Can Croatia Join Europe as Competitive Knowledge-based Society by 2010?

The 21st century has brought important changes in the paradigms of economic development, one of them being a shift toward recognizing knowledge and information as the most important factors of today. The European Union (EU) has been working hard to become the most competitive knowledge-based society in the world, and Croatia, an EU candidate country, has been faced with a similar task. To establish itself as one of the best knowledge-based country in the Eastern European region over the next four years, Croatia realized it has to create an education and science system correspondent with European standards and sensitive to labor market needs. For that purpose, the Croatian Ministry of Science, Education, and Sports (MSES) has created and started implementing a complex strategy, consisting of the following key components: the reform of education system in accordance with the Bologna Declaration; stimulation of scientific production by supporting national and international research projects; reversing the “brain drain” into “brain gain” and strengthening the links between science and technology; and informatization of the whole education and science system. In this comprehensive report, we describe the implementation of these measures, whose coordination with the EU goals presents a challenge, as well as an opportunity for Croatia to become a knowledge-based society by 2010.     

Correlation and regression

Correlation and regression are statistical methods that help us determine interactions of variables. Both are being used in statistical analysis of basic and clinical research. Correlation (r) is a measure of linear relationship between two numerical measurements made on the same set of subjects and it is represented by correlation coefficient. Values of correlation coefficient range between -1 and 1. Pearson's and Spearman's coefficients of correlation are the most often used correlation coefficients. Correlation can be linear and non-linear. We calculate the significance of correlation (P) in an effort to determine significance of correlation coefficient. Regression is a statistical method that allows us to predict values of one variable from another. The simplest regression is linear regression. The success of regression equation is valued by analysis of residuals. Multiple regression is used to predict one variable from several known variables.     

Attenuated virulence of a Burkholderia cepacia type III secretion mutant in a murine model of infection

Type III secretion systems are utilized by a number of gram-negative bacterial pathogens to deliver virulence-associated proteins into host cells. Using a PCR-based approach, we identified homologs of type III secretion genes in the gram-negative bacterium Burkholderia cepacia, an important pulmonary pathogen in immunocompromised patients and patients with cystic fibrosis. One of the genes, designated bscN, encodes a member of a family of ATP-binding proteins believed to generate energy driving virulence protein secretion. Genetic dissection of the regions flanking the bscN gene revealed a locus consisting of at least 10 open reading frames, predicted to encode products with significant homology to known type III secretion proteins in other bacteria. A defined null mutation was generated in the bscN gene, and the null strain and wild-type parent strain were examined by use of a murine model of B. cepacia infection. Quantitative bacteriological analysis of the lungs and spleens of infected C57BL/6 mice revealed that the bscN null strain was attenuated in virulence compared to the parent strain, with significantly lower bacterial recovery from the lungs and spleens at 3 days postinfection. Moreover, histopathological changes, including an inflammatory cell infiltrate, were more pronounced in the lungs of mice infected with the wild-type parent strain than in those of mice infected with the isogenic bscN mutant. These results implicate type III secretion as an important determinant in the pathogenesis of B. cepacia.     

Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment

Variation in the human genome is a most important cause of variable response to drugs and other xenobiotics. Susceptibility to almost all diseases is determined to some extent by genetic variation. Driven by the advances in molecular biology, pharmacogenetics has evolved within the past 40 years from a niche discipline to a major driving force of clinical pharmacology, and it is currently one of the most actively pursued disciplines in applied biomedical research in general. Nowadays we can assess more than 1,000,000 polymorphisms or the expression of more than 25,000 genes in each participant of a clinical study -- at affordable costs. This has not yet significantly changed common therapeutic practices, but a number of physicians are starting to consider polymorphisms, such as those in CYP2C9, CYP2C19, CYP2D6, TPMT and VKORC1, in daily medical practice. More obviously, pharmacogenetics has changed the practices and requirements in preclinical and clinical drug research; large clinical trials without a pharmacogenomic add-on appear to have become the minority. This review is about how the discipline of pharmacogenetics has evolved from the analysis of single proteins to current approaches involving the broad analyses of the entire genome and of all mRNA species or all metabolites and other approaches aimed at trying to understand the entire biological system. Pharmacogenetics and genomics are becoming substantially integrated fields of the profession of clinical pharmacology, and education in the relevant methods, knowledge and concepts form an indispensable part of the clinical pharmacology curriculum and the professional life of pharmacologists from early drug discovery to pharmacovigilance.     

The Role of Haematological Parameters in Predicting the Response To Radical Chemoradiotherapy in Patients with Anal Squamous Cell Cancer

BackgroundHistorically, the treatment of choice for anal cancer had been abdominoperineal resection (APR). Radical radiotherapy with concurrent 5-fluorouracil plus mitomycin C chemotherapy was later established as standard therapy, although with a failure rate of 20–30%. The aim of this study was to evaluate the outcomes after radical chemoradiotherapy (CRT), prognostic and predictive factors and patterns of failure.Patients and methodsThis study included 47 patients treated with radical CRT for patohistologicaly confirmed anal squamous cell carcinoma. Analysed haematological parameters included: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and haemoglobin level. The final logistic regression model included treatment break period. Tumour response was assessed at 24 weeks from CRT completion. Follow-up was performed every 3 months during the first two years, and every 6 months thereafter.ResultsA complete clinical response (CR) was detected in 30 patients (63.8%). Patients who did not achieve a 6-months CR and those who had a CR after 6 months but then relapsed were referred to surgical treatment. With combined CRT and surgical salvage treatment the CR rate was 80.9%. Patients with CR after 6 months had significantly longer disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS). A significant effect on the 6-month response was confirmed for PLR (p = 0.03).ConclusionsImportant prognostic factors associated with CR were baseline haemoglobin level and period of treatment interruptions. Potential haematological prognostic factors could be PLR and NLR, which can be routinely determined by low-cost and minimally invasive methods.Key words: anal cancer, chemoradiotherapy, haematological parameters