MULTIMORBID AND POLYPHARMACY IN CLINICAL CARDIOLOGY IN TERMS OF THE CLINICAL CASE

In this article is raised the topic of multimorbidity and polypharmacy on the example of a clinical case with the main diagnosis of Ischemic Heart Disease: Systemic atherosclerosis with predominance of coronary arteries sclerosis. Stable angina class III. Hypertensive heart disease III stage 3rd degree. Aortocoronary bypass. Sick sinus syndrome, tachy-brady form. Constant form of atrial fibrillation-flutter. AV node catheter ablation with pacemaker implantation. Infarction pneumonia of the lingual segments of the upper lobe of the right lung. CHF II-B stage with preserved systolic function of the left ventricle (EF LV 53 %). Very high additional cardiovascular risk. Concomitant conditions: Chronic obstructive pulmonary disease: Chronic obstructive bronchitis 2 degrees severity. Chronic pulmonary insufficiency III degree. Obesity III degree. Diabetes mellitus type 2, medium severity, decompensated. Chronic renal failure, III stage. The ongoing therapy is discussed and recommendations are given to minimize it in order to avoid polypharmacy

The selection pressure on the neuraminidase gene of influenza viruses isolated in Ukraine from 2009 to 2015

A broad range of naturally occurring antigenic variants of the influenza virus is caused by its rapid evolutionary variability. The survival of viable influenza virus variants occurs through natural selection. The treatment of influenza infection with modern antiviral drugs – neuraminidase (NA) inhibitors – leads to the occurrence of mutations in the NA gene, which thereby result in the emergence of virus resistance to these drugs. The goal of this study was to determine the selection pressure on the NA protein of influenza viruses isolated in Ukraine from 2009 to 2015. The main method for assessing the selection pressure on proteins is to quantify the ratio of substitution rates at nonsynonymous (dN) and synonymous (dS) sites. With the help of this method, we showed that only a few codons in the NA gene were under positive selection resulting in mutations at the following sites: for influenza A viruses of the A(H1N1)pdm09 subtype – site 40, for viruses of the A(H3N2) subtype – sites 93 and 402, for Influenza B viruses of the B/Yamagata lineage – sites 74, 99, and 268, and for the viruses of the B/Victoria lineage – sites 358, 288, and 455. These sites are not associated with the NA active site, transmembrane domain, or the antigenic sites of this protein. We concluded that NA inhibitors are not a significant factor in the process of selection of the influenza viruses in Ukraine because the sites associated with the resistance of influenza viruses to NA inhibitors were not affected by positive selection. This finding could be explained by the limited use of NA inhibitors for the treatment of influenza infections in Ukraine. A broad range of naturally occurring antigenic variants of the influenza virus is caused by its rapid evolutionary variability. The survival of viable influenza virus variants occurs through natural selection. The treatment of influenza infection with modern antiviral drugs – neuraminidase (NA) inhibitors – leads to the occurrence of mutations in the NA gene, which thereby result in the emergence of virus resistance to these drugs. The goal of this study was to determine the selection pressure on the NA protein of influenza viruses isolated in Ukraine from 2009 to 2015. The main method for assessing the selection pressure on proteins is to quantify the ratio of substitution rates at nonsynonymous (dN) and synonymous (dS) sites. With the help of this method, we showed that only a few codons in the NA gene were under positive selection resulting in mutations at the following sites: for influenza A viruses of the A(H1N1)pdm09 subtype – site 40, for viruses of the A(H3N2) subtype – sites 93 and 402, for Influenza B viruses of the B/Yamagata lineage – sites 74, 99, and 268, and for the viruses of the B/Victoria lineage – sites 358, 288, and 455. These sites are not associated with the NA active site, transmembrane domain, or the antigenic sites of this protein. We concluded that NA inhibitors are not a significant factor in the process of selection of the influenza viruses in Ukraine because the sites associated with the resistance of influenza viruses to NA inhibitors were not affected by positive selection. This finding could be explained by the limited use of NA inhibitors for the treatment of influenza infections in Ukraine.

Genetic control of scald resistance in barley landraces

Scald (Rhynchosporium secalis (Oudem.) J.J. Davis pathogenic agent) is one of the most harmful barley diseases. A high variability of this fungi explains the occurrence of new aggressive pathotypes and, accordingly, loss of cultivar resistance. It was found that many recently selected varieties of barley and previously identified sources of resistance to R. secalis are now susceptible to the pathogen. There is only one gene, Rrs9, that maintains efficiency against pathogen populations in Russia. The aim of this study is to find donors of genes for effective resistance to scald with the ability to easily transfer this trait for hybridization. The inheritance of scald resistance in 33 barley landraces was studied. Analysis of the interaction between the pathogen test clones and the host plant revealed a difference between the alleles determining fungal resistance in 32 barley forms, the previously effective genes Rrs4, rrs6, rrs7, and currently effective Rrs9. It was found that 30 accessions are protected by new unidentified genes for scald resistance. Accessions k-18398 and k-16231 from China are likely to possess allelic genes for scald resistance, while the gene (or genes) of accession k-31075 from Nepal is allelic to the Rrs9 gene. It was demonstrated by hybridological analysis that accessions k-3307, k-15868, k-18989 and k-3481 are protected by effective genes for scald resistance, which differ from each other and which are not allelic to the Rrs4, rrs6, rrs7 or Rrs9 genes. Accessions k-15868 and k-3481 possess two complementary recessive genes for scald resistance, k-18989 has two recessive genes, and k-3307 carries one recessive gene for pathogen resistance. The resistance genes of these forms are manifested during all the stages of plant ontogenesis

Juvenile resistance of barleys from the East Asian center of crop origin and domestication to powdery mildew

Background. A significant reduction in the yield of barley may be provoked by powdery mildew (causative agent: Blumeria graminis (DC.) Golovin ex Speer f. sp. hordei Marchal). A vast majority of cultivars approved for use in Russia are susceptible to the pathogen. Including genotypes protected by previously unused resistance genes into breeding practice is necessary to ensure the national food security. Barley landraces could become a fairly rich source of replenishment for the bank of effective pathogen resistance genes.Materials and methods. The study covered 950 barley accessions from the East Asian center of crop origin and domestication: 449 accessions from Japan, 313 from China, 173 from Mongolia, and 15 from Nepal. The experiments were carried out on young plants in a climatic chamber under artificial infection conditions. The northwestern (Pushkin, St. Petersburg) population of B. graminis served as an inoculum. Plant resistance was assessed using a scoring scale. The resistance of the selected forms was assessed twice.Results and conclusions. Significant variability of barley accessions from the countries of East Asia in their resistance to powdery mildew was observed. Symptoms of the disease were not found on plants of 16 studied forms. Weak or moderate development of the B. graminis mycelium was recorded for 21 accessions. Twenty-seven accessions were heterogeneous in the studied trait. Various levels of resistance were identified in 64 studied accessions (6.73%), among which 44 represented cultivars and breeding lines, and 20 were landraces. The percentage of accessions susceptible to the studied population of the pathogen was 93.27%

LOCAL BARLEY ACCESSIONS FROM ETHIOPIA RESISTANT TO POWDERY MILDEW

The mlo11 allele associated with the loss of function of the Mlo locus and controlling mildew resistance in the majority of modern barley cultivars was identified in Ethiopian barley landraces. Twenty-seven accessions from Ethiopia were studied during laboratory experiments which resulted in identifying k-5448 as an accession resistant to powdery mildew. Three accessions (k-8555, k-8682 k-17554) were heterogeneous by the studied trait. With the help of molecular markers we showed that the resistant components of the selected forms are protected by the mlo11 gene

Identification of barley accessions from the VIR collection carrying the <i>mlo11(cnv2)</i> powdery mildew resistance allele

Background. The search for barley (Hordeum vulgare L.) genotypes that carry effective genes for resistance to powdery mildew agent Blumeria graminis f. sp. hordei is a present-day issue for Russian plant breeding. The mlo11 allele that confers long-term protection of barley against the pathogen is rarely found among the varieties, approved for cultivation in the territory of Russia. There is no information on the occurrence among Russian varieties of another effective allele, mlo11 (cnv2), therefore, the search for its source is a current necessity. Materials and methods. Seven barley accessions from Ethiopia and 7 accessions from Japan have been tested for resistance to the northwestern population of the powdery mildew agent in the field and in laboratory conditions. To identify of the Mlo gene alleles, nucleotide sequences of the Stowaway-MITE (Miniature Inverted-repeat Transposable Elements) and the adjacent promoter fragments were determined. Results. Phytopathological tests in the field and greenhouse conditions, as well as molecular markers were used to study 14 barley accessions from Ethiopia and Japan. According to the preliminary tests, plants were resistant to powdery mildew. The highly effective allele of powdery mildew resistance mlo11 (cnv2) was for the first time identified in four barley accessions from Ethiopia, k-20087, k-20523, k-20524 and k-28126. Under field conditions, adult plants were resistant, and in the greenhouse they were moderately damaged by powdery mildew (1-2 points). The disease symptoms were similar to those described for the sample Eth295, a carrier of the mlo11(cnv2) allele variant: single pustules and the absence of necrotic spots on the leaves. The fragments of Stowaway-MITE and adjacent Mlo 5' promoter sequences were amplified in all 14 accessions. The amplicons were cloned and sequenced. The unique marker SNPs within the MITE and Mlo 5’ promoter sequences, i.e. the substitutions of cytosine by thymine in positions 262 and 452, were found only in k-20087, k-20523, k-20524 and k-28126. These accessions belong to different botanical varieties and differ from each other in a number of morphological features, i.e. they are not duplicates. Conclusions. The genotypes selected as a result of the study can serve as a source of the mlo11(cnv2) allele in breeding powdery mildew-resistant barley varieties

Resistance of barley cultivars approved for use in Russia to harmful organisms and toxic aluminum ions

Background. The most rational way to reduce barley crop losses from diseases, pests and adverse edaphic factors is cultivation of resistant varieties. The specificity of the host– pathogen interactions necessitates a constant search for new donors of resistance for breeding, and phytosanitary monitoring of cultivars.Materials and methods. The research material comprised 248 barley cultivars included in the State Register of Selection Achievements Admitted for Usage in the Russian Federation – 168 were developed domestically, and 80 by foreign breeders. Their resistance to powdery mildew and leaf rust was studied in under laboratory and field conditions. Barley cultivars distinguished for powdery mildew resistance were analyzed using molecular markers. In the laboratory, barley was screened for greenbug resistance. To study the sensitivity to toxic aluminum ions in barley, we used the laboratory method for the early diagnosis of the trait – the root test method.Results and conclusions. Field and laboratory screening revealed a fairly wide diversity of barley cultivated in Russia in terms of resistance to harmful organisms and the edaphic stressor. It was established that 24 barley cultivars were resistant to powdery mildew, and 14 accessions were carriers of the effective mlo11 allele. Two cultivars manifested combined resistance to powdery mildew and barley leaf rust. In 11 cultivars, a distinct greenbug resistance was revealed. High resistance to toxic aluminum ions according to the root and sprout length indices was observed in 26 cultivars. Accessions with the complex resistance to harmful organisms and the edaphic stressor were identified

Powdery mildew resistance of barley in Southern Dagestan

Background. The most effective way of protecting crops from diseases and pests is the breeding and cultivation of resistant varieties. The hydrothermal regime in the southern plains of Dagestan favors damage to barley plants by the causative agent of powdery mildew. The high level of disease progress observed annually helps to reliably assess the resistance of collection accessions to the pathogen.Materials and methods. The research material included 1361 barley accessions (570 improved cultivars and 791 landraces) of different ecogeographic origin and growth habit. Field experiments were launched concurrently with winter sowing. Powdery mildew resistance was scored during the heading period and in the milk ripeness phase using a point scale. Each accession was assessed for at least three years.Results and conclusions. The results of a long-term study disclosed a significant intraspecific variability of barley collection accessions in their resistance to powdery mildew. A significant part of the studied barley accessions (63.1%) appeared susceptible to the pathogen. The occurrence frequency of disease-resistant accessions was 11.0%, while those with medium resistance reached 25.9%. Among the landraces, four resistant accessions from the Abyssinian, West Asian and Mediterranean centers of crop origin were identified. Seventeen barley varieties resistant to powdery mildew (predominantly originated from Western Europe) are recommended for use in breeding for immunity

Genetic diversity of barley accessions from East Asian countries in terms of resistance to powdery mildew

Background. Barley is an ancient crop currently cultivated in more than 100 countries. High adaptability makes it possible to cultivate it in environments unfavorable for many other crops. At the same time, fungal diseases can have a negative impact on its grain yield and quality. One of the most harmful is the fungus Blumeria graminis (DC.) Golovin ex Speer f. sp. hordei Marchal. The pathogen can overcome a cultivar’s resistance, resulting in significant harvest losses. There is a need for a constant search for new effective sources of resistance to powdery mildew for barley breeding.Materials and methods. A set of 950 barley accessions from the East Asian center of the crop’s morphogenesis were studied at the adult stage of plant development. They were screened and crossed in the fields of Pushkin and Pavlovsk Laboratories of VIR (St. Petersburg, Russia). Genetic control of barley resistance to B. graminis was analyzed in a climate chamber under artificial infection pressure with the northwestern population of the fungus. Scoring scales were used for screening.Results and conclusions. Weak development of B. graminis during the heading phase was observed on plants of 38 barley accessions from the East Asian center. High resistance at all stages of development was manifested by 20 genotypes that can be used in breeding programs. Resistance genes in 18 selected forms differed in their effectiveness at the seedling stage of development and during the heading phase. Accessions k-3433, k-10931, k-10934, k-11608, k-17545, k-20272, k-20279, k-20354 and k-27867 had one dominant resistance gene each. Accessions k-11608, k-12278, and k-17545 are protected by the identical gene, while the resistance of k-3433 is induced by a gene that differs from the genes present in accessions k-10931 and k-20279

Alternaria leaf blight of clusterbean

The annual  legume  crop clusterbean (Cyamopsis tetragonoloba  (L.) Taub.) is a promising  crop for cultivation  in the south of Russia. In 2018, phytosanitary examinations of clusterbean fields (13 collection accessions) were conducted in five VIR branches (Krasnodar Territory, Dagestan,  Astrakhan and Volgograd Regions). At all points,  several types of leaf spots were observed on clusterbean leaves and symptoms of plant damage by fungi of the genus  Alternaria Nees prevailed.  Using microbiological  methods and  Next-Generation Sequencing (NGS) of the  nuclear  ribosomal internal  transcribed spacer  two (ITS2), the  species  composition of micromycetes was identified.  It was found  that the  micromycetes Alternaria spp. in different  ecological  and  geographical conditions of the  south  of Russia cause two main types of leaf spots: the typical (beige and brown round spots, usually accompanied by concentric zonality) and brown  spot (small brown  bulging  merging spots). Overwhelmingly  the damage to leaf tissues is caused  by the fungus  A. tenuissima (Nees &amp; T. Nees : Fr.) Wiltshire. A quite  numerous accompanying mycoflora (first of all, fungi of the genus  Fusarium Link) was also detected. A. cyamopsidis Rangaswami &amp; A.V. Rao, one of the most  harmful guar pathogens in the countries  where the main acreage is located  (India, Pakistan, USA), was not found on clusterbean fields in Russia. The accessions  of clusterbean differ in degree of damage by A. tenuissima that causes Alternaria leaf blight. Differential interaction of parasite  and plant  host was revealed.  Therefore, to prevent epiphytotics, varieties protected by non-identical resistance genes  should  be grown.  At all VIR branches, accessions  k-52568 (Argentina) and k-52569 (Pakistan) were weakly damaged by Alternaria leaf blight, and some  accessions  were resistant only in the environmental conditions of one or two experimental stations. The accessions  studied were heterogeneous  in pathogen resistance,  which  allows selecting  disease-resistant lines from most  of the  collection  accessions.  Thus, in various VIR branches, plants  without symptoms of disease  were selected from accessions  k-52571, k-52573 and k-52580, and seeds were collected to create new donors of disease resistance