[Physical training in patients with chronic heart failure: level of involvement, as well as psychosocial, anamnestic and iatrogenic factors that determine the motivation to practice].

Introduction Physical exercise (PE) is a necessary part in the treatment of patients with chronic heart failure (CHF), which is stated in the European Society of Cardiology guidelines and the Russian Heart Failure Society guidelines. However, this type of non-drug treatment is still not sufficiently used in HF patients in Russia.Aim To study the current involvement of HF patients in PT and to describe psychosocial factors that influence the patients' willingness to exercise and potential barriers and motivations for PE.Methods This study was designed as an in-moment survey. Patients with CHF who visited clinics in 7 cities of the Russian Federation in 2018 as a part of European Heart Failure Awareness Days were provided with a self-administered questionnaire containing questions about their social and educational status, attitude to PT as a method of treatment, and factors motivating and demotivating them to participation in training sessions. The survey participants were also asked a question about their source of information about exercise in HF. Physicians filled in the items describing HF clinical manifestations (left ventricular ejection fraction (EF) and HF functional class (FC)). Code numbers were used for further identification of the participants and to protect their confidentiality. Statistical analysis was performed with the StatXcat-8 program. Limits of exact confidence intervals (CIs) were provided both for fractions and parameters of polynomial distribution. CI limits for differences and fractions were calculated using MOVER. Age was analyzed using the PAST program.Results The study included 560 patients with HF; 52 % of them were women (mean age, 64; 95 % CI: 63-65 years). Women were 3 years older than men (95 % CI: 1.3-4.9 years). 501 (89.5 %) patients had FC II-III; 265 (49 %) patients had HF with low EF. 350 (62 %) patients had comorbidities: 41.4 % of patients had diabetes mellitus and 25.4 % of patients had arthritis. Only 91 (17 %) patients reported exercising. Patients younger than 65 exercised significantly more frequently than older ones (odds ratio (OR), 1.7, 95 % CI: 1.0-2.7, р<0.001). Patients with higher education had better chances to be involved in PT or were more anxious to start training (OR, 2.7; 95 % CI: 1.6-4.7, р<0.001). The capability for influencing the disease was the major motivation for PT for both sexes. Probability of this answer was 48 % (95 % CI: 33-61) for men and 46 % (95 % CI: 29-63) for women. 62 % of patients indicated poor health as the major barrier for participation in PT. Only 55 % of patients knew that PT could be a method for HF treatment, and only 50 % were informed about that by their physician.Conclusion The factors that positively influence the willingness to exercise include male sex, higher level of education, younger age, and better perception of the own health condition. 62 % of patients indicated poor health as the major barrier for participation in training. On the whole, the awareness of patients about PT benefits for health in HF was low. To our opinion, this was a serious factor of the extremely low involvement of patients in PT. Only 55 % of patients knew that PT could be a method for HF treatment, and, furthermore, only 50 % of patients received this information from their physicians.

[Correct statistical analysis of genotype frequencies for UCP and PPAR gene families in residents of besieged Leningrad and the control group].

Correct harmonized statistical re-analysis of the data published in this Journal by I.V.Polyakova et al. (2014) clearly shows that, contrary to the authors' opinion, the distribution of genotypes among residents of besieged Leningrad and the residents of the North-West region of Russia appeared to be statistically indistinguishable in all five genes studied. The main causes of the erroneous conclusions of the authors are neglecting the problem of multiple comparisons and fundamental impossibility of sampling adequate control group. A scheme for harmonized statistical analysis of such data is presented. It implies not only frequentist but Bayesian point and interval estimates for genotype proportions and their differences, for fixation index (coefficient of inbreeding) FIS, for the effect size φ based on χ2 statistic (contingency coefficient) and for the achieved power (1 - ß), as well as estimates of posterior probabilities for the null hypothesis P(H_0 |D), Bayes factors 〖BF〗_01, observed p-values, p_obs, with the prediction intervals, and p-values adjusted for the multiplicity of null hypotheses tested (P_S).

[Genetic risk assessment of the joint effect of several genes: Critical appraisal].

When assessing the combined action of genes on the quantitative or qualitative phenotype we encounter a phenomenon that could be named the "paradox of the risk score summation." It arises when the search of risk allele and assessment of their combined action are performed with the same single dataset. Too often such methodological error occurs when calculating the so called genetic risk score (GRS), which refers to the total number of alleles associated with the disease. Examples from numerous published genetic association studies are considered in which the claimed statistically significant effects can be attributed to the "risk score summation paradox." In the second section of the review we discuss the current modifications of multiple regression analysis addressed to the so called "n ≪ p problem" (the number of points is much smaller than the number of possible predictors). Various algorithms for the model selection (searching the significant predictor combinations) are considered, beginning from the common marginal screening of the "top" predictors to LASSO and other modern algorithms of compressed sensing.

Comparative phenotypic characterization of human cord blood monocytes and placental macrophages at term.

The expression of surface molecules in cord blood monocytes and placental macrophages was studied using flow cytometry. When compared with monocytes, macrophages presented a decrease in HLA-DR and LAP/TGF-ß1 levels and increased expression of alternative activation markers, especially CD206. No difference in the production of the apoptotic factors TRAIL and TWEAK was observed, whereas the levels of cytokine receptors in monocytes were significantly higher than in macrophages. Most remarkable was the difference in the expression of IL-17 and TNFα receptors. A strong correlation between VEGF and TNFα receptors was revealed in both cell populations. The results obtained in this study provide antigenic phenotypes for two related cell populations and outline the feasible functional alterations during tissue macrophage differentiation.

[Enterovirus infection as a risk factor of acute coronary syndrome and its complications].

Antigens of enteroviruses were detected quantitatively in the modified complement-binding reaction in blood samples from 102 of the 208 (49%) patients with ACS, in coronary artery tissues from 23 of 24 and heart from 51 of 94 (54.3%) patients with MI who died from cardiogenic shock and/or cardiac rupture. The relative level of enterovirus antigen (RLEVA) in the blood of patients with MI complicated and uncomplicated by cardiogenic shock and/or cardiac rupture was 0.42 +/- 0.04 and 0.29 +/- 0.02 arbitrary units respectively (p = 0.032) compared with 0.21 +/- 0.07 in patients with unstable angina (UA) (p = 0.0001). RLEVA in patients with UA was significantly lower than in those with uncomplicated MI (p < 0.011). RLEVA in necrotized myocardial areas after death from cardiogenic shock (0.54 +/- 0.18) and/or cardiac rupture (0.46 +/- 0.15) was higher than outside MI zones (0.30 +/- 0.14 and 0.26 +/- 0.10 respectively) (p < 0.01). RLEVA in coronary vessels feeding the necrotic zones of patients with MI complicated by cardiogenic shock (0.44 +/- 0.18) was higher (p = 0.03) than in the vessel feeding tissues outside the MI zone (0.29 +/- 0.19). It is concluded that enterovirus infection is a factor of ACS; it is directly involved in its pathogenesis and promotes the development of cardiogenic shock and/or cardiac rupture.

Dose finding in the Ames Salmonella assay.

Threshold dose/concentration values, such as the lowest effective dose, minimum effective dose or the lowest effective concentration (LED, MED or LEC, respectively) are in use as an alternative to the mutagen potency measures based on the 'rate' measurements (e.g., the slope of the initial part of the dose-response curve). In this respect, several statistical procedures for the corresponding so-called 'dose finding' were proposed during the last decades. However, most of them disregard the discrete nature of responses such as the plate colony count in the Ames Salmonella assay. When the plate counts agree with the Poisson assumption, two procedures considered here seem to be appropriate for the dose finding. One is based on the stepwise collapsing of the homogeneous control and dose counts; another consists of constructing the confidence limits for the mutation induction factor (MIF). When the dose and control counts are non-overlapping, the simple 'visual' non-parametric estimation of LED is possible. Applicability and validity of the methods is demonstrated with the two data sets on the mutagenicity of the beta-carboline alkaloid, harmine, and one of the oxidation products of apomorphine.

Similarity pattern analysis in mutational distributions.

The validity and applicability of the statistical procedure - similarity pattern analysis (SPAN) - to the study of mutational distributions (MDs) was demonstrated with two sets of data. The first was mutational spectra (MS) for 697 GC to AT transitions produced with eight alkylating agents (AAs) in the lacI gene of Escherichia coli. The second was a recently summarized data on the distributions of 11562 spontaneous, radiation- and chemical-induced forward mutations in the ad-3 region of heterokaryon 12 of Neurospora crassa. They were analyzed as large two-way contingency tables (CTs) where two kinds of profiles were compared: site (or genotypic class) profiles and origin (or mutagen) profiles. To measure similarity (homogeneity) between any pair of profiles, the relevant sufficient statistics, Kastenbaum-Hirotsu squared distance (KHi(2)), was used. Collapsing the similar profiles into distinct internally homogeneous clusters named 'collapsets' revealed their similarity pattern. To facilitate the procedure, the computer program, COLLAPSE, was elaborated. The results of SPAN for the lacI spectra were found comparable with the results of their previous analysis with two multivariate statistical methods, the factor and cluster analyses. In the ad-3 data set, five collapsets were revealed among origin profiles (OPs): (I) ENU = 4NQO = 4HAQO = FANFT = SQ18506; (II) AF-2 = EI = MMS = DEP; (III) ETO = UV; (IV) AHA = PROCARB; and (V) He ions = protons. Moreover, the previous observation that MDs are dose-dependent was confirmed for X-ray-induced MDs. Profiles induced with the low doses of X-rays are similar to that induced with 85Sr, and profiles induced with the medium X-ray doses to those induced with protons and He ions. Evaluated similarities appear to be rather reasonable: mutagens with similar mode of action induce similar MDs. Similarity pattern revealed among genotypic class profiles (GCPs) seems to be also interpretable. When supplemented with descriptive cluster analysis, SPAN appears to be a fruitful methodology in MS analysis.

Deletogenic activity of 1,2:7,8-diepoxyoctane in the Salmonella typhimurium tester strain TA102.

1,2:7,8-Diepoxyoctane (DEO), whose deletogenic activity was first demonstrated in ad-3 system of Neurospora crassa and then in different species, has been tested in Salmonella typhimurium tester strain TA102 (hisG428(Ochre)). It was confirmed that it is a direct acting mutagen and was found that its activity is stimulated with the S9 mix. Obtained His(+) revertants were screened on their response to the histidine analog, N-(2-thiazolyl)-DL-alanine (ThiAla). Thirty-two percent of spontaneous and 52% of DEO-induced revertants were resistant to the analog while no resistance was observed among those induced with 4-nitroquinoline-N-oxide (4NQO). Resistance to ThiAla was interpreted as due to small deletions surrounding the target TAA codon in hisG428(Ochre). Thus, at least two simple test-systems, ad-3 of N. crassa and hisG428(Ochre) of S. typhimurium, gave compatible results and might be useful in searching of deletogens.

[Population analysis CTG trinucleotide repeats in the myotonin-protein kinase I gene]. / Populiatsionnyi analiz trinukleotidnykh CTG-povtorov v gene miotonicheskoi proteinkinazy I.

CTG trinucleotide repeat length polymorphism within the 3' region of the myotonin protein kinase I (MP-I) gene was examined with the use of the polymerase chain reaction (PCR) technique. A total of 159 DNA samples from healthy donors from five ethnic groups including Russians (n = 33), Azerbaijanians (n = 29), Uzbeks (n = 31), Moldavians (n = 31), and Georgians (n = 35) were analyzed. The number of CTG repeats varied from 5 to 24, and allele distribution was bimodal in all populations; alleles with 6, 7 and 9 repeats were not found. Statistical treatment of the data was performed by the contingency table collapsing procedure. Allele distribution in the populations of Russians, Azerbaijanians, Uzbeks and Georgians appeared to be statistically homogenous and significantly (P < 0.001) different from that in Moldavians as well as in Japanese, African, and Western European populations. High heterozygosity levels of all populations, studied (72-86%) indicate the usefulness of this polymorphism in population and genome fingerprinting studies.

The genetic activity of N6-hydroxyadenine and 2-amino-N6-hydroxyadenine in Escherichia coli, Salmonella typhimurium and Saccharomyces cerevisiae.

The genetic activity of 2-amino-N6-hydroxyadenine or 2-amino-N-hydroxylaminopurine (AHA) and N6-hydroxyadenine or 6-N-hydroxylaminopurine (HAP) was studied in S. typhimurium, E. coli and Saccharomyces cerevisiae strains. AHA was a more potent mutagen for bacteria and a less potent mutagen for yeast than HAP. The mutagenic activity of analogs was not influenced by excision, mutagenic or double-strand DNA repair mutations. On the other hand, the uvrBdel mutation has a drastic effect on the mutagenicity and toxicity of both analogs in the Salmonella strains studied. HAP was a very potent mutagen in yeast with a low capability of inducing mitotic recombination contrary to common mutagens, possessed unique intergenic specificity and was able to induce mutations in diploids at rather high frequency.

[The role of metabolic and regulatory factors in the mutagenic activity of purine derivatives in microorganisms]. / Rol' metabolicheskikh i reguliatornykh faktorov v proiavlenii mutagennoi aktivnosti purinovykh proizvodnykh u mikroorganizmov.

The results concerning analysis of the mutagenic activity of analogues of nitrogen bases are given for Saccharomyces cerevisiae, Streptomyces antibioticus, Bacillus subtilis. The mutagenic activity of purine derivatives depends on their metabolic transformations in cell and on the activity of enzyme systems, involved in regulation of purine biosynthesis. The criterion of selection of purine analogues with genetic activity is proposed for yeasts, based on retroinhibitory ability of analogues of nitrogen bases.

[The use of the polyene-resistant mutation model in Saccharomyces as a test-system for detecting genetically active substances]. / Ispol'zovanie modeli polienrezistentnykh mutatsii u drozhzhei-sakharomitsetov v kachestve test-sistemy dlia vyiavleniia geneticheski aktivnykh veshchestv.

The simple test-system has been developed to register mutagenic activity of different chemicals using a model of forward polyene-resistant mutations in Saccharomyces cerevisiae.

[Genetic activity of base analogs in Salmonella typhimurium and Escherichia coli and Saccharomyces cerevisiae]. / Geneticheskaia aktivnost' analogov osnovanii u bakterii Salmonella typhimurium, Escherichia coli i drozhzhei Saccharomyces cerevisiae.

The study of 6-N-hydroxylaminopurine (HAP) and 2-amino-6-N-hydroxylaminopurine (AHAP) activity in bacteria and the yeast was undertaken. AHAP was found to be more effective as a mutagen in bacteria and HAP--in the yeast. Mutagenic and lethal effects or analogues were independent of excision and mutagenic repair both in bacteria and the yeast. Deletion in uvrB region of Salmonella genome leads to hypersensitivity to lethal and mutagenic action of analogues. Both of the latter only cause reversions of base-substitution but not frameshift mutations. Considering the data obtained and the information from published papers, we proposed that HAP and AHAP exert their mutagenic action, like classical analogues, by means of incorporation into DNA and disturbing the regular replication laws.

[Metabolic activation of promutagens in the yeast-microsome test. II. Activation of cyclophosphamide and 2-aminofluorene]. / Metabolicheskaia aktivatsiia promutagenov v teste drozhzhi-mikrosomy. Soobshchenie II. Aktivatsiiia tsiklofosfamida i 2-aminofluorena.

The effect of recombinogenic and mutagenic activation of promutagens, cyclophosphamide and 2-aminofluorene was studied in S9 mouse liver preparations. Cyclophosphamide was activated to induce reversions of an ochre mutation and heteroallelic reversion in yeast tester strains r2089-15V-P4 and P3288, respectively. Metabolic activation of this chemical was greatly enhanced by pretreatment of mice with AROGLOR--1254. 2-aminofluorene was a potent recombinogen after metabolic activation, but proved a poor inducer of reversions of the ochre mutation. For the stationary yeast cells, activated 2-aminofluorene was shown to be not recombinogenic, while for logarithmic cells grown in galactose medium it was moderately recombinogenic, being highly active in this respect for logarithmic cells grown in glucose medium. We recommend to use these compounds as positive controls for exogenous activation in the yeast/microsome test.