Effects of the Focused Ion Beam Parameters on Nanopore Milling in Solid State Membranes

AbstractThis work describes a reliable nanofabrication technology of solid state nanopore arrays. The geometric parameters of pores are achieved and optimized according to the requirements of bioanalytical applications regarding conformation and size of the characteristic proteins in clinical diagnostics. Different structural configurations and material compositions of the nanopore structures were developed and characterised according to the variable biofunctionalisation strategies. The geometry of the fabricated pores were analysed as the statistical function of the focused ion beam milling parameters

Differences in Beliefs About Cholesterol-Lowering Medications Among the Visegrad Group Countries: A Cross-Sectional Study

Background: New cholesterol guidelines highlight more personalized risk assessments and new cholesterol-lowering drugs for people at the highest risk for cardiovascular disease. Adherence due to fear of and lack of trust in medications prevents treatment to provide better health outcomes. / Objectives: The aim of our study was to investigate the possible differences in the beliefs about the necessity and concerns regarding lipid-lowering drugs among the Visegrad Group countries. / Methods: The Beliefs About Medicines Questionnaire (BMQ-Specific) was used in our research. The responses of 205 Hungarian, 200 Slovak, 235 Czech, and 200 Polish participants, all taking cholesterol-lowering medications, were compared to each other. / Results: Hungarian participants' belief in the necessity of cholesterol-lowering drugs was significantly lower compared to the Slovak (P = 0.001), Czech (P = 0.037), and Polish (P < 0.001) participants. While no difference was observed between the Czech and Slovak responses (P = 0.154), both the Czech (P < 0.001) and Slovak (P = 0.006) respondents' belief regarding necessity was lower than that of the Polish. Regarding concerns, the only significant difference was observed between the Czech and the Polish respondents (P = 0.011). / Conclusions: While the beliefs about benefits (necessity) are most prominent among the Polish participants, except in comparison to Czech responses, the Visegrad Group countries do not differ considerably regarding their beliefs about the fear (concerns) of the treatment

Prevalent Polymorphism in Thyroid Hormone-Activating Enzyme Leaves a Genetic Fingerprint that Underlies Associated Clinical Syndromes

Context: A common polymorphism in the gene encoding the activating deiodinase (Thr92Ala-D2) is known to be associated with quality of life in millions of patients with hypothyroidism and with several organ-specific conditions. This polymorphism results in a single amino acid change within the D2 molecule where its susceptibility to ubiquitination and proteasomal degradation is regulated. Objective: To define the molecular mechanisms underlying associated conditions in carriers of the Thr92Ala-D2 polymorphism. Design, Setting, Patients: Microarray analyses of nineteen postmortem human cerebral cortex samples were performed to establish a foundation for molecular studies via a cell model of HEK-293 cells stably expressing Thr92 or Ala92 D2. Results: The cerebral cortex of Thr92Ala-D2 carriers exhibits a transcriptional fingerprint that includes sets of genes involved in CNS diseases, ubiquitin, mitochondrial dysfunction (chromosomal genes encoding mitochondrial proteins), inflammation, apoptosis, DNA repair and growth factor signaling. Similar findings were made in Ala92-D2-expressing HEK-293 cells and in both cases there was no evidence that thyroid hormone signaling was affected, i.e. the expression level of T3-responsive genes was unchanged, but that several other genes were differentially regulated. The combined microarray analyses (brain/cells) led to the development of an 81-gene classifier that correctly predicts the genotype of homozygous brain samples. In contrast to Thr92-D2, Ala92-D2 exhibits longer half-life and was consistently found in the Golgi. A number of Golgi-related genes were down-regulated in Ala92-D2-expressing cells but were normalized after 24h-treatment with the antioxidant N-acetylecysteine. Conclusions: Ala92-D2 accumulates in the Golgi, where its presence and/or ensuing oxidative stress disrupts basic cellular functions and increases pre-apoptosis. These findings are reminiscent to disease mechanisms observed in other neurodegenerative disorders such as Huntington's disease, and could contribute to the unresolved neurocognitive symptoms of affected carriers

Hyperhomocysteinaemia and MTHFR C677T gene polymorphism in renal transplant recipients

Aim-To study the effect of folate treatment on hyperhomocysteinaemia and the effect of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism on total homocysteine and folate concentrations after renal transplantation. Methods-A total of 30 transplanted children and adolescents were investigated for total homocysteine and folate serum concentrations before and after folate treatment, as well as for the presence of the MTHFR C677T polymorphism. Results-The allele frequency of C677T polymorphism in the MTHFR gene in the study population (0.33) was not different to that in controls (0.38). Before folate treatment the homocysteine concentration was raised in all groups; following folate supplementation it was significantly decreased in the CC and CT groups, but not in the TT group. In patients with CC genotype, serum homocysteine correlated with serum creatinine and cholesterol, and time since transplantation before treatment. Conclusion-Folate supplementation appears to be an effective strategy to normalise total homocysteine concentration in renal transplanted children and adolescents