Research of Russian physicians' opinions on tuberculosis pharmacogenetics.

BACKGROUND: There is currently no widespread implementation of pharmacogenetic testing (PGx) methods in the practice of phthisiology service. OBJECTIVE: The aim of this study is to determine how informed and prepared phthisiologists, residents, and postgraduate students of the Russian Medical Academy of Continuing Professional Education (RMACPE, Moscow) use PGx techniques in their work to improve treatment safety, predict the occurrence of adverse reactions (ADRs), and personalize therapy. METHODS: A survey was conducted among phthisiologists (n = 314) living in different regions of the Russian Federation and studying at RMACPE, such as residents and post-graduate students (n = 185). The survey was developed on the Testograf.ru web platform and had 25 questions for physicians and 22 for residents and post-graduate students. RESULTS: More than 50% of respondents are ready to use PGx in clinical practice and thus are aware of the method's possibilities. At the same time only a small part of participants were aware of the pharmgkb.org resource. The absence of PGx in clinical guidelines and treatment standards, according to 50.95% of phthisiologists and 55.13% of students of RMACPE, the absence of large-scale randomized clinical trials, according to 37.26% of phthisiologists and 43.33% of students, and the lack of physician knowledge on PGx, according to 41.08% of phthisiologists and 57.83% of students, are all factors that prevent the implementation of PGx in Russia. CONCLUSION: According to the survey, the overwhelming majority of participants recognize the importance of PGx and are willing to use the method in practice. However, there is a low level of awareness among all respondents about the possibilities of PGx and the pharmgkb.org resource. The implementation of this service could significantly increase patient compliance, lower ADRs, and enhance anti-tuberculosis (TB) therapy quality.

[Modeling of mechanochemical DNA cleavage by action of ultrasound].

This study offers a simulation of the stretching dynamics of a double-stranded DNA fragment in the high-gradient flow of fluid near collapsing cavitation bubbles. Calculated profiles of elastic tension along the model of a polymer fragment were used to estimate the rates of mechanochemical cleavage at different positions of DNA restriction fragments. The resulting cleavage rate profiles are qualitatively consistent with the experimentally observed profiles of ultrasonic cleavage rates of DNA restriction fragments, which are position-dependent. The proposed model also relates the sequence specificity of ultrasonic DNA cleavage, which was experimentally detected earlier, to the peculiarities of sequence-specific conformational dynamics of ß-D-deoxyribose in the B-form double helix. A quantitative assessment of the ultrasonic DNA cleavage rates for different conformational states of ß-D-deoxyribose derived from the proposed model qualitatively agrees with the experimental data.

Unsupervised learning in detection of gene transfer.

The tree representation as a model for organismal evolution has been in use since before Darwin. However, with the recent unprecedented access to biomolecular data, it has been discovered that, especially in the microbial world, individual genes making up the genome of an organism give rise to different and sometimes conflicting evolutionary tree topologies. This discovery calls into question the notion of a single evolutionary tree for an organism and gives rise to the notion of an evolutionary consensus tree based on the evolutionary patterns of the majority of genes in a genome embedded in a network of gene histories. Here, we discuss an approach to the analysis of genomic data of multiple genomes using bipartition spectral analysis and unsupervised learning. An interesting observation is that genes within genomes that have evolutionary tree topologies, which are in substantial conflict with the evolutionary consensus tree of an organism, point to possible horizontal gene transfer events which often delineate significant evolutionary events.

[Tunneling of autowaves through unexcitable parts of active media]. / Tunnelirovanie avtovoln cherez nevozbudimye uchastki aktivnykh sred.

The mechanisms of propagation of autowaves through local heterogeneities in active media were studied by computer simulation. The model proposed by Zel'dovich and Frank-Kamenetsky and that of FitzHugh-Nagumo were used for studying autowave tunneling. It was shown that the underbarrier passage of an autowave through a nonexcitable area is limited by threshold values. It was shown that, for every fixed parameter value corresponding to the degree of nonexcitability of a local area, there exists a critical value for nonexcitable zone latitude. An autowave overcomes the barrier and continues to propagate when the value of zone latitude is less than the critical. Critical conditions for the origination of sources of secondary periodical sequences of impulses in excitable medium were found. It was shown that the properties of sources of secondary autowaves can be modified by regulating the size of the nonexcitable zone and the zone of increased excitability. In particular, the conditions were explored under which spatial irregularity behaves as a source of a unidirectional and/or an asynchronous sequence of impulses.

Autowave tunneling through a non-excitable area of active media.

The mechanisms of autowaves propagation through local non-homogeneities in active media relevant to diverse class of physiological systems were studied by means of a computer simulation. The model proposed by Zel'dovich and Frank-Kamenetsky and that of FitzHugh-Nagumo were used for studying autowave tunneling, which in a broad sense implies underbarrier passing. It was shown that for every fixed parameter value corresponding to the degree of non-excitability of local area a critical value for non-excitable zone latitude exists. An autowave overcomes the barrier and continues to propagate when the value of zone latitude is less than critical. Critical conditions for origination of a source of periodical sequence of impulses in excitable medium were found. The source properties, as shown, can be modified by regulation of size of a non-excitable zone and a zone of higher excitability. In particular, the conditions when spatial irregularity behaves as a source of unidirectional and/or asynchronous sequence of impulses were explored.