (rs1800872 and the marker rs3024505 were assessed in relation to diet and lifestyle in a nested case-cohort study of 378 CRC cases and 775 randomly selected participants from a prospective study of 57,053 persons. Genotyping data on the IL10 polymorphism C-592A, smoking and non-steroidal anti-inflammatory drugs (NSAID was retrieved from Vogel et al. (Mutat Res, 2007; 624:88. Incidence rate ratios (IRR and 95% Confidence Interval (95% CI were calculated. Results No associations were found between the IL10 rs3024505 polymorphism and risk of CRC. There was interaction between rs3024505 and dietary fibre (P-value for interaction = 0.01. IL10 rs3024505 homozygous wildtype carriers were at 27% reduced risk of CRC per 10 g fibre per day (95% CI: 0.60-0.88 whereas variant carriers had no risk reduction by fibre intake. Also, interaction between IL10 C-592A and intake of fibre was found (P-value for interaction = 0.02. Among those eating IL10 polymorphisms and dietary meat, cereal, or fish intake, or between IL10 rs3024505 and smoking or NSAID use were found. Conclusions In this northern Caucasian cohort we found interaction between IL10 and dietary fibre in CRC carcinogenesis. High intake of fibre seems to protect against CRC among individuals with IL10 related genetic susceptibility to CRC. This finding should be evaluated in other prospective and population-based cohorts with different ethnic groups.

Firearm Violence Among High-Risk Emergency Department Youth After an Assault Injury

Science.gov (United States)

Walton, Maureen A.; Roehler, Douglas R.; Goldstick, Jason; Zimmerman, Marc A.; Blow, Frederic C.; Cunningham, Rebecca M.

2015-01-01

BACKGROUND: The risk for firearm violence among high-risk youth after treatment for an assault is unknown. METHODS: In this 2-year prospective cohort study, data were analyzed from a consecutive sample of 14- to 24-year-olds with drug use in the past 6 months seeking assault-injury care (AIG) at an urban level 1 emergency department (ED) compared with a proportionally sampled comparison group (CG) of drug-using nonassaulted youth. Validated measures were administered at baseline and follow-up (6, 12, 18, 24 months). RESULTS: A total of 349 AIG and 250 CG youth were followed for 24 months. During the follow-up period, 59% of the AIG reported firearm violence, a 40% higher risk than was observed among the CG (59.0% vs. 42.5%; relative risk [RR] = 1.39). Among those reporting firearm violence, 31.7% reported aggression, and 96.4% reported victimization, including 19 firearm injuries requiring medical care and 2 homicides. The majority with firearm violence (63.5%) reported at least 1 event within the first 6 months. Poisson regression identified baseline predictors of firearm violence, including male gender (RR = 1.51), African American race (RR = 1.26), assault-injury (RR = 1.35), firearm possession (RR = 1.23), attitudes favoring retaliation (RR = 1.03), posttraumatic stress disorder (RR = 1.39), and a drug use disorder (RR = 1.22). CONCLUSIONS: High-risk youth presenting to urban EDs for assault have elevated rates of subsequent firearm violence. Interventions at an index visit addressing substance use, mental health needs, retaliatory attitudes, and firearm possession may help decrease firearm violence among urban youth. PMID:25847808

Identification of atrial fibrillation using electrocardiographic RR-interval difference

Science.gov (United States)

Eliana, M.; Nuryani, N.

2017-11-01

Automated detection of atrial fibrillation (AF) is an interesting topic. It is an account of very dangerous, not only as a trigger of embolic stroke, but it’s also related to some else chronical disease. In this study, we analyse the presence of AF by determining irregularities of RR-interval. We utilize the interval comparison to measure the degree of irregularities of RR-interval in a defined segment. The series of RR-interval is segmented with the length of 10 of them. In this study, we use interval comparison for the method. We were comparing all of the intervals there each other. Then we put the threshold to define the low difference and high difference (δ). A segment is defined as AF or Normal Sinus by the number of high δ, so we put the tolerance (β) of high δ there. We have used this method to test the 23 patients data from MIT-BIH. Using the approach and the clinical data we find accuracy, sensitivity, and specificity of 84.98%, 91.99%, and 77.85% respectively.

CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 8 AND 9 CRYSTAL RIVER UNIT 3

International Nuclear Information System (INIS)

Wilson, Michael L.

2001-01-01

The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 8 and 9 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies

Genetic polymorphisms of superoxide dismutase-1 A251G and catalase C-262T with the risk of colorectal cancer.

Science.gov (United States)

Jamhiri, Iman; Saadat, Iraj; Omidvari, Shahpour

2017-06-01

Oxidative stress is significant in numerous types of disease including cancer. To protect cells and organs against reactive oxygen species (ROS), the body has evolved an antioxidant protection system that involved in the detoxification of ROS. Single nucleotide polymorphisms (SNP) of anti-oxidative enzymes may dramatically change the activity of the encoded proteins; therefore, certain alleles can be established as risk factors for some kind of multi-factorial diseases including cancer. In present study we investigate the possible association between polymorphisms of superoxide dismutase 1 ( SOD1 , OMIM: 147450) and catalase ( CAT , OMIM: 115500) genes and the risk of colorectal cancer (CRC). The study included 204 colorectal cancer patients and 239 healthy control group matched for gender and age. Genotyping of SOD1 A251G and CAT C-262T were done by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. There was no significant association between CAT C-262T polymorphism and susceptibility to CRC (P>0.05). The carries of the G allele of SOD1 significantly showed higher prevalence in CRC patients compared with the control group (OR=1.84, 95% CI=1.13-2.98, P=0.013). We assessed the effect of combination of genotypes of the study polymorphisms on the risk of CRC. We found that the combination of AG+GG ( SOD1 ) and CC ( CAT ) increases the risk of developing CRC (OR=2.38, 95% CI=1.25-4.52, P=0.008).

Food groups and nutrient intake and risk of colorectal cancer: a hospital-based case-control study in Spain.

Science.gov (United States)

Banqué, Marta; Raidó, Blanca; Masuet, Cristina; Ramon, Josep M

2012-04-01

Although evidence supports that colorectal cancer (CRC) has an environmental etiology, the potential influence of diet appears to be one of the most important components. We studied the relation between food groups and nutrient intake and the risk of CRC. A hospital-based case-control study was conducted in Spain between 2007 and 2009. The authors matched 245 patients with incident histologically confirmed CRC by age, gender, and date of admission with 490 controls. Information about nutrient intake was gathered by using a semiquantitative frequency food questionnaire. Univariate analysis was done with individual food items. Odds ratios (ORs) for consecutive tertiles of nutrient intake were computed after allowance for sociodemographic variables and consumption of food groups. Vitamin B6 (OR: 0.26), vitamin D (OR: 0.45), vitamin E (OR: 0.42), polyunsaturated fatty acids (OR: 0.57), and fiber (OR: 0.40) were inversely associated with CRC, whereas carbohydrates (OR: 1.82) were significantly associated with CRC risk for the upper tertile. In multivariate analysis adjusting for major covariables (energy, age, and gender), vitamin D (OR:0.45), vitamin E (OR:0.36), and fiber (OR:0.46) remained associated with CRC. Data suggest that the etiology of colorectal cancer is not due to lifestyle and dietary patterns being important the effect of single nutrients.

77 FR 27085 - R.R. Donnelley, Inc., Bloomsburg, PA; Notice of Negative Determination on Reconsideration

Science.gov (United States)

2012-05-08

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-80,485] R.R. Donnelley, Inc... workers of R.R. Donnelley, Inc., Bloomsburg, Pennsylvania (subject firm). The Department's Notice of... eligibility to apply for worker adjustment assistance for workers and former workers of R.R. Donnelley, Inc...

Finite element analysis and experimental verification of Polymer reinforced CRC improved for close-in detonation

DEFF Research Database (Denmark)

Riisgaard, Benjamin; Georgakis, Christos; Stang, Henrik

2007-01-01

Compact Reinforced Composite, CRC, is a high-strength cement-based composite that holds an enormous flexural and energy-absorbing capacity due to the close-spaced high strength steel reinforcement and a high-strength cement-based fiber DSP matrix. The material has been used in various constructions...

Prospective evaluation of trans-fatty acid intake and colorectal cancer risk in the Iowa Women’s Health Study

OpenAIRE

Limburg, Paul J.; Liu-Mares, Wen; Vierkant, Robert A.; Wang, Alice H.; Harnack, Lisa; Flood, Andrew P.; Sellers, Thomas A.; Cerhan, James R.

2008-01-01

Concerns regarding the safety of dietary trans-fatty acids (tFAs) have generated recent public interest, scientific discussion and legislative action. Although most widely recognized as a risk factor for cardiovascular disease, associations between tFA intake and incident cancer have also been proposed. With respect to colorectal cancer (CRC), existing observational data remain limited and inconclusive. Therefore, we conducted a prospective evaluation of tFA intake and CRC risk, overall and b...

HLA-G 3'UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment.

Science.gov (United States)

Garziera, Marica; Bidoli, Ettore; Cecchin, Erika; Mini, Enrico; Nobili, Stefania; Lonardi, Sara; Buonadonna, Angela; Errante, Domenico; Pella, Nicoletta; D'Andrea, Mario; De Marchi, Francesco; De Paoli, Antonino; Zanusso, Chiara; De Mattia, Elena; Tassi, Renato; Toffoli, Giuseppe

2015-01-01

An important hallmark of CRC is the evasion of immune surveillance. HLA-G is a negative regulator of host's immune response. Overexpression of HLA-G protein in primary tumour CRC tissues has already been associated to worse prognosis; however a definition of the role of immunogenetic host background is still lacking. Germline polymorphisms in the 3'UTR region of HLA-G influence the magnitude of the protein by modulating HLA-G mRNA stability. Soluble HLA-G has been associated to 3'UTR +2960 Ins/Ins and +3035 C/T (lower levels) and +3187 G/G (high levels) genotypes. HLA-G 3'UTR SNPs have never been explored in CRC outcome. The purpose of this study was to investigate if common HLA-G 3'UTR polymorphisms have an impact on DFS and OS of 253 stage II-III CRC patients, after primary surgery and ADJ-CT based on FL. The 3'UTR was sequenced and SNPs were analyzed for their association with survival by Kaplan-Meier and multivariate Cox models; results underwent internal validation using a resampling method (bootstrap analysis). In a multivariate analysis, we estimated an association with improved DFS in Ins allele (Ins/Del +Ins/Ins) carriers (HR 0.60, 95% CI 0.38-0.93, P = 0.023) and in patients with +3035 C/T genotype (HR 0.51, 95% CI 0.26-0.99, P = 0.045). The +3187 G/G mutated carriers (G/G vs A/A+A/G) were associated to a worst prognosis in both DFS (HR 2.46, 95% CI 1.19-5.05, P = 0.015) and OS (HR 2.71, 95% CI 1.16-6.63, P = 0.022). Our study shows a prognostic and independent role of 3 HLA-G 3'UTR SNPs, +2960 14-bp INDEL, +3035 C>T, and +3187 A>G.

A shift from distal to proximal neoplasia in the colon: a decade of polyps and CRC in Italy

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Panzone Sergio

2010-11-01

Full Text Available Abstract Background In the last years a trend towards proximalization of colorectal carcinomas (CRC has been reported. This study aims to evaluate the distribution of CRC and adenomatous polyps (ADP to establish the presence of proximalization and to assess the potential predictors. Methods We retrieved histology reports of colonic specimens excised during colonoscopy, considering the exams performed between 1997 and 2006 at Cuneo Hospital, Italy. We compared the proportion of proximal lesions in the period 1997-2001 and in the period 2002-2006. Results Neoplastic lesions were detected in 3087 people. Proximal CRC moved from 25.9% (1997-2001 to 30.0% (2002-2006. Adjusting for sex and age, the difference was not significant (OR 1.23; 95% CI: 0,95-1,58. The proximal ADP proportion increased from 19.2% (1997-2001 to 26.0% (2002-2006 (OR: 1.43; 95% CI: 1.17-1.89. The corresponding figures for advanced proximal ADP were 6.6% and 9.5% (OR: 1.48; 95% CI: 1.02-2.17. Adjusting for gender, age, diagnostic period, symptoms and number of polyps the prevalence of proximal advanced ADP was increased among people ≥ 70 years compared to those aged 55-69 years (OR 1.49; 95% CI: 1.032.16. The main predictor of proximal advanced neoplasia was the number of polyps detected per exam (> 1 polyp versus 1 polyp: considering all ADP: OR 2.16; 95% CI: 1.59-2.93; considering advanced ADP OR 1.63; 95% CI: 1.08-2.46. Adjusting for these factors, the difference between the two periods was no longer significant. Conclusions CRC do not proximalize while a trend towards a proximal shift in adenomas was observed among people ≥ 70 years.

Consumption of Whole-Grain Bread and Risk of Colorectal Cancer among Norwegian Women (the NOWAC Study)

OpenAIRE

Bakken, Toril; Braaten, Tonje; Olsen, Anja; Kyrø, Cecilie; Lund, Eiliv; Skeie, Guri

2016-01-01

Published version. Source at http://doi.org/10.3390/nu8010040. License CC BY 4.0. There is evidence that consumption of foods containing dietary fiber decreases the risk of colorectal cancer (CRC). Whole grains contain dietary fiber, as well as a range of micronutrients and bioactive compounds, but the association between the consumption of whole grains and the risk of CRC remains less studied. The aim of the present study was to investigate the association between whole-grain bread con...

The Int7G24A variant of transforming growth factor-beta receptor type I is a risk factor for colorectal cancer in the male Spanish population: a case-control study

International Nuclear Information System (INIS)

Castillejo, Adela; Guillén-Ponce, Carmen; Carrato, Alfredo; Soto, José-Luís; Mata-Balaguer, Trinidad; Guarinos, Carla; Castillejo, María-Isabel; Martínez-Cantó, Ana; Barberá, Víctor-Manuel; Montenegro, Paola; Ochoa, Enrique; Lázaro, Rafael

2009-01-01

The Int7G24A variant of transforming growth factor-beta receptor type I (TGFBR1) has been shown to increase the risk for kidney, ovarian, bladder, lung and breast cancers. Its role in colorectal cancer (CRC) has not been established. The aims of this study were to assess the association of TGFBR1*Int7G24A variant with CRC occurrence, patient age, gender, tumour location and stage. We performed a case-control study with 504 cases of sporadic CRC; and 504 non-cancerous age, gender and ethnically matched controls. Genotyping analysis was performed using allelic discrimination assay by real time PCR. The Int7G24A variant was associated with increased CRC incidence in an additive model of inheritance (P for trend = 0.005). No significant differences were found between Int7G24A genotypes and tumour location or stage. Interestingly, the association of the Int7G24A variant with CRC risk was significant in men (odds ratio 4.10 with 95% confidence intervals 1.41-11.85 for homozygous individuals; P for trend = 0.00023), but not in women. We also observed an increase in susceptibility to CRC for individuals aged less than 70 years. Our data suggest that the Int7G24A variant represents a risk factor for CRC in the male Spanish population

Identification of patients at risk for colorectal cancer in primary care: an explorative study with routine healthcare data

NARCIS (Netherlands)

Koning, N.R; Moons, L.N.G; Büchner, F.L.; Helsper, C.W.; ten Teije, A.C.M.; Numans, M.E.

2015-01-01

Background Early diagnosis of colorectal cancer (CRC) is likely to reduce burden of disease and improve treatment success. Estimation of the individual patient risk for CRC diagnostic determinants in a primary care setting has not been very successful as yet. The aim of our study is to improve

Maternal Obesity: Risks for Developmental Delays in Early Childhood.

Science.gov (United States)

Duffany, Kathleen O'Connor; McVeigh, Katharine H; Kershaw, Trace S; Lipkind, Heather S; Ickovics, Jeannette R

2016-02-01

To assess the risk for neurodevelopmental delays for children of mothers who were obese (≥200 pounds) prior to pregnancy, and to characterize delays associated with maternal obesity among children referred to and found eligible to receive Early Intervention Program services. We conducted a retrospective cohort study (N = 541,816) using a population-based New York City data warehouse with linked birth and Early Intervention data. Risks for children suspected of a delay and 'significantly delayed', with two moderate or one severe delay, were calculated. Among the group of children eligible by delay for Early Intervention, analyses assessed risk for being identified with a moderate-to-severe delay across each of five functional domains as well as risks for multiple delays. Children of mothers who were obese were more likely to be suspected of a delay (adjusted RR 1.19 [CI 1.15-1.22]) and borderline association for 'significantly delayed' (adjusted RR 1.01 [CI 1.00-1.02). Among children eligible by delay, children of mothers who were obese evidenced an increased risk for moderate-to-severe cognitive (adjusted RR 1.04 [CI 1.02-1.07]) and physical (adjusted RR 1.04 [CI 1.01-1.08]) delays and for global developmental delay (adjusted RR 1.05 [CI 1.01-1.08]). Maternal obesity is associated with increased risk of developmental delay in offspring. Among children with moderate or severe delays, maternal obesity is associated with increased risk of cognitive and physical delays as well as with increased risk for global developmental delay. While causation remains uncertain, this adds to the growing body of research reporting an association between maternal obesity and neurodevelopmental delays in offspring.

Mechanism of blood pressure and R-R variability: insights from ganglion blockade in humans

Science.gov (United States)

Zhang, Rong; Iwasaki, Kenichi; Zuckerman, Julie H.; Behbehani, Khosrow; Crandall, Craig G.; Levine, Benjamin D.; Blomqvist, C. G. (Principal Investigator)

2002-01-01

Spontaneous blood pressure (BP) and R-R variability are used frequently as 'windows' into cardiovascular control mechanisms. However, the origin of these rhythmic fluctuations is not completely understood. In this study, with ganglion blockade, we evaluated the role of autonomic neural activity versus other 'non-neural' factors in the origin of BP and R-R variability in humans. Beat-to-beat BP, R-R interval and respiratory excursions were recorded in ten healthy subjects (aged 30 +/- 6 years) before and after ganglion blockade with trimethaphan. The spectral power of these variables was calculated in the very low (0.0078-0.05 Hz), low (0.05-0.15 Hz) and high (0.15-0.35 Hz) frequency ranges. The relationship between systolic BP and R-R variability was examined by cross-spectral analysis. After blockade, R-R variability was virtually abolished at all frequencies; however, respiration and high frequency BP variability remained unchanged. Very low and low frequency BP variability was reduced substantially by 84 and 69 %, respectively, but still persisted. Transfer function gain between systolic BP and R-R interval variability decreased by 92 and 88 % at low and high frequencies, respectively, while the phase changed from negative to positive values at the high frequencies. These data suggest that under supine resting conditions with spontaneous breathing: (1) R-R variability at all measured frequencies is predominantly controlled by autonomic neural activity; (2) BP variability at high frequencies (> 0.15 Hz) is mediated largely, if not exclusively, by mechanical effects of respiration on intrathoracic pressure and/or cardiac filling; (3) BP variability at very low and low frequencies (rhythmicity; and (4) the dynamic relationship between BP and R-R variability as quantified by transfer function analysis is determined predominantly by autonomic neural activity rather than other, non-neural factors.

DNA aptamer selection and aptamer-based fluorometric displacement assay for the hepatotoxin microcystin-RR

International Nuclear Information System (INIS)

Wu, Shijia; Li, Qi; Duan, Nuo; Wang, Zhouping; Ma, Haile

2016-01-01

Microcystin-RR (MC-RR) is a highly acute hepatotoxin produced by cyanobacteria. It is harmful to both humans and the environment. A novel aptamer was identified by the systemic evolution of ligands by exponential enrichment (SELEX) method as a recognition element for determination of MC-RR in aquatic products. The graphene oxide (GO) SELEX strategy was adopted to generate aptamers with high affinity and specificity. Of the 50 aptamer candidates tested, sequence RR-33 was found to display high affinity and selectivity, with a dissociation constant of 45.7 ± 6.8 nM. Aptamer RR-33 therefore was used as the recognition element in a fluorometric assay that proceeds as follows: (1) Biotinylated aptamer RR-33 is immobilized on the streptavidinylated wells of a microtiterplate, and carboxyfluorescein (FAM) labelled complementary DNA is then allowed to hybridize. (2) After removal of excess (unbound) cDNA, sample containing MC-RR is added and incubated at 37 °C for 2 h. (3) Displaced free cDNA is washed away and fluorescence intensity measured at excitation/emission wavelengths of 490/515 nm. The calibration plot is linear in the 0.20 to 2.5 ng·mL −1 concentration range, and the limit of detection is 80 pg·mL −1 . The results indicate that the GO-SELEX technology is appropriate for the screening of aptamers against small-molecule toxins. The detection scheme was applied to the determination of MC-RR in (spiked) water, mussel and fish and gave recoveries between 91 and 98 %. The method compares favorably to a known ELISA. Conceivably, this kind of assay is applicable to other toxins for which appropriate aptamers are available. (author)

Association of Caucasian-identified variants with colorectal cancer risk in Singapore Chinese.

Directory of Open Access Journals (Sweden)

Lai Fun Thean

Full Text Available Genome-wide association studies (GWAS in Caucasians have identified fourteen index single nucleotide polymorphisms (iSNPs that influence colorectal cancer (CRC risk.We investigated the role of eleven iSNPs or surrogate SNPs (sSNPs, in high linkage disequilibrium (LD, r(2≥ 0.8 and within 100 kb vicinity of iSNPs, in 2,000 age- and gender-matched Singapore Chinese (SCH cases and controls.Only iSNP rs6983267 at 8q24.21 and sSNPs rs6695584, rs11986063, rs3087967, rs2059254, and rs7226855 at 1q41, 8q23.3, 11q23.1, 16q22.1 and 18q21.1 respectively showed evidence of association with CRC risk, with odds ratios (OR ranging from 1.13 to 1.40. sSNP rs827401 at 10p14 was associated with rectal cancer risk (OR = 0.74, 95% CI 0.63-0.88 but not disease prognosis (OR = 0.91, 95% CI 0.69-1.20. Interestingly, sSNP rs3087967 at 11q23.1 was associated with CRC risk in men (OR = 1.34, 95% CI 1.14-1.58 but not women (OR = 1.07, 95% CI: 0.88-1.29, suggesting a gender-specific role. Half of the Caucasian-identified variants, including the recently fine-mapped BMP pathway loci, BMP4, GREM1, BMP2 and LAMA 5, did not show any evidence for association with CRC in SCH (OR ~1; p-value >0.1. Comparing the results of this study with that of the Northern and Hong Kong Chinese, only variants at chromosomes 8q24.21, 10p14, 11q23.1 and 18q21.1 were replicated in at least two out of the three Chinese studies.The contrasting results between Caucasians and Chinese could be due to different LD patterns and allelic frequencies or genetic heterogeneity. The results suggest that additional common variants contributing to CRC predisposition remained to be identified.

Community-based stillbirth rates and risk factors in rural Sarlahi, Nepal.

Science.gov (United States)

Lee, Anne C; Mullany, Luke C; Tielsch, James M; Katz, Joanne; Khatry, Subarna K; Leclerq, Steven C; Adhikari, Ramesh K; Darmstadt, Gary L

2011-06-01

To assess stillbirth rates and antepartum risk factors in rural Nepal. Data were collected prospectively during a cluster-randomized, community-based trial in Sarlahi, Nepal, from 2002 to 2006. Multivariate regression modeling was performed to calculate adjusted relative risk estimates. Among 24531 births, the stillbirth rate was 35.4 per 1000 births (term stillbirth rate 21.2 per 1000 births). Most births occurred at home without a skilled birth attendant. The majority (69%) of intrapartum maternal deaths resulted in stillbirth. The adjusted RR (aRR) of stillbirth was 2.74 among nulliparas and 1.47 among mothers with history of a child death. Mothers above the age of 30 years carried a 1.59-fold higher risk for stillbirth than mothers who were 20-24 years old. The stillbirth risk was lower among households where the father had any formal education (aRR 0.70). Land ownership (aRR 0.85) and Pahadi ethnicity (aRR 0.67; reference: Madhesi ethnicity) were associated with significantly lower risks of stillbirth. Stillbirth rates were high in rural Nepal, with the majority of stillbirths occurring at full-term gestation. Nulliparity, history of prior child loss, maternal age above 30 years, Madhesi ethnicity, and socioeconomic disadvantage were significant risk factors for stillbirth. Clinicaltrials.govNCT00 109616. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Status of the Olympus experiment at CRC

Science.gov (United States)

Rogers, David V.

1992-01-01

The status of the Olympus Propagation Experiment of the Communications Research Centre in Ottawa, Canada, is briefly summarized. Path attenuation measurements at multiple frequencies correlated with concurrent dual polarized radar data provide a unique method to investigate propagation effects. An experiment of this type is being implemented by the Communications Research Centre (CRC) on the grounds of the National Research Council of Canada in Ottawa. Beacon receivers monitor signals from the Olympus satellite at 12.5, 19.77, and 29.66 GHz at a path elevation angle of 14.2 deg. Sky noise radiometers operating near the same frequencies and pointed along the same path provide additional propagation information. A colocated dual-polarized 9.6-GHz radar probes the precipitation state on the path, permitting identification of precipitation regimes that cause the observed impairments. The Olympus experiment configuration is displayed pictorially. Information on path propagation phenomena can be deduced by correlating the radar, beacon, and sky noise data. Melting layer effects and propagation losses for higher time percentages are prime interests. Data collected by Diversitel Communications during equipment verification tests are presented.

Ridge Regression and Other Kernels for Genomic Selection with R Package rrBLUP

Directory of Open Access Journals (Sweden)

Jeffrey B. Endelman

2011-11-01

Full Text Available Many important traits in plant breeding are polygenic and therefore recalcitrant to traditional marker-assisted selection. Genomic selection addresses this complexity by including all markers in the prediction model. A key method for the genomic prediction of breeding values is ridge regression (RR, which is equivalent to best linear unbiased prediction (BLUP when the genetic covariance between lines is proportional to their similarity in genotype space. This additive model can be broadened to include epistatic effects by using other kernels, such as the Gaussian, which represent inner products in a complex feature space. To facilitate the use of RR and nonadditive kernels in plant breeding, a new software package for R called rrBLUP has been developed. At its core is a fast maximum-likelihood algorithm for mixed models with a single variance component besides the residual error, which allows for efficient prediction with unreplicated training data. Use of the rrBLUP software is demonstrated through several examples, including the identification of optimal crosses based on superior progeny value. In cross-validation tests, the prediction accuracy with nonadditive kernels was significantly higher than RR for wheat ( L. grain yield but equivalent for several maize ( L. traits.

Marketing a Healthy Mind, Body, and Soul: An Analysis of How African American Men View the Church as a Social Marketer and Health Promoter of Colorectal Cancer Risk and Prevention.

Science.gov (United States)

Lumpkins, Crystal Y; Vanchy, Priya; Baker, Tamara A; Daley, Christine; Ndikum-Moffer, Florence; Greiner, K Allen

2016-08-01

The Centers for Disease Control and Prevention ranks colorectal cancer (CRC) as the third most commonly diagnosed cancer among men in the United States; African American (AA) men are at even greater risk. The present study was from a larger study that investigates the church's role as a social marketer of CRC risk and prevention messages, and whether religiously targeted and tailored health promotion materials will influence screening outcome. We used an integrated theoretical approach to explore participants' perceptions of CRC risk and prevention and how promotion messages should be developed and socially marketed by the church. Six focus groups were conducted with men from predominately AA churches in the Midwest. Themes from focus group discussions showed participants lacked knowledge about CRC, feared cancer diagnosis, and feared the procedure for screening. Roles of masculinity and the mistrust of physicians were also emergent themes. Participants did perceive the church as a trusted marketer of CRC but believed that promotional materials should be cosponsored and codeveloped by reputable health organizations. Employing the church as a social marketer of CRC screening promotion materials may be useful in guiding health promotions and addressing barriers that are distinct among African American men. © 2015 Society for Public Health Education.

TNF-α -308 A allele is associated with an increased risk of distant metastasis in rectal cancer patients from Southwestern China.

Directory of Open Access Journals (Sweden)

Zhen Li

Full Text Available Tumor necrosis factor-α (TNF-α, an important factor in systematic inflammation, is reportedly involved in several cancer types. The TNF-α -308 G>A (rs1800629 polymorphism in the promoter region influences TNF-α production. The association between TNF-α -308 G>A polymorphism and colorectal cancer (CRC is not fully understood, especially the connections between TNF-α -308 G>A polymorphism and clinical features of CRC. In this study, TNF-α -308 G>A polymorphism was genotyped in 1140 individuals with or without CRC from Southwestern China. In case-control studies, we found no association between TNF-α -308 G>A polymorphism and CRC risk. Analysis of the correlations between TNF-α -308 G>A polymorphism and clinical features of CRC revealed that TNF-α -308 A allele was associated with higher body mass index (BMI larger tumor size, and distant tumor metastasis in all CRC patients. Notably, rectal cancer (a subtype of CRC patients with TNF-α -308 A allele had a very high risk of distant tumor metastasis [odds ratio (OR = 4.481; 95% confidence interval (CI: 2.072-9.693; P = 0.00025]. The association between TNF-α -308 A allele and distant tumor metastasis remained even significant after adjusting all clinical characteristics (OR = 7.099; 95% CI: 2.482-20.301; P = 0.000256 in rectal cancer patients. Our results suggested that TNF-α -308 A allele was significantly associated with distant tumor metastasis in rectal cancer patients.

Recurrence of Subdural Haematoma in a Population-Based Cohort – Risks and Predictive Factors

Science.gov (United States)

Schmidt, Linnea; Gørtz, Sanne; Wohlfahrt, Jan; Melbye, Mads; Munch, Tina Noergaard

2015-01-01

Objectives To estimate the risks of and identify predictors for recurrent subdural haematoma in surgically and conservatively treated patients. Methods The cohort comprised all individuals diagnosed with a first-time subdural hematoma in Denmark 1996–2011. Information on potential predictors was retrieved from the Danish health registers. Cumulative recurrence risks were estimated using the Aalen-Johansen estimator. Rate ratios (RR) were estimated using Poisson regression. Results Among 10,158 individuals with a subdural hematoma, 1,555 had a recurrent event. The cumulative risk of recurrent subdural hematoma was 9% at 4 weeks after the primary bleeding, increasing to and stabilising at 14% after one year. Predictors associated with recurrence were: Male sex (RR 1.60, 95% CI:1.43–1.80), older age (>70 years compared to 20–49 years; RR 1.41, 95% CI: 1.21–1.65), alcohol addiction (RR 1.20, 95% CI:1.04–1.37), surgical treatment (RR 1.76, 95% CI:1.58–1.96), trauma diagnoses (RR 1.14, 95% CI:1.03–1.27), and diabetes mellitus (RR 1.40, 95% CI:1.11–1.74). Out of a selected combination of risk factors, the highest cumulative 1-year recurrence risks for subdural hematoma of 25% (compared to 14% for all patients) was found in surgically treated males with diabetes mellitus. Conclusions The recurrence risk of subdural hematoma is largely limited to the first year. Patient characteristics including co-morbidities greatly influence the recurrence risk of SDH, suggesting that individualized prognostic guidance and follow-up is needed. PMID:26465602

Dietary N-nitroso compounds and risk of colorectal cancer: a case-control study in Newfoundland and Labrador and Ontario, Canada

Science.gov (United States)

Zhu, Yun; Wang, Peizhong Peter; Zhao, Jing; Green, Roger; Sun, Zhuoyu; Roebothan, Barbara; Squires, Josh; Buehler, Sharon; Dicks, Elizabeth; Zhao, Jinhui; Cotterchio, Michelle; Campbell, Peter T.; Jain, Meera; Parfrey, Patrick S.; Mclaughlin, John R.

2015-01-01

Several N-nitroso compounds (NOC) have been shown to be carcinogenic in a variety of laboratory animals, but evidence of their carcinogenicity in humans is lacking. We aimed to examine the association between NOC intake and colorectal cancer (CRC) risk and possible effect modification by vitamins C and E and protein in a large case-control study carried out in Newfoundland and Labrador, and Ontario, Canada. A total of 1760 case patients with pathologically confirmed adenocarcinoma and 2481 population controls were asked to complete a self-administered FFQ to evaluate their dietary intakes 1 year before diagnosis (for cases) or interview (for controls). Adjusted OR and 95% CI were calculated across the quintiles of NOC (measured by N-nitrosodimethylamine (NDMA)) intake and relevant food items using unconditional logistic regression. NDMA intake was found to be associated with a higher risk of CRC (highest vs lowest quintiles, OR: 1.42; 95% CI: 1.03,1.96; p-trend=0.005), specifically for rectal carcinoma (OR: 1.61; 95% CI: 1.11,2.35; p-trend=0.01). CRC risk also increased with the consumption of NDMA-containing meats when the highest tertile was compared with the lowest tertile (OR: 1.47; 95% CI: 1.03,2.10; p-trend=0.20). There was evidence of effect modification between dietary vitamin E and NDMA. Individuals with high NDMA and low vitamin E intakes had a significantly increased risk than those with both low NDMA and vitamin E intakes (OR:3.01; 95% CI: 1.43,6.51; p-interaction=0.017). The present results support the hypothesis that NOC intake may be positively associated with CRC risk in humans. Vitamin E, which inhibits nitrosation, could modify the effect of NDMA on CRC risk. PMID:24160559

Adipose tissue (P)RR regulates insulin sensitivity, fat mass and body weight.

Science.gov (United States)

Shamansurova, Zulaykho; Tan, Paul; Ahmed, Basma; Pepin, Emilie; Seda, Ondrej; Lavoie, Julie L

2016-10-01

We previously demonstrated that the handle-region peptide, a prorenin/renin receptor [(P)RR] blocker, reduces body weight and fat mass and may improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking out the adipose tissue (P)RR gene would prevent weight gain and insulin resistance. An adipose tissue-specific (P)RR knockout (KO) mouse was created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (P)RR gene is located on the X chromosome, hemizygous males were complete KO and had a more pronounced phenotype on a normal diet (ND) diet compared to heterozygous KO females. Therefore, we challenged the female mice with a high-fat diet (HFD) to uncover certain phenotypes. Mice were maintained on either diet for 9 weeks. KO mice had lower body weights compared to wild-types (WT). Only hemizygous male KO mice presented with lower total fat mass, higher total lean mass as well as smaller adipocytes compared to WT mice. Although food intake was similar between genotypes, locomotor activity during the active period was increased in both male and female KO mice. Interestingly, only male KO mice had increased O2 consumption and CO2 production during the entire 24-hour period, suggesting an increased basal metabolic rate. Although glycemia during a glucose tolerance test was similar, KO males as well as HFD-fed females had lower plasma insulin and C-peptide levels compared to WT mice, suggesting improved insulin sensitivity. Remarkably, all KO animals exhibited higher circulating adiponectin levels, suggesting that this phenotype can occur even in the absence of a significant reduction in adipose tissue weight, as observed in females and, thus, may be a specific effect related to the (P)RR. (P)RR may be an important therapeutic target for the treatment of obesity and its associated complications such as type 2 diabetes.

DISTANCE SCALE ZERO POINTS FROM GALACTIC RR LYRAE STAR PARALLAXES

Energy Technology Data Exchange (ETDEWEB)

Benedict, G. Fritz; McArthur, Barbara E.; Barnes, Thomas G. [McDonald Observatory, University of Texas, Austin, TX 78712 (United States); Feast, Michael W. [Centre for Astrophysics, Cosmology and Gravitation, Astronomy Department, University of Cape Town, Rondebosch 7701 (South Africa); Harrison, Thomas E. [Department of Astronomy, New Mexico State University, Las Cruces, NM 88003 (United States); Bean, Jacob L.; Kolenberg, Katrien [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Menzies, John W.; Laney, C. D. [South African Astronomical Observatory, Observatory 7935 (South Africa); Chaboyer, Brian [Department of Physics and Astronomy, Dartmouth College, Hanover, NH 03755 (United States); Fossati, Luca [Department of Physics and Astronomy, Open University, Milton Keynes MK7 6AA (United Kingdom); Nesvacil, Nicole [Institute of Astronomy, University of Vienna, A-1180 Vienna (Austria); Smith, Horace A. [Department of Physics and Astronomy, Michigan State University, East Lansing, MI 48824 (United States); Kochukhov, Oleg [Department of Physics and Astronomy, Uppsala University, 75120 Uppsala (Sweden); Nelan, Edmund P.; Taylor, Denise [STScI, Baltimore, MD 21218 (United States); Shulyak, D. V. [Institute of Astrophysics, Georg-August-University, Friedrich-Hund-Platz 1, D-37077 Goettingen (Germany); Freedman, Wendy L. [The Observatories, Carnegie Institution of Washington, Pasadena, CA 91101 (United States)

2011-12-15

We present new absolute trigonometric parallaxes and proper motions for seven Population II variable stars-five RR Lyr variables: RZ Cep, XZ Cyg, SU Dra, RR Lyr, and UV Oct; and two type 2 Cepheids: VY Pyx and {kappa} Pav. We obtained these results with astrometric data from Fine Guidance Sensors, white-light interferometers on Hubble Space Telescope. We find absolute parallaxes in milliseconds of arc: RZ Cep, 2.12 {+-} 0.16 mas; XZ Cyg, 1.67 {+-} 0.17 mas; SU Dra, 1.42 {+-} 0.16 mas; RR Lyr, 3.77 {+-} 0.13 mas; UV Oct, 1.71 {+-} 0.10 mas; VY Pyx, 6.44 {+-} 0.23 mas; and {kappa} Pav, 5.57 {+-} 0.28 mas; an average {sigma}{sub {pi}}/{pi} = 5.4%. With these parallaxes, we compute absolute magnitudes in V and K bandpasses corrected for interstellar extinction and Lutz-Kelker-Hanson bias. Using these RR Lyrae variable star absolute magnitudes, we then derive zero points for M{sub V} -[Fe/H] and M{sub K} -[Fe/H]-log P relations. The technique of reduced parallaxes corroborates these results. We employ our new results to determine distances and ages of several Galactic globular clusters and the distance of the Large Magellanic Cloud. The latter is close to that previously derived from Classical Cepheids uncorrected for any metallicity effect, indicating that any such effect is small. We also discuss the somewhat puzzling results obtained for our two type 2 Cepheids.

Estrogen Metabolites Are Not Associated With Colorectal Cancer Risk In Postmenopausal Women

Science.gov (United States)

Falk, Roni T.; Dallal, Cher M.; Lacey, James V.; Bauer, Douglas C.; Buist, Diana SM; Cauley, Jane A.; Hue, Trisha F.; LaCroix, Andrea; Tice, Jeffrey A.; Pfeiffer, Ruth M.; Xu, Xia; Veenstra, Timothy D.; Brinton, Louise A.

2015-01-01

Background A potential protective role for estrogen in colon carcinogenesis has been suggested based on exogenous hormone use, but it is unclear from previous studies whether endogenous estrogens are related to colorectal cancer (CRC) risk. These few prior studies focused on parent estrogens; none evaluated effects of estrogen metabolism in postmenopausal women. Methods We followed 15,595 women (ages 55–80) enrolled in B~FIT (Breast and Bone Follow-up to the Fracture Intervention Trial (FIT)) who donated blood between 1992 and 1993 for cancer through December 2004. A panel of 15 estrogen metabolites (EM), including estradiol and estrone, were measured in serum from 187 CRC cases and a subcohort of 501 women not using exogenous hormones at blood draw. We examined EM individually, grouped by pathway (hydroxylation at the C-2, C-4, or C-16 position), and by ratios of the groupings using Cox proportional hazards regression models. Results No significant associations were seen for estrone (HRQ4 v Q1=1.15, 95% CI=0.69–1.93, ptrend=0.54), estradiol (HRQ4 v Q1= 0.98, 95% CI=0.58–1.64, ptrend>0.99) or total EM (the sum of all EM; HRQ4 v Q1=1.35. 95% CI=0.81–2.24, ptrend=0.33). Most metabolites in the 2-, 4- or 16-pathway were unrelated to risk, although a borderline trend in risk was associated with high levels of 17-epiestriol. Conclusion Circulating estrogens and their metabolites were generally unrelated to CRC risk in postmenopausal women. Impact Additional studies are needed to understand how exogenous estrogen may prevent CRC PMID:26104910

Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: The ESCARVAL-RISK study.

Science.gov (United States)

Orozco-Beltran, Domingo; Gil-Guillen, Vicente F; Redon, Josep; Martin-Moreno, Jose M; Pallares-Carratala, Vicente; Navarro-Perez, Jorge; Valls-Roca, Francisco; Sanchis-Domenech, Carlos; Fernandez-Gimenez, Antonio; Perez-Navarro, Ana; Bertomeu-Martinez, Vicente; Bertomeu-Gonzalez, Vicente; Cordero, Alberto; Pascual de la Torre, Manuel; Trillo, Jose L; Carratala-Munuera, Concepcion; Pita-Fernandez, Salvador; Uso, Ruth; Durazo-Arvizu, Ramon; Cooper, Richard; Sanz, Gines; Castellano, Jose M; Ascaso, Juan F; Carmena, Rafael; Tellez-Plaza, Maria

2017-01-01

The potential impact of targeting different components of an adverse lipid profile in populations with multiple cardiovascular risk factors is not completely clear. This study aims to assess the association between different components of the standard lipid profile with all-cause mortality and hospitalization due to cardiovascular events in a high-risk population. This prospective registry included high risk adults over 30 years old free of cardiovascular disease (2008-2012). Diagnosis of hypertension, dyslipidemia or diabetes mellitus was inclusion criterion. Lipid biomarkers were evaluated. Primary endpoints were all-cause mortality and hospital admission due to coronary heart disease or stroke. We estimated adjusted rate ratios (aRR), absolute risk differences and population attributable risk associated with adverse lipid profiles. 51,462 subjects were included with a mean age of 62.6 years (47.6% men). During an average follow-up of 3.2 years, 919 deaths, 1666 hospitalizations for coronary heart disease and 1510 hospitalizations for stroke were recorded. The parameters that showed an increased rate for total mortality, coronary heart disease and stroke hospitalization were, respectively, low HDL-Cholesterol: aRR 1.25, 1.29 and 1.23; high Total/HDL-Cholesterol: aRR 1.22, 1.38 and 1.25; and high Triglycerides/HDL-Cholesterol: aRR 1.21, 1.30, 1.09. The parameters that showed highest population attributable risk (%) were, respectively, low HDL-Cholesterol: 7.70, 11.42, 8.40; high Total/HDL-Cholesterol: 6.55, 12.47, 8.73; and high Triglycerides/HDL-Cholesterol: 8.94, 15.09, 6.92. In a population with cardiovascular risk factors, HDL-cholesterol, Total/HDL-cholesterol and triglycerides/HDL-cholesterol ratios were associated with a higher population attributable risk for cardiovascular disease compared to other common biomarkers.

Quality control of the NPL-CRC secondary standard system used for activimeters calibration at IPEN, Sao Paulo, Brazil

International Nuclear Information System (INIS)

Martins, Elaine W.; Potiens, Maria da P.A.

2009-01-01

The objective of this study was to establish a quality control program to be applied at the NPL-CRC activimeter secondary standard system, used as reference to comparison in tests made with the work tertiary standard activimeter, Capintec basic CRC R -15BT, both belonging to the Calibration Laboratory of IPEN. The repeatability, reproducibility and the precision tests were performed using a sealed check source of 133 Ba, from Amersham. It was made 70 series of 10 measurements to each activimeter, totaling 1400 measurements. Considering the variation limit of 5% to precision and reproducibility tests in the nuclear medicine services, recommended by the Brazilian standard CNEN-NN-3.05, the results observed in the behavior of the IPEN activimeter were satisfactory. (author)

CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 4 AND 5 OF CRYSTAL RIVER UNIT 3

International Nuclear Information System (INIS)

Wright, Kenneth D.

1997-01-01

The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 4 and 5 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies

Preeclampsia: at risk for remote cardiovascular disease

NARCIS (Netherlands)

Harskamp, Ralf E.; Zeeman, Gerda G.

2007-01-01

Epidemiological data indicate that women with preeclampsia are more likely to develop cardiovascular disease (CVD) later in life. Population-based studies relate preeclampsia to an increased risk of later chronic hypertension (RR, 2.00 to 8.00) and cardiovascular morbidity/mortality (RR, 1.3 to

Preeclampsia : At risk for remote cardiovascular disease

NARCIS (Netherlands)

Harskamp, Ralf E.; Zeeman, Gerda G.

2007-01-01

Epidemiological data indicate that women with preeclampsia are more likely to develop cardiovascular disease (CVD) later in life. Population-based studies relate preeclampsia to an increased risk of later chronic hypertension (RR, 2.00 to 8.00) and cardiovascular morbidity/mortality (RR, 1.3 to

Nonlinear Convective Models of RR Lyrae Stars

Science.gov (United States)

Feuchtinger, M.; Dorfi, E. A.

The nonlinear behavior of RR Lyrae pulsations is investigated using a state-of-the-art numerical technique solving the full time-dependent system of radiation hydrodynamics. Grey radiative transfer is included by a variable Eddington-factor method and we use the time-dependent turbulent convection model according to Kuhfuss (1986, A&A 160, 116) in the version of Wuchterl (1995, Comp. Phys. Comm. 89, 19). OPAL opacities extended by the Alexander molecule opacities at temperatures below 6000 K and an equation of state according to Wuchterl (1990, A&A 238, 83) close the system. The resulting nonlinear system is discretized on an adaptive mesh developed by Dorfi & Drury (1987, J. Comp. Phys. 69, 175), which is important to provide the necessary spatial resolution in critical regions like ionization zones and shock waves. Additionally, we employ a second order advection scheme, a time centered temporal discretizaton and an artificial tensor viscosity in order to treat discontinuities. We compute fundamental as well first overtone models of RR Lyrae stars for a grid of stellar parameters both with and without convective energy transport in order to give a detailed picture of the pulsation-convection interaction. In order to investigate the influence of the different features of the convection model calculations with and without overshooting, turbulent pressure and turbulent viscosity are performed and compared with each other. A standard Fourier decomposition is used to confront the resulting light and radial velocity variations with recent observations and we show that the well known RR Lyrae phase discrepancy problem (Simon 1985, ApJ 299, 723) can be resolved with these stellar pulsation computations.

The Int7G24A variant of transforming growth factor-beta receptor type I is a risk factor for colorectal cancer in the male Spanish population: a case-control study

Directory of Open Access Journals (Sweden)

Lázaro Rafael

2009-11-01

Full Text Available Abstract Background The Int7G24A variant of transforming growth factor-beta receptor type I (TGFBR1 has been shown to increase the risk for kidney, ovarian, bladder, lung and breast cancers. Its role in colorectal cancer (CRC has not been established. The aims of this study were to assess the association of TGFBR1*Int7G24A variant with CRC occurrence, patient age, gender, tumour location and stage. Methods We performed a case-control study with 504 cases of sporadic CRC; and 504 non-cancerous age, gender and ethnically matched controls. Genotyping analysis was performed using allelic discrimination assay by real time PCR. Results The Int7G24A variant was associated with increased CRC incidence in an additive model of inheritance (P for trend = 0.005. No significant differences were found between Int7G24A genotypes and tumour location or stage. Interestingly, the association of the Int7G24A variant with CRC risk was significant in men (odds ratio 4.10 with 95% confidence intervals 1.41-11.85 for homozygous individuals; P for trend = 0.00023, but not in women. We also observed an increase in susceptibility to CRC for individuals aged less than 70 years. Conclusion Our data suggest that the Int7G24A variant represents a risk factor for CRC in the male Spanish population.

The VMC survey - XXVI. Structure of the Small Magellanic Cloud from RR Lyrae stars

Science.gov (United States)

Muraveva, T.; Subramanian, S.; Clementini, G.; Cioni, M.-R. L.; Palmer, M.; van Loon, J. Th.; Moretti, M. I.; de Grijs, R.; Molinaro, R.; Ripepi, V.; Marconi, M.; Emerson, J.; Ivanov, V. D.

2018-01-01

We present results from the analysis of 2997 fundamental mode RR Lyrae variables located in the Small Magellanic Cloud (SMC). For these objects, near-infrared time series photometry from the VISTA survey of the Magellanic Clouds system (VMC) and visual light curves from the OGLE IV (Optical Gravitational Lensing Experiment IV) survey are available. In this study, the multi-epoch Ks-band VMC photometry was used for the first time to derive intensity-averaged magnitudes of the SMC RR Lyrae stars. We determined individual distances to the RR Lyrae stars from the near-infrared period-absolute magnitude-metallicity (PM_{K_s}Z) relation, which has some advantages in comparison with the visual absolute magnitude-metallicity (MV-[Fe/H]) relation, such as a smaller dependence of the luminosity on interstellar extinction, evolutionary effects and metallicity. The distances we have obtained were used to study the three-dimensional structure of the SMC. The distribution of the SMC RR Lyrae stars is found to be ellipsoidal. The actual line-of-sight depth of the SMC is in the range 1-10 kpc, with an average depth of 4.3 ± 1.0 kpc. We found that RR Lyrae stars in the eastern part of the SMC are affected by interactions of the Magellanic Clouds. However, we do not see a clear bimodality observed for red clump stars, in the distribution of RR Lyrae stars.

First Kepler Results on RR Lyrae Stars

DEFF Research Database (Denmark)

Kolenberg, K.; Szabó, R.; Kurtz, D. W.

2010-01-01

We present the first results of our analyses of selected RR Lyrae stars for which data have been obtained by the Kepler Mission. As expected, we find a significant fraction of the RRab stars to show the Blazhko effect, a still unexplained phenomenon that manifests itself as periodic amplitude and...

Dietary Intake of Meat Cooking-Related Mutagens (HCAs) and Risk of Colorectal Adenoma and Cancer: A Systematic Review and Meta-Analysis

OpenAIRE

Chiavarini, Manuela; Bertarelli, Gaia; Minelli, Liliana; Fabiani, Roberto

2017-01-01

Much evidence suggests that the positive association between meat intake and colorectal adenoma (CRA) and cancer (CRC) risk is mediated by mutagenic compounds generated during cooking at high temperature. A number of epidemiological studies have estimated the effect of meat-related mutagens intake on CRC/CRA risk with contradictory and sometimes inconsistent results. A literature search was carried out (PubMed, Web of Science and Scopus) to identify articles reporting the relationship between...

Lignification of the plant and seed quality of RR soybeans sprayed with herbicide glyphosate

OpenAIRE

Gris,Cristiane Fortes; Pinho,Edila Vilela de Resende Von; Carvalho,Maria Laene de Moreira; Diniz,Rafael Parreira; Andrade,Thaís de

2013-01-01

Differences in levels of lignin in the plant between conventional and transgenic cultivars RR has been reported by several authors, however, there are few studies evaluating the influence of spraying of glyphosate on the lignin in the plant and RR soybean seeds. The aim of this study was to evaluate the physiological quality of RR transgenic soybean seeds and the lignin contents of plants sprayed with the herbicide glyphosate. The assays were conducted both in greenhouse and field in the muni...

Risk factors for teenage pregnancy among sexually active black ...

African Journals Online (AJOL)

... with 191 cases and 353 age-matched controls from the same school or neighbourhood. ... sex (risk ratio (RR) 30.81) without reliable contraceptive protection (RR 24.35), ... and broader social development and promotion of gender equality.

Characterization of the VVV Survey RR Lyrae Population across the Southern Galactic Plane

International Nuclear Information System (INIS)

Minniti, Dante; Palma, Tali; Pullen, Joyce; Tissera, Patricia; Dékány, Istvan; Majaess, Daniel; Rejkuba, Marina; Valenti, Elena; Alonso-García, Javier; Catelan, Marcio; Contreras Ramos, Rodrigo; Zoccali, Manuela; Gonzalez, Oscar A.; Hempel, Maren; Irwin, Mike; Lucas, Philip W.; Saito, Roberto K.

2017-01-01

Deep near-IR images from the VISTA Variables in the Vía Láctea (VVV) Survey were used to search for RR Lyrae stars in the Southern Galactic plane. A sizable sample of 404 RR Lyrae of type ab stars was identified across a thin slice of the fourth Galactic quadrant (295° < ℓ < 350°, −2.°24 < b < −1.°05). The sample’s distance distribution exhibits a maximum density that occurs at the bulge tangent point, which implies that this primarily Oosterhoff type I population of RRab stars does not trace the bar delineated by their red clump counterparts. The bulge RR Lyrae population does not extend beyond ℓ  ∼ 340°, and the sample’s spatial distribution presents evidence of density enhancements and substructure that warrants further investigation. Indeed, the sample may be employed to evaluate Galactic evolution models, and is particularly lucrative since half of the discovered RR Lyrae are within reach of Gaia astrometric observations.

Characterization of the VVV Survey RR Lyrae Population across the Southern Galactic Plane

Energy Technology Data Exchange (ETDEWEB)

Minniti, Dante; Palma, Tali; Pullen, Joyce; Tissera, Patricia [Departamento de Ciencias Físicas, Facultad de Ciencias Exactas, Universidad Andrés Bello, Av. Fernández Concha 700, Las Condes, Santiago (Chile); Dékány, Istvan [Astronomisches Rechen-Institut, Zentrum fuer Astronomie der Universitaet Heidelberg, Moenchhofstr. 12-14, D-69120 Heidelberg (Germany); Majaess, Daniel [Mount Saint Vincent University, Halifax, Nova Scotia (Canada); Rejkuba, Marina; Valenti, Elena [European Southern Observatory, Karl-Schwarszchild-Str. 2, D-85748 Garching bei Muenchen (Germany); Alonso-García, Javier; Catelan, Marcio; Contreras Ramos, Rodrigo; Zoccali, Manuela [Instituto Milenio de Astrofísica, Santiago (Chile); Gonzalez, Oscar A. [Institute for Astronomy, University of Edinburgh, Royal Observatory, Blackford Hill, Edinburgh, EH9 3HJ (United Kingdom); Hempel, Maren [Pontificia Universidad Católica de Chile, Instituto de Astrofisica, Av. Vicuna Mackenna 4860, Santiago (Chile); Irwin, Mike [Institute of Astronomy, Cambridge University, Cambridge, CB3 0HA (United Kingdom); Lucas, Philip W. [Department of Astronomy, University of Hertfordshire, Hertfordshire (United Kingdom); Saito, Roberto K. [Departamento de Física, Universidade Federal de Santa Catarina, Trindade 88040-900, Florianópolis, SC (Brazil)

2017-04-01

Deep near-IR images from the VISTA Variables in the Vía Láctea (VVV) Survey were used to search for RR Lyrae stars in the Southern Galactic plane. A sizable sample of 404 RR Lyrae of type ab stars was identified across a thin slice of the fourth Galactic quadrant (295° < ℓ < 350°, −2.°24 < b < −1.°05). The sample’s distance distribution exhibits a maximum density that occurs at the bulge tangent point, which implies that this primarily Oosterhoff type I population of RRab stars does not trace the bar delineated by their red clump counterparts. The bulge RR Lyrae population does not extend beyond ℓ  ∼ 340°, and the sample’s spatial distribution presents evidence of density enhancements and substructure that warrants further investigation. Indeed, the sample may be employed to evaluate Galactic evolution models, and is particularly lucrative since half of the discovered RR Lyrae are within reach of Gaia astrometric observations.

Genetic divergence of roundup ready (RR) soybean cultivars ...

African Journals Online (AJOL)

The aim of this study was to estimate the genetic diversity in 74 RR soybean cultivars from different Brazilian breeding programs. ... chosen SSR markers were effective in assessing the genetic diversity among genotypes, besides proving to be ...

Colonic polyps: inheritance, susceptibility, risk evaluation, and diagnostic management

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Emanuele Neri

2010-12-01

Full Text Available Emanuele Neri, Lorenzo Faggioni, Lorenzo Cini, Carlo BartolozziDiagnostic and Interventional Radiology, University of Pisa, Pisa, ItalyAbstract: Colorectal cancer (CRC is the third-ranked neoplasm in order of incidence and mortality, worldwide, and the second cause of cancer death in industrialized countries. One of the most important environmental risk factors for CRC is a Western-type diet, which is characterized by a low-fiber and high-fat content. Up to 25% of patients with CRC have a family history for CRC, and a fraction of these patients are affected by hereditary syndromes, such as familial adenomatous polyposis, Gardner or Turcot syndromes, or hereditary nonpolyposis colorectal cancer. The onset of CRC is triggered by a well-defined combination of genetic alterations, which form the bases of the adenoma-carcinoma sequence hypothesis and justify the set-up of CRC screening techniques. Several screening and diagnostic tests for CRC are illustrated, including rectosigmoidoscopy, optical colonoscopy (OC, double contrast barium enema (DCBE, and computed tomography colonography (CTC. The strengths and weaknesses of each technique are discussed. Particular attention is paid to CTC, which has evolved from an experimental technique to an accurate and mature diagnostic approach, and gained wide acceptance and clinical validation for CRC screening. This success of CTC is due mainly to its ability to provide cross-sectional analytical images of the entire colon and secondarily detect extracolonic findings, with minimal invasiveness and lower cost than OC, and with greater detail and diagnostic accuracy than DCBE. Moreover, especially with the advent and widespread availability of modern multidetector CT scanners, excellent quality 2D and 3D reconstructions of the large bowel can be obtained routinely with a relatively low radiation dose. Computer-aided detection systems have also been developed to assist radiologists in reading CTC examinations

Water-contact patterns and risk factors for Schistosoma mansoni infection in a rural village of Northeast Brazil

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SILVA Antônio Augusto Moura da

1997-01-01

Full Text Available Schistosomiasis mansoni in the Serrano village, municipality of Cururupu, state of Maranhão, Brazil, is a widely spread disease. The PECE (Program for the Control of Schistosomiasis, undertaken since 1979 has reduced the prevalence of S. mansoni infection and the hepatosplenic form of the disease. Nevertheless piped water is available in 84% of the households, prevalence remains above 20%. In order to identify other risk factors responsible for the persistence of high prevalence levels, a cross-sectional survey was carried out in a systematic sample of 294 people of varying ages. Socioeconomic, environmental and demographic variables, and water contact patterns were investigated. Fecal samples were collected and analyzed by the Kato-Katz technique. Prevalence of S. mansoni infection was 24.1%, higher among males (35.5% and between 10-19 years of age (36.6%. The risk factors identified in the univariable analysis were water contacts for vegetable extraction (Risk Ratio - RR = 2.92, crossing streams (RR = 2.55, bathing (RR = 2.35, fishing (RR = 2.19, hunting (RR = 2.17, cattle breeding (RR = 2.04, manioc culture (RR = 1.90 and leisure (RR = 1.56. After controlling for confounding variables by proportional hazards model the risks remained higher for males, vegetable extraction, bathing in rivers and water contact in rivers or in periodically inundated parts of riverine woodland (swamplands

[The characteristics of RR-Lorenz plot in persistent atrial fibrillation patients complicating with escape beats and rhythm].

Science.gov (United States)

Pan, Yunping; Zhang, Fangfang; Liu, Ru; Jing, Yan; Shen, Jihong; Li, Zhongjian; Zhu, Huaijie

2014-06-01

To explore the characteristics of RR-Lorenz plot in persistent atrial fibrillation (AF) patients complicating with escape beats and rhythm though ambulatory electrocardiogram. The 24-hour ambulatory electrocardiogram of 291 persistent AF patients in second affiliated hospital of Zhengzhou university from July 2005 to April 2013 were retrospectively analyzed and the RR interval and the QRS wave were measured. Patients were divided into two groups according to the distribution of the RR-Lorenz point [AF without escape beats and rhythm group (Group A, n = 259) and AF with escape beats and rhythm group (Group B, n = 32)]. The characteristics of RR-Lorenz plot between the two groups were compared. (1) Fan-shaped RR-Lorenz plots were evidenced in Group A. (2)In Group B, 30 cases showed fan-shaped with L-shaped and a short dense rods along 45° line. The proportion of escape beats and rhythm was 0.28% (275/98 369) -14.06% (11 263/80 112) . The other 2 cases in group B showed no typical RR-Lorenz plots features. RR-Lorenz plot could help to quickly diagnose persistent AF complicating with escape beats and rhythm according to the typical RR-Lorenz plot characteristics in 24-hour ambulatory electrocardiogram.

Combination of diabetes risk factors and hepatic steatosis in Chinese: the Cardiometabolic Risk in Chinese (CRC Study.

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Jun Liang

Full Text Available Hepatic steatosis has been related to insulin resistance and increased diabetes risk. We assessed whether combination of diabetes risk factors, evaluated by the Finnish Diabetes Risk Score, was associated with risk of hepatic steatosis in an apparently healthy Chinese population.The study samples were from a community-based health examination survey in central China. In total 1,780 men and women (18-64 y were included in the final analyses. Hepatic steatosis was diagnosed by ultrasonography. We created combination of diabetes risk factors score on basis of age, Body Mass Index, waist circumference, physical activity at least 4 h a week, daily consumption of fruits, berries or vegetables, history of antihypertensive drug treatment, history of high blood glucose. The total risk score is a simple sum of the individual weights, and values range from 0 to 20.Hepatic steatosis was present 18% in the total population. In multivariate models, the odds ratios of hepatic steatosis were 1.20 (95%CI 1.15-1.25 in men and 1.25 (95%CI 1.14-1.37 in women by each unit increase in the combination of diabetes risk factors score, after adjustment for blood pressure, liver enzymes, plasma lipids, and fasting glucose. The area under the receiver operating characteristic curve for hepatic steatosis was 0.78 (95%CI 0.76-0.80, 0.76 in men (95%CI 0.74-0.78 and 0.83 (95%CI 0.79-0.87 in women.Our data suggest that combination of major diabetes risk factors was significantly related to risk of hepatic steatosis in Chinese adults.

Colorectal cancer screening of high-risk populations: A national survey of physicians

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White Pascale M

2012-01-01

Full Text Available Abstract Background The incidence of colorectal cancer can be decreased by appropriate use of screening modalities. Patients with a family history of colon cancer and of African-American ethnicity are known to be at higher risk of developing colorectal cancer. We aimed to determine if there is a lack of physician knowledge for colorectal cancer screening guidelines based on family history and ethnicity. Between February and April 2009 an anonymous web-based survey was administered to a random sample selected from a national list of 25,000 internists, family physicians and gastroenterologists. A stratified sampling strategy was used to include practitioners from states with high as well as low CRC incidence. All data analyses were performed following data collection in 2009. Results The average knowledge score was 37 ± 18% among the 512 respondents. Gastroenterologists averaged higher scores compared to internists, and family physicians, p = 0.001. Only 28% of physicians correctly identified the screening initiation point for African-Americans while only 12% of physicians correctly identified the screening initiation point and interval for a patient with a family history of CRC. The most commonly cited barriers to referring high-risk patients for CRC screening were "patient refusal" and "lack of insurance reimbursement." Conclusions There is a lack of knowledge amongst physicians of the screening guidelines for high-risk populations, based on family history and ethnicity. Educational programs to improve physician knowledge and to reduce perceived barriers to CRC screening are warranted to address health disparities in colorectal cancer.

Allelic variation at the 8q23.3 colorectal cancer risk locus functions as a cis-acting regulator of EIF3H.

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Alan M Pittman

2010-09-01

Full Text Available Common genetic variation at human 8q23.3 is significantly associated with colorectal cancer (CRC risk. To elucidate the basis of this association we compared the frequency of common variants at 8q23.3 in 1,964 CRC cases and 2,081 healthy controls. Reporter gene studies showed that the single nucleotide polymorphism rs16888589 acts as an allele-specific transcriptional repressor. Chromosome conformation capture (3C analysis demonstrated that the genomic region harboring rs16888589 interacts with the promoter of gene for eukaryotic translation initiation factor 3, subunit H (EIF3H. We show that increased expression of EIF3H gene increases CRC growth and invasiveness thereby providing a biological mechanism for the 8q23.3 association. These data provide evidence for a functional basis for the non-coding risk variant rs16888589 at 8q23.3 and provides novel insight into the etiological basis of CRC.

A HIGH-VELOCITY BULGE RR LYRAE VARIABLE ON A HALO-LIKE ORBIT

International Nuclear Information System (INIS)

Kunder, Andrea; Storm, J.; Rich, R. M.; Hawkins, K.; Poleski, R.; Johnson, C. I.; Shen, J.; Li, Z.-Y.; Cordero, M. J.; Nataf, D. M.; Bono, G.; Walker, A. R.; Koch, A.; De Propris, R.; Udalski, A.; Szymanski, M. K.; Soszynski, I.; Pietrzynski, G.; Ulaczyk, K.; Wyrzykowski, Ł.

2015-01-01

We report on the RR Lyrae variable star, MACHO 176.18833.411, located toward the Galactic bulge and observed within the data from the ongoing Bulge RR Lyrae Radial Velocity Assay, which has the unusual radial velocity of −372 ± 8 km s −1 and true space velocity of −482 ± 22 km s −1 relative to the Galactic rest frame. Located less than 1 kpc from the Galactic center and toward a field at (l, b) = (3, −2.5), this pulsating star has properties suggesting it belongs to the bulge RR Lyrae star population, yet a velocity indicating it is abnormal, at least with respect to bulge giants and red clump stars. We show that this star is most likely a halo interloper and therefore suggest that halo contamination is not insignificant when studying metal-poor stars found within the bulge area, even for stars within 1 kpc of the Galactic center. We discuss the possibility that MACHO 176.18833.411 is on the extreme edge of the bulge RR Lyrae radial velocity distribution, and also consider a more exotic scenario in which it is a runaway star moving through the Galaxy

Proteomic profiling of a mouse model of acute intestinal Apc deletion leads to identification of potential novel biomarkers of human colorectal cancer (CRC).

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Hammoudi, Abeer; Song, Fei; Reed, Karen R; Jenkins, Rosalind E; Meniel, Valerie S; Watson, Alastair J M; Pritchard, D Mark; Clarke, Alan R; Jenkins, John R

2013-10-25

Colorectal cancer (CRC) is the fourth most common cause of cancer-related death worldwide. Accurate non-invasive screening for CRC would greatly enhance a population's health. Adenomatous polyposis coli (Apc) gene mutations commonly occur in human colorectal adenomas and carcinomas, leading to Wnt signalling pathway activation. Acute conditional transgenic deletion of Apc in murine intestinal epithelium (AhCre(+)Apc(fl)(/)(fl)) causes phenotypic changes similar to those found during colorectal tumourigenesis. This study comprised a proteomic analysis of murine small intestinal epithelial cells following acute Apc deletion to identify proteins that show altered expression during human colorectal carcinogenesis, thus identifying proteins that may prove clinically useful as blood/serum biomarkers of colorectal neoplasia. Eighty-one proteins showed significantly increased expression following iTRAQ analysis, and validation of nine of these by Ingenuity Pathaway Analysis showed they could be detected in blood or serum. Expression was assessed in AhCre(+)Apc(fl)(/)(fl) small intestinal epithelium by immunohistochemistry, western blot and quantitative real-time PCR; increased nucelolin concentrations were also detected in the serum of AhCre(+)Apc(fl)(/)(fl) and Apc(Min)(/)(+) mice by ELISA. Six proteins; heat shock 60kDa protein 1, Nucleolin, Prohibitin, Cytokeratin 18, Ribosomal protein L6 and DEAD (Asp-Glu-Ala-Asp) box polypeptide 5,were selected for further investigation. Increased expression of 4 of these was confirmed in human CRC by qPCR. In conclusion, several novel candidate biomarkers have been identified from analysis of transgenic mice in which the Apc gene was deleted in the intestinal epithelium that also showed increased expression in human CRC. Some of these warrant further investigation as potential serum-based biomarkers of human CRC. Copyright © 2013 Elsevier Inc. All rights reserved.

Methylenetetrahydrofolate reductase gene polymorphisms and the risk of colorectal carcinoma in a sample of Egyptian individuals.

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El Awady, Mostafa K; Karim, Amr M; Hanna, Laila S; El Husseiny, Lamia A; El Sahar, Medhat; Menem, Hanan A Abdel; Meguid, Nagwa A

2009-01-01

The study was planned as a pilot study to investigate two common polymorphisms in the MTHFR gene c.677C > T and c.1298A > C and their association with enhanced risk of colorectal cancer (CRC) in a sample of Egyptian individuals. Venous blood samples were withdrawn from 35 cases of CRC and 68 healthy controls. Specimens from colonic and rectal carcinoma tissues in addition to cancer free tissues were obtained from all cases. Frequencies of MTHFR677T and 1298C alleles were significantly higher among cases of CRC tumor tissues (50% and 56%, respectively) than germ line alleles in CRC patients (33% and 41%, respectively) and healthy controls (21% and 35%, respectively). Frequencies of heterozygous and homoyzgous polymorphisms of MTHFR at positions 677 and 1298 in carcinoma tissues were always the highest. At position 677, TT and CT genotype frequencies were 17% and 66% with an odds ratio {OR} of 11 [95% confidence interval {CI} 2.39-50.59] and OR 8.34 [95%CI 2.97-23.92], respectively, in carcinoma tissues. While in the germ line of patients the genotype frequencies of 677TT and CT were 6% and 54% with OR 1.57 [95%CI 0.26-9.51] and 2.99 [95%CI 1.25-7.12], respectively, compared to controls (6% and 29%, respectively). The combined genotype MTHFR 1298CC + AC frequencies were 86% with OR 3.71 [95%CI 1.28-10.78] in carcinoma tissues, 69% with OR 1.35 [95%CI 0.57-3.21] in germ line of patients and 62% in controls. The combined genotype 677CT plus any of the following genotypes 1298AA, AC or CC enhanced risk of CRC, when comparing germ line DNA polymorphism of patients versus peripheral blood DNA of control subjects with OR 4.5 [95%CI 0.94-21.56], OR 3.12 [95%CI 0.79-12.36] and OR 18 [95%CI 1.56-207.5], respectively, suggesting strong genetic predisposition of certain Egyptian population to CRC. These results suggested that at least one C to T polymorphism at 677MTHFR gene is required to significantly increase the risk for CRC development. Further large scale studies are

CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 4 AND 5 OF CRYSTAL RIVER UNIT 3

Energy Technology Data Exchange (ETDEWEB)

Kenneth D. Wright

1997-07-30

The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 4 and 5 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies.

Conditional Risk of Relapse in Surveillance for Clinical Stage I Testicular Cancer.

Science.gov (United States)

Nayan, Madhur; Jewett, Michael A S; Hosni, Ali; Anson-Cartwright, Lynn; Bedard, Philippe L; Moore, Malcolm; Hansen, Aaron R; Chung, Peter; Warde, Padraig; Sweet, Joan; O'Malley, Martin; Atenafu, Eshetu G; Hamilton, Robert J

2017-01-01

Patients on surveillance for clinical stage I (CSI) testicular cancer are counseled regarding their baseline risk of relapse. The conditional risk of relapse (cRR), which provides prognostic information on patients who have survived for a period of time without relapse, have not been determined for CSI testicular cancer. To determine cRR in CSI testicular cancer. We reviewed 1239 patients with CSI testicular cancer managed with surveillance at a tertiary academic centre between 1980 and 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: cRR estimates were calculated using the Kaplan-Meier method. We stratified patients according to validated risk factors for relapse. We used linear regression to determine cRR trends over time. At orchiectomy, the risk of relapse within 5 yr was 42.4%, 17.3%, 20.3%, and 12.2% among patients with high-risk nonseminomatous germ cell tumor (NSGCT), low-risk NSGCT, seminoma with tumor size ≥3cm, and seminoma with tumor size testicular cancer is very low. Consideration should be given to adapting surveillance protocols to individualized risk of relapse based on cRR as opposed to static protocols based on baseline factors. This strategy could reduce the intensity of follow-up for the majority of patients. Our study is the first to provide data on the future risk of relapse during surveillance for clinical stage I testicular cancer, given a patient has been without relapse for a specified period of time. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The globular cluster ω Centauri and its RR Lyrae variables

International Nuclear Information System (INIS)

Dickens, R.J.

1989-07-01

The significance of some of the unusual characteristics of the globular cluster ωCentauri in various fundamental problems is explored. Interest is centred on the properties of the cluster RR Lyraes, and what they can contribute to studies of early cluster chemical enrichment, stellar pulsation, the distance scale, stellar evolution, stellar ages and the Oosterhoff period-shift problem. This article, which is intended to highlight problems and progress rather than give a comprehensive review, includes new results based on photometry of the RR Lyraes, red giants, subgiants, horizontal-branch and main sequence stars in the cluster. (author)

Dietary Intake of Meat Cooking-Related Mutagens (HCAs) and Risk of Colorectal Adenoma and Cancer: A Systematic Review and Meta-Analysis.

Science.gov (United States)

Chiavarini, Manuela; Bertarelli, Gaia; Minelli, Liliana; Fabiani, Roberto

2017-05-18

Much evidence suggests that the positive association between meat intake and colorectal adenoma (CRA) and cancer (CRC) risk is mediated by mutagenic compounds generated during cooking at high temperature. A number of epidemiological studies have estimated the effect of meat-related mutagens intake on CRC/CRA risk with contradictory and sometimes inconsistent results. A literature search was carried out (PubMed, Web of Science and Scopus) to identify articles reporting the relationship between the intake of meat-related mutagens (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline: DiMeIQx, benzo(a) pyrene (B(a)P) and "meat derived mutagenic activity" (MDM)) and CRC/CRA risk. A random-effect model was used to calculate the risk association. Thirty-nine studies were included in the systematic review and meta-analysis. Polled CRA risk (15229 cases) was significantly increased by intake of PhIP (OR = 1.20; 95% CI: 1.13,1.28; p CRA risk in association with PhIP, MDM, and MeIQx. CRC risk (21,344 cases) was increased by uptake of MeIQx (OR = 1.14; 95% CI: 1.04,1.25; p = 0.004), DiMeIQx (OR = 1.12; 95% CI: 1.02,1.22; p = 0.014) and MDM (OR = 1.12; 95% CI: 1.06,1.19; p meat at high temperature may be responsible of its carcinogenicity.

Spectrophotometry of RR Telescopii

International Nuclear Information System (INIS)

Walker, A.R.

1977-01-01

The strongest emission lines in the nova-like variable RR Telescopii were measured during late 1974 using a spectrum scanner. The wavelength range 3350 to 7700 A was scanned with a resolution of 50 A. The results are compared with published spectrophotometry covering the period 1961 to 72, with the conclusion that few changes have taken place in the last 6 yr. No evidence was found that suggested the existence of a cool star, nor was there any indication of night-to-night changes in the emission line intensities. The spectrophotometry of the past 15 yr is consistent with an expanding shell, the emission from this shell being caused by high-energy radiation from an underlying star. (author)

Marketing a Healthy Mind, Body, and Soul: An Analysis of How African American Men View the Church as a Social Marketer and Health Promoter of Colorectal Cancer Risk and Prevention

Science.gov (United States)

Lumpkins, Crystal Y.; Vanchy, Priya; Baker, Tamara A.; Daley, Christine; Ndikum-Moffer, Florence; Greiner, K. Allen

2016-01-01

The Centers for Disease Control and Prevention ranks colorectal cancer (CRC) as the third most commonly diagnosed cancer among men in the United States; African American (AA) men are at even greater risk. The present study was from a larger study that investigates the church's role as a social marketer of CRC risk and prevention messages, and…

Divorce and risk of hospital-diagnosed infectious diseases.

Science.gov (United States)

Nielsen, Nete Munk; Davidsen, Rie B; Hviid, Anders; Wohlfahrt, Jan

2014-11-01

Although, divorce is considered to have a negative impact on morbidity, very little is known concerning exposure to divorce and risk of infectious diseases. We aimed to investigate the association between divorce and subsequent hospital contacts with infectious diseases. We performed a nation-wide cohort study, including all Danish men and women (n≈5.6 million) alive on the 1 January 1982 or later, and followed them for infectious disease diagnosed in hospital settings from 1982 to 2010. The association between divorce and risk of infectious diseases was evaluated through rate ratios (RRs) comparing incidence rates of infectious diseases between divorced and married pesons. Compared with married persons, divorced persons were overall at a 1.48 fold (RR=1.48 (95% CI: 1.47-1.50)) increased risk of hospital-diagnosed infectious diseases (RR adjusted for sex, age, period, income and education). The risk of infectious diseases was slightly more pronounced for divorced women (RR=1.54 (1.52-1.56)) than divorced men ((RR=1.42 (1.41-1.44)). The increased risk remained almost unchanged even more than 15 years after the divorce. Young age at divorce, short duration of marriage and number of divorces further increased the risk of infectious diseases, whereas number of children at time of divorce had no impact on risk of hospital-diagnosed infectious diseases following the divorce. Divorce appears to have a moderate but long lasting impact on the risk of infectious diseases the underlying mechanism is unknown but shared risk factors predicting divorce and infectious diseases could contribute to our findings. © 2014 the Nordic Societies of Public Health.

Menopausal hormone therapy and risk of melanoma: Do estrogens and progestins have a different role?

Science.gov (United States)

Botteri, Edoardo; Støer, Nathalie C; Sakshaug, Solveig; Graff-Iversen, Sidsel; Vangen, Siri; Hofvind, Solveig; Ursin, Giske; Weiderpass, Elisabete

2017-11-01

The association between use of menopausal hormone therapy (HT) and occurrence of skin malignant melanoma (SMM) is controversial. We investigated the issue in a nationwide cohort of 684,696 Norwegian women, aged 45-79 years, followed from 2004 to 2008. The study was based on linkage between Norwegian population registries. Multivariable Poisson regression models were used to estimate the effect of HT use, different HT types, routes of administration and doses of estrogen and progestin on the risk of SMM. During the median follow-up of 4.8 years, 178,307 (26%) women used HT, and 1,476 incident SMM cases were identified. Current use of HT was associated with increased risk of SMM (rate ratios (RR) = 1.19; 95% confidence interval (CI) 1.03-1.37). Plain estrogen therapy was associated with an increased risk of SMM (RR 1.45; 95% CI 1.21-1.73), both for oral (RR 1.45; 95% CI 1.09-1.93) and vaginal (RR 1.44; 95% CI 1.14-1.84) formulations, while combined estrogen and progestin therapy (EPT) was not (RR 0.91; 95% CI 0.70-1.19). We performed a dose-response analysis of estrogen and progestin in women using tablets, and found that use of estrogens was associated with increased risk (RR 1.24; 95% CI 1.00-1.53 per 1 mg/day) and use of progestins with decreased risk (RR 0.71; 95% CI 0.57-0.89 per 10 mg/month) of SMM. In conclusion, estrogens were associated with increased risk of SMM, while combinations of estrogens and progestins were not. Our results suggest that estrogens and progestins might affect the risk of SMM in opposite ways. © 2017 UICC.

Body mass index, physical activity, and risk of adult meningioma and glioma: A meta-analysis.

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Niedermaier, Tobias; Behrens, Gundula; Schmid, Daniela; Schlecht, Inga; Fischer, Beate; Leitzmann, Michael F

2015-10-13

Whether adiposity and lack of physical activity affect the risk for developing meningioma and glioma is poorly understood. Our objective was to characterize these associations in detail. We conducted a systematic review and meta-analysis of adiposity and physical activity in relation to meningioma and glioma using cohort and case-control studies published through February 2015. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified 12 eligible studies of body mass index (BMI) and 6 studies of physical activity, comprising up to 2,982 meningioma cases and 3,057 glioma cases. Using normal weight as the reference group, overweight (summary relative risk [RR] = 1.21, 95% confidence interval [CI] = 1.01-1.43) and obesity (RR = 1.54, 95% CI = 1.32-1.79) were associated with increased risk of meningioma. In contrast, overweight (RR = 1.06, 95% CI = 0.94-1.20) and obesity (RR = 1.11, 95% CI = 0.98-1.27) were unrelated to glioma. Similarly, dose-response meta-analyses revealed a statistically significant positive association of BMI with meningioma, but not glioma. High vs low physical activity levels showed a modest inverse relation to meningioma (RR = 0.73, 95% CI = 0.61-0.88) and a weak inverse association with glioma (RR = 0.86, 95% CI = 0.76-0.97). Relations persisted when the data were restricted to prospective studies, except for the association between physical activity and glioma, which was rendered statistically nonsignificant (RR = 0.91, 95% CI = 0.77-1.07). Adiposity is related to enhanced risk for meningioma but is unassociated with risk for glioma. Based on a limited body of evidence, physical activity is related to decreased risk of meningioma but shows little association with risk of glioma. © 2015 American Academy of Neurology.

Screening adherence and cancer risk perceptions in colorectal cancer survivors with Lynch-like syndrome.

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Katz, L H; Burton-Chase, A M; Advani, S; Fellman, B; Polivka, K M; Yuan, Y; Lynch, P M; Peterson, S K

2016-03-01

Cancer screening recommendations for patients with Lynch-like syndrome (LLS) are not well defined. We evaluated adherence to Lynch syndrome (LS) screening recommendations, cancer risk perceptions, and communication within the families among colorectal cancer (CRC) survivors with LLS. Thirty-four participants with LLS completed a questionnaire about risk perception, adherence to LS screening recommendations, and communication with relatives. Clinical data were obtained from medical records. Most participants (76%) believed they should undergo colonoscopy every 1-2 years. Only 41% correctly interpreted their genetic tests as uninformative negative or as variant of unknown significance for LS. Less than half had had an upper gastrointestinal endoscopy for screening purpose. Among female participants, 86% had been screened for endometrial cancer (EC) and 71% for ovarian cancer. Most participants had informed relatives about the CRC diagnosis and advised them to undergo CRC screening, but only 50% advised female relatives to be screened for EC and only one-third advised relatives to have genetic counseling. Most CRC survivors with LLS follow the same cancer screening recommended for LS patients but do not understand the meaning of LLS. Greater care must be devoted to communicating the implications of nondiagnostic germline mutation testing among patients with LLS. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Do HMO market level factors lead to racial/ethnic disparities in colorectal cancer screening? A comparison between high-risk Asian and Pacific Islander Americans and high-risk whites.

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Ponce, Ninez A; Huh, Soonim; Bastani, Roshan

2005-11-01

Few studies have explored health care market structure and colorectal cancer (CRC) screening test use, and little is known whether market factors contribute to racial/ethnic screening disparities. We investigated whether HMO market level factors, controlling for individual covariates, differentially impact Asian American and Pacific Islander (AAPI) subjects' access to CRC screening compared with white subjects. We used random intercept hierarchical models to predict CRC test use. Individual-level survey data was linked to market data by metropolitan statistical areas from InterStudy. Insured first-degree relatives, ages 40-80, of a random sample of colorectal cancer cases identified from the California Cancer Registry: 515 white subjects and 396 AAPI subjects residing in 36 metropolitan statistical areas (MSAs). Dependent variables were receipt of (1) annual fecal occult blood test only; (2) sigmoidoscopy in the past 5 years; (3) colonoscopy in the past 10 years; and (4) any of these tests over the recommended time interval. Market characteristics were HMO penetration, HMO competition, and proportion of staff/group/network HMOs. Market characteristics were as important as individual-level characteristics for AAPI but not for white subjects. Among AAPI subjects, a 10% increase in the percent of group/staff/network model HMO was associated with a reduction in colonoscopy use (28.9% to 20.5%) and in receipt of any of the CRC tests (53.2% to 45.4%). The prevailing organizational structure of a health care market confers a penalty on access to CRC test use among high-risk AAPI subjects but not among high-risk white subjects. Identifying the differential effect of market structure on race/ethnicity can potentially reduce the cancer burden among disadvantaged racial groups.

Vehicle rollover risk and electronic stability control systems.

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MacLennan, P A; Marshall, T; Griffin, R; Purcell, M; McGwin, G; Rue, L W

2008-06-01

Electronic stability control (ESC) systems were developed to reduce motor vehicle collisions (MVCs) caused by loss of control. Introduced in Europe in 1995 and in the USA in 1996, ESC is designed to improve vehicle lateral stability by electronically detecting and automatically assisting drivers in unfavorable situations. To examine the relationship between vehicle rollover risk and presence of ESC using a large national database of MVCs. A retrospective cohort study for the period 1995 through 2006 was carried out using data obtained from the National Automotive Sampling System General Estimates System. All passenger cars and sport utility vehicles (SUVs)/vans of model year 1996 and later were eligible. Vehicle ESC (unavailable, optional, standard) was determined on the basis of make, model, and model year. Risk ratios (RRs) and 95% CIs were calculated to compare rollover risk by vehicle ESC group. For all crashes, vehicles equipped with standard ESC had decreased risk of rollover (RR = 0.62, 95% CI 0.50 to 0.77) compared with vehicles with ESC unavailable. The association was consistent for single-vehicle MVCs (RR = 0.61, 95% CI 0.46 to 0.82); passenger cars had decreased rollover risk (RR = 0.77, 95% CI 0.52 to 1.12), but SUVs/vans had a more dramatically decreased risk (RR = 0.40, 95% CI 0.26 to 0.61). This study supports previous results showing ESC to be effective in reducing the risk of rollover. ESC is more effective in SUVs/vans for rollovers related to single-vehicle MVCs.

RR LYRAE ATMOSPHERICS: WRINKLES OLD AND NEW. A PREVIEW

International Nuclear Information System (INIS)

Preston, George W.

2011-01-01

I report some results of an echelle spectroscopic survey of RR Lyrae stars begun in 2006 that I presented in my Henry Norris Lecture of 2010 January 4. Topics include (1) atmospheric velocity gradients, (2) phase-dependent envelope turbulence as it relates to Peterson's discoveries of axial rotation on the horizontal branch and to Stothers' explanation of the Blazhko effect, (3) the three apparitions of hydrogen emission during a pulsation cycle, (4) the occurrence of He I lines in emission and absorption, (5) detection of He II emission and metallic line doubling in Blazhko stars, and finally (6) speculation about what helium observations of RR Lyrae stars in omega Centauri might tell us about the putative helium populations and the horizontal branch of that strange globular cluster.

Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations.

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Harsh Sheth

Full Text Available Regular aspirin use is associated with reduced risk of colorectal cancer (CRC. Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs. We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05. Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction (P = 0.001. Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only (P = 0.01 and P = 0.004, respectively, however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively; stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68-0.86; rs1105879 OR = 0.77 95% CI = 0.69-0.86 compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively, with the direction of association similar to

CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 1, 2, AND 3 OF CRYSTAL RIVER UNIT 3

International Nuclear Information System (INIS)

Wright, Kenneth D.

1997-01-01

The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 1, 2, and 3 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies

Family history and the risk of stomach cancer death in Japan: differences by age and gender.

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Yatsuya, Hiroshi; Toyoshima, Hideaki; Mizoue, Tetsuya; Kondo, Takaaki; Tamakoshi, Koji; Hori, Yoko; Tokui, Noritaka; Hoshiyama, Yoshiharu; Kikuchi, Shogo; Sakata, Kiyomi; Hayakawa, Norihiko; Tamakoshi, Akiko; Ohno, Yoshiyuki; Yoshimura, Takesumi

2002-02-10

Familial aggregation of stomach cancer has long been observed. The effect on disease risk of family history and its magnitude according to the type of affected relatives, however, is not well known. We conducted a prospective analysis using the JACC study (Japan Collaborative Cohort Study For Evaluation of Cancer Risk, sponsored by Monbusho) data. During the follow-up period, 662 stomach cancer deaths were documented. A positive history of stomach cancer in one or more first-degree relatives was associated with a significantly increased risk of death from the disease in both men (RR 1.60; 95% CI 1.11-2.31) and women (RR 2.47; 95% CI 1.50-4.06). In the subanalysis stratified by age, the association between positive family history and stomach cancer was stronger in the age group from 40-59 (RR 2.62; 95% CI 1.34-5.11 for men and RR 5.88; 95% CI 2.70-12.82 for women) than in the age group from 60-79 (RR 1.31; 95% CI 0.84-2.05 for men and RR 1.44; 95% CI 0.72-2.88 for women). In the age group from 40-59, men with father's history and women with mother's and sister's history of the disease had a significantly increased risk (RR 3.14; 95% CI 1.51-6.55, RR 10.46; 95% CI 4.54-24.12, RR 13.39; 95% CI 3.89-46.12, respectively). When 2 or more family members were affected, the increment in the risk was prominent especially in women (RR 9.45; 95% CI 4.46-20.05). These results suggest the existence of a certain subtype of stomach cancer that is inherited more often by women from one generation to the next in gender-influenced fashion. Any preventive strategy should take into account the degree of individual susceptibility. Copyright 2001 Wiley-Liss, Inc.

Risk factors for inappropriate blood requisition among hospitals in Tanzania.

Science.gov (United States)

Mauka, Wilhellmuss I; Mtuy, Tara B; Mahande, Michael J; Msuya, Sia E; Mboya, Innocent B; Juma, Abdul; Philemon, Rune N

2018-01-01

Blood is a critical aspect of treatment in life saving situations, increasing demand. Blood requisition practices greatly effect sufficient supply in blood banks. This study aimed to determine the risk factors for inappropriate blood requisition in Tanzania. This was a cross sectional study using secondary data of 14,460 patients' blood requests from 42 transfusion hospitals. Primary data were obtained by using cluster-sampling design. Data were analysed using a two-level mixed-effects Poisson regression to determine fixed-effects of individual-level factors and hospital level factors associated with inappropriate blood requests. P-value Factors significantly associated with inappropriate requisition were; reporting pulse rate and capillary refill decrease the risk (RR 0.74; 95% CI 0.64, 0.84) and (RR 0.73; 95% CI 0.63, 0.85) respectively and the following increased the risk; having surgery during hospital stay (RR 1.22; 95% CI 1.06, 1.4); being in general surgical ward (RR 3.3; 95% CI 2.7, 4.2), paediatric ward (RR 1.8; 95% CI 1.2, 2.7), obstetric ward (RR 2.5; 95% CI 2.0, 3.1), gynaecological ward (RR 2.1; 95% CI 1.5, 2.9), orthopaedics ward (RR 3.8; 95% CI 2.2, 6.7). Age of the patient, pallor and confirmation of pre-transfusion haemoglobin level were also significantly associated with inappropriate requisition. Majority of appropriate requisitions within the wards were marked in internal medicine (91.7%) and gynaecological wards (77.8%). The proportion of inappropriate blood requests was high. Blood requisition was determined by clinical and laboratory findings and the ward patients were admitted to. Adherence to transfusion guidelines is recommended to assure the best use of limited blood supply.

Nitrate in drinking water and colorectal cancer risk