Exploring pharmacogenetic variation in a Bulgarian psychiatric cohort

Introduction: Pharmacogenetics in psychiatry is currently gaining momentum. The efficiency of antipsychotic therapy is often limited by the lack of response and the presence of side effects. Pharmacogenetic variation is probably one of the causative factors for the observed interindividual differences in the response to and the side effects of antipsychotics, which could be addressed and whose negative effects could be avoided or mitigated.Aim: The present study aimed to conduct a comprehensive analysis of the frequency of DRD2 rs1799732, COMT rs4680, MC4R rs489693, and HTR2C rs3813929 in Bulgarian psychiatric patients.Materials and methods: The frequency of genotypes and the alleles of variants DRD2 rs1799732, COMT rs4680, MC4R rs489693, and HTR2C rs3813929 were studied in a cohort of 515 Bulgarian psychiatric patients using the polymerase chain reaction (PCR) method.Results: We found no significant difference between our cohort and the dataset of the 1000 Genomes Project. Moreover, we found that 433 out of 515 patients carried at least one, and 191 out of 515 carried at least two variants which, based on multiple scientific sources with consistent findings, could potentially alter the expected response rate, time to respond and/or risk of side effects to antipsychotic medications.Conclusions: Considering the consistent data about the frequency of these pharmacogenetic variants, testing these genetic variants may prove useful in clinical practice. Further studies regarding the clinical interpretation and frequency distribution in larger cohorts and different populations are warranted

Exploring pharmacogenetic variation in a Bulgarian psychiatric cohort

Introduction: Pharmacogenetics in psychiatry is currently gaining momentum. The efficiency of antipsychotic therapy is often limited by the lack of response and the presence of side effects. Pharmacogenetic variation is probably one of the causative factors for the observed interindividual differences in the response to and the side effects of antipsychotics, which could be addressed and whose negative effects could be avoided or mitigated.Aim: The present study aimed to conduct a comprehensive analysis of the frequency of DRD2 rs1799732, COMT rs4680, MC4R rs489693, and HTR2C rs3813929 in Bulgarian psychiatric patients.Materials and methods: The frequency of genotypes and the alleles of variants DRD2 rs1799732, COMT rs4680, MC4R rs489693, and HTR2C rs3813929 were studied in a cohort of 515 Bulgarian psychiatric patients using the polymerase chain reaction (PCR) method.Results: We found no significant difference between our cohort and the dataset of the 1000 Genomes Project. Moreover, we found that 433 out of 515 patients carried at least one, and 191 out of 515 carried at least two variants which, based on multiple scientific sources with consistent findings, could potentially alter the expected response rate, time to respond and/or risk of side effects to antipsychotic medications.Conclusions: Considering the consistent data about the frequency of these pharmacogenetic variants, testing these genetic variants may prove useful in clinical practice. Further studies regarding the clinical interpretation and frequency distribution in larger cohorts and different populations are warranted

CYP2C19 and CYP2D6 Genotypes and Metabolizer Status Distribution in a Bulgarian Psychiatric Cohort

CYP2D6 and CYP2C19 are enzymes of essential significance for the pharmacokinetics of a multitude of commonly used antidepressants, antipsychotics, antiemetics, β-blockers, opioids, antiestrogen, antacids, etc. Polymorphisms in the respective genes are well established as resulting in functional differences, which in turn can impact safety and efficacy. Importantly, the prevalence of genetic CYP2D6 and CYP2C19 variability differs drastically between populations. Drawing on the limited information concerning genotype frequencies in Bulgaria, we here analyzed 742 Bulgarian psychiatric patients predominantly diagnosed with depression and/or anxiety. Specifically, we analyzed frequencies of CYPC19*2, *4 and *17, as well as of CYP2D6*2, *3, *4, *5, *6, *10 and *41. In total, 571 out of 742 patients (77%) carried at least one variant which impacts metabolizer status. Overall, 48.6% of the studied individuals were classified as non-normal metabolizers of CYP2D6 with most exhibiting reduced function (38.2% intermediate metabolizers and 6.6% poor metabolizers). In contrast, for CYP2C19, the majority of non-normal metabolizers showed increased functionality (28.9% rapid and 5.5% ultrarapid metabolizers), while reduced activity metabolizer status accounted for 25.6% (23.8% intermediate and 1.8% poor metabolizers). These results provide an important resource to assess the genetically encoded functional variability of CYP2D6 and CYP2C19 which may have significant implications for precision medicine in Bulgarian psychiatry practice

Synchrotron X-ray distinction of seasonal hydrological and temperature patterns in speleothem carbonate

Synchrotron micro-X-ray fluorescence (µXRF) spectrometry is used to reveal trace element patterns within speleothem calcite at the sub-annual scale and provide one of the first calibrations to prevailing meteorological conditions. Mapping of Zn and SO42– within speleothem calcite was performed at the European Synchrotron Radiation Facility over three annual cycles (1977–1979). Peaks in µXRF Zn concentrations occur on an annual basis, although banding of lower XRF intensity reveals multiple events at the sub-annual scale. The delivery of Zn to the speleothem was found to be dependent upon the presence of a water excess, the condition of any overlying snowpack and the pH of the soil solution as controlled by microbial activity. This generated a pattern of Zn event laminae that documented increasing concentrations from winter through to the following autumn and complies with existing models inferring surface-active trace metals are delivered to the point of speleothem growth in association with natural organic matter (referred to as NOM–metal complexes). Minimum and maximum concentrations of speleothem SO42– coincide with winter and summer respectively, in contrast to the near constant SO42– concentrations of the drip water. Fluctuations in speleothem SO42– levels closely follow changes in cave external temperatures, thereby validating existing models of sulfate incorporation into carbonate minerals thought to be driven by cave ventilation dynamics and internal cave atmospheric pCO2 (partial pressure). At the current resolution of analysis, this represents some of the first evidence linking event-based meteorological (temperature and precipitation) records to the trace element content of speleothem calcite, building towards reconstruction of indices of climatic change beyond the instrumental period

Immoral contracts in Europe

Tekstas VDU autorių 31 p. : p. 88-92, 155-157, 197-198, 246-248, 308-309, 369-370, 431-434, 482-484, 533-534, 574-575, 622-624, 686-688This book adds an in-depth study of the law and practice on immorality of contracts in Europe to the Common Core series. It comprises country reports on 28 European legal systems, in line with the editors ’ aspiration to give a comprehensive overview of shared and diverging views on immorality of contracts in the European Union. The reports have been draft ed on the basis of 12 case scenarios, inspired by real-life cases that were adjudicated in European countries. Furthermore, given the importance of societal debate for the assessment of morality in contract law, signifi cant attention is paid to the context in which the law on specifi c cases has developed. Th e combined insights from the national reports provide an overview of the current state of a “ Common Core ” on immoral contracts in Europe. Comparative legal studies performed by a large network of academics from many different countries usually require many years of work and, indeed, a great deal of patience from all persons involved. This book, like most volumes in the Common Core series, is no exception to this rule. We presented a first draft questionnaire on immoral contracts – or, more precisely, on the limits to the validity of contracts on ground of morality or public policy – at the General Meeting of the Common Core project in 2012. After settling on the fi nal version of the questionnaire, the first draft country reports were written between 2013–2015. The comparative remarks, the introductory chapters and the second and third draft s of the country reports were completed between 2016–2018. This past year was devoted to the final editing, updating and proofreading of the book. [...]Privatinės teisės katedraTeisės fakultetasVytauto Didžiojo universiteta