Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients

BACKGROUND: Mismatch repair (MMR) genes are known to be frequently altered in colorectal cancer (CRC). Both genetics and epigenetics modifications seems to be relevant in this phenomenon, however it is still not clear how these two aspects are interconnected. The present study aimed at characterizing of epigenetic and gene expression profiles of MMR genes in sporadic CRC patients from the Czech Republic, a country with one of the highest incidences of this cancer all over Europe. METHODS: Expression levels and CpG promoter methylation status of all MMR genes were evaluated in DNA from tumor and adjacent mucosal samples of 53 incident CRC patients. RESULTS: We have found significantly increased transcription levels in EXO1 gene in tumor tissues (P = 0.05) and significant over-expression of MSH3 gene in colon tumors when compared to adjacent mucosal tissues (P = 0.02). Interestingly, almost all MMR genes were differently expressed when localization of tumors was compared. In particular, colon tumors showed an up-regulation of EXO1, MSH2, MSH3, MSH6, and PMS2 genes in comparison to rectal tumors (P = 0.02). Expression levels of all MMR genes positively correlated between each other. The promoter methylation of MLH1 gene was observed in 9% of CRC tissues only. CONCLUSIONS: In our study, we have observed different pattern of MMR genes expression according to tumor localization. However, a lack of association between methylation in MMR genes and their corresponding expressions was noticed in this study, the relationship between these two aspects is worthy to be analyzed in larger population studies and in pre-malignant stages

Multi-Contextual Smart City Model for Service Interconnections

The keyissueofsmartcitydevelopmentusuallyliesintheunder- standing ofthecomplexityoftheservices’structure.Thus,smartcitymodels are developedtoimprovecurrentoutlooksonSmartCityServices’structure by usingservice-dominantlogicandservicescience.However,thecontextual changes areusuallynotfullyconsideredintheexistingsmartcitymodels.Itis in turndifficult tocatchthechangesamongthelayersinthesmartcitymodel. Therefore, inthispaper,weproposeacomplexandinnovativestructureofsmart city services.Themaincontributionoftheproposedapproachistoconsolidate the interconnectionofservicesthatisaffected bythechangingcontext.Itwill also leadtoabetterunderstandingofthecomplexityinasmartcity.Thepre- sented conceptualmodelhasadirectinfluenceonthepracticaldevelopment of asmartcity.Sinceeverycountryandcityapproachestheservices’struc- ture differently,thesmartcitymodelisderivedwiththelackofacommon understanding ofvarioussmartcities.Inthecaseofacceptingourmodelasa common solution,thesharingofknowledgeandinformationamongcitiesand countries wouldbeeasierandmorevaluable.Thepaperalsoshowshowthecur- rent knowledgeinservice-dominantlogicandservicesciencehelpstodevelop a newpracticalapproachtounderstandingthesmartcitystructure

The impact of limited language proficiency in screening for breast cancer

Background: The prevalence of a culturally diverse population in the United States continues to grow. Nevertheless, the national impact of limited English proficiency (LEP) in breast cancer screening is still unknown. Methods: A retrospective review of the 2015 sample of the National Health Interview Survey database was performed. The cohort included women with and without LEP between 40 and 75 years. We evaluated differences in screening rates, baseline, socioeconomic, access to healthcare, and breast cancer risk factors with univariate and multivariate regression analyses. Results: The prevalence of LEP was 5.7% (N = 1825, weighted counts 3936,081). LEP women showed a statistically significant lower rate of overall screening mammograms (78% vs. 90%), fewer benign lumps removed (6.4% vs. 17%) and lower rates of access to healthcare variables. They showed a higher rate of nonprivate insurance and living below the poverty line, a lower rate of hormone replacement therapy (1.8% vs. 5.6%), older menarche (12.97 vs. 12.75) and a higher rate of current menstruation (36% vs. 24). LEP women were associated with a lower probability of having a screening mammogram in multivariate analysis (OR: 0.67, 95% CI: 0.51-0.87). When LEP was subdivided into Spanish and other languages, Spanish speakers were associated with a lower probability of a screening mammogram (OR 0.67, 95% CI 0.49-0.90) while controlling for the same covariates. Conclusion: The results from our study showed that LEP women are associated with a lower probability of having a screening mammogram. Particularly, the Spanish speakers were found as a vulnerable subgroup

Dietary fat and physiological determinants of plasma chylomicron remnant homoeostasis in normolipidaemic subjects: insight into atherogenic risk.

TAG depleted remnants of postprandial chylomicrons are a risk factor for atherosclerosis. Recent studies have demonstrated that in the fasted state, the majority of chylomicrons are small enough for transcytosis to arterial subendothelial space and accelerate atherogenesis. However, the size distribution of chylomicrons in the absorptive state is unclear. This study explored in normolipidaemic subjects the postprandial distribution of the chylomicron marker, apoB-48, in a TAG-rich lipoprotein plasma fraction (Svedberg flotation rate (Sf>400), in partially hydrolysed remnants (Sf 20-400) and in a TAG-deplete fraction (Sf<20), following ingestion of isoenergetic meals with either palm oil (PO), rice bran or coconut oil. Results from this study show that the majority of fasting chylomicrons are within the potentially pro-atherogenic Sf<20 fraction (70-75 %). Following the ingestion of test meals, chylomicronaemia was also principally distributed within the Sf<20 fraction. However, approximately 40 % of subjects demonstrated exaggerated postprandial lipaemia specifically in response to the SFA-rich PO meal, with a transient shift to more buoyant chylomicron fractions. The latter demonstrates that heterogeneity in the magnitude and duration of hyper-remnantaemia is dependent on both the nature of the meal fatty acids ingested and possible metabolic determinants that influence chylomicron metabolism. The study findings reiterate that fasting plasma TAG is a poor indicator of atherogenic chylomicron remnant homoeostasis and emphasises the merits of considering specifically, chylomicron remnant abundance and kinetics in the context of atherogenic risk. Few studies address the latter, despite the majority of life being spent in the postprandial and absorptive state