BACKGROUND AND PURPOSE: CAS carries an inherent risk of distal cerebral embolization, precipitating new brain ischemic lesions and neurologic symptoms. Our purpose was to evaluate the frequency of new ischemic lesions found on DWI after protected CAS placement and to determine its association with plaque morphology.

Prevalence of multiple sclerosis varies with geographic latitude. We hypothesized that this fact might be partially associated with the influence of latitude on circadian rhythm and consequently that genetic variability of key circadian rhythm regulators, ARNTL and CLOCK genes, might contribute to the risk for multiple sclerosis. Our aim was to analyse selected polymorphisms of ARNTL and CLOCK, and their association with multiple sclerosis. A total of 900 Caucasian patients and 1024 healthy controls were compared for genetic signature at 8 SNPs, 4 for each of both genes. We found a statistically significant difference in genotype (ARNTL rs3789327, P = 7.5·10−5; CLOCK rs6811520 P = 0.02) distributions in patients and controls. The ARNTL rs3789327 CC genotype was associated with higher risk for multiple sclerosis at an OR of 1.67 (95% CI 1.35–2.07, P = 0.0001) and the CLOCK rs6811520 genotype CC at an OR of 1.40 (95% CI 1.13–1.73, P = 0.002). The results of this study suggest that genetic variability in the ARNTL and CLOCK genes might be associated with risk for multiple sclerosis.

Down syndrome (DS, also known as trisomy 21) most often results from chromosomal nondisjunction during oogenesis. Numerous studies sustain a causal link between global DNA hypomethylation and genetic instability. It has been suggested that DNA hypomethylation might affect the structure and dynamics of chromatin regions that are critical for chromosome stability and segregation, thus favouring chromosomal nondisjunction during meiosis. Maternal global DNA hypomethylation has not yet been analyzed as a potential risk factor for chromosome 21 nondisjunction. This study aimed to asses the risk for DS in association with maternal global DNA methylation and the impact of endogenous and exogenous factors that reportedly influence DNA methylation status. Global DNA methylation was analyzed in peripheral blood lymphocytes by quantifying LINE-1 methylation using the MethyLight method. Levels of global DNA methylation were significantly lower among mothers of children with maternally derived trisomy 21 than among control mothers (P = 0.000). The combination of MTHFR C677T genotype and diet significantly influenced global DNA methylation (R2 = 4.5%, P = 0.046). The lowest values of global DNA methylation were observed in mothers with MTHFR 677 CT+TT genotype and low dietary folate. Although our findings revealed an association between maternal global DNA hypomethylation and trisomy 21 of maternal origin, further progress and final conclusions regarding the role of global DNA methylation and the occurrence of trisomy 21 are facing major challenges.

Interactions of cell with the extracellular matrix (ECM) are crucial for normal development and functioning of the human organism. By regulating ECM integrity and composition matrix metalloproteinases (MMPs) play the main role in ECM molecules signaling and influence processes such as proliferation, migration, differentiation and apoptosis.ECM remodeling is a highly regulated process. When imbalanced it could contribute to pathophysiology of many diseases. The MMPs actions and activity are regulated through different mechanisms such as regulation of transcription, activation of latent MMPs, inhibition of MMP function by tissue inhibitors of metalloproteinases. MMPs are a family of calcium-and zinc-dependent endoproteinase, which share similar structural domains, but differs in substrate specificity, cell localizations and inducibility. Genetic variations in MMPs have been associated with a number of diseases, still not all findings are reproducible. Nine of 23 human genes encoding MMPs are located in a cluster on chromosome 11, which implicate their haplotype-driven effects. They could be important mediators of disease severity and could trigger acute events. In this chapter, we will review the basics of MMP biology and the most significant associations of MMPs variations with cardiovascular and neurological diseases in humans and MMPs therapeutic potential through synthetic inhibitors.

Toll-like receptors 2,4 and NFkB mediate inflammation in cholesteatoma and mucosal lesions oftubotympanic otitis in children and adults. Significant correlations betweenall pairs of molecules in all samples were detected in adults, but only TLR4-NFkappaB in children.