Dynamics Of Disease Development Research Articles

Two myeloproliferative diseases in one patient - co-occurence of clones

Classical myeloproliferative diseases can be divided into Philadelphia chromosome-positive chronic myeloid leukemia and Philadelphia chromosome-negative myeloproliferative neoplasm. The driver mutations of the latter occur in the Janus kinase 2 or calreticulin genes. The coincidence of Philadelphia chromosome-negative and -positive myeloproliferative neoplasms in the same patient is exceptionally rare in the literature. During the long-term follow-up of our 120 patients with chronic myeloid leukemia, we investigated the clinical data of patients in whom Philadelphia chromosome-negative myeloproliferative disease was also confirmed. Philadelphia chromosome was detected by classical cytogenetic methods and/or fluorescence in situ hybridization. The amount of BCR-ABLI fusion RNA was monitored by quantitative real-time polymerase chain reaction. Mutations in the Janus kinase 2 and calreticulin genes were detected by quantitative allele-specific polymerase chain reaction and fragment analysis. The dynamics of disease development were inferred from the change in the amount of mutant clones over time and from the clinical data. We identified four cases carrying both Philadelphia chromosome and Janus kinase 2/calreticulin gene mutation. In some cases, competition between the clones, in other cases their co-occurrence in a common clone was observed. Isolated thrombocytosis at the time of diagnosis or persisting thrombocytosis during targeted therapy with good molecular response may call attention to the possibility of the co-occurrence of the two diseases. Co-occurrence of Philadelphia chromosome-positive and -negative myeloproliferative neoplasms is more frequent than the literature suggests. If the disease has an unusual appearance, the association of the two myeloproliferative dieseases may be suspected.

The efficiency of using small-volume spraying in chemical protection of grapes from diseases in the conditions of Crimea

The article presents the results of studies carried out in 2020-2021 in soil and climatic conditions of the Mountain-Valley viticultural zone of Crimea to determine the efficiency of small-volume spraying in pest control of industrial vineyards of wine grape variety ‘Muscat Rose’. In experimental variant, when using small-volume spraying, the amount of working solution and the rate of pesticide application were reduced (operations on the concentration of working solution). It was established that against the background of protective measures of grape plantings in experimental and example (full-volume spraying) variants, a low level of oidium development was observed: up to 1.3% on leaves, 1.1% on bunches; and of black rot - up to 1.2% on bunches. At the same time, there was no significant difference in the intensity and dynamics of disease development in these variants. It was experimentally determined that in the experiment, when using small-volume (200-250 l/ha) and full-volume (example, 400-800 l/ha) sprayings, a good conditional yield of wine grapes ‘Muscat Rose’ was obtained - 2.5-2.6 kg/bush (52.4-54.7 c/ha). The use of full-volume and small-volume sprayings on experimental plots did not have a negative effect on the process of sugar accumulation (25.1-25.5 g/100 cm3) and the level of titratable acids (6.0-6.2 g/dm3) in grape yield. Thus, in the course of studies, it was found that using of small-volume spraying made it possible to increase the productivity of sprayers and reduce the pesticide load on ampelocenosis.

Metabolic Modeling Combined With Machine Learning Integrates Longitudinal Data and Identifies the Origin of LXR-Induced Hepatic Steatosis.

Temporal multi-omics data can provide information about the dynamics of disease development and therapeutic response. However, statistical analysis of high-dimensional time-series data is challenging. Here we develop a novel approach to model temporal metabolomic and transcriptomic data by combining machine learning with metabolic models. ADAPT (Analysis of Dynamic Adaptations in Parameter Trajectories) performs metabolic trajectory modeling by introducing time-dependent parameters in differential equation models of metabolic systems. ADAPT translates structural uncertainty in the model, such as missing information about regulation, into a parameter estimation problem that is solved by iterative learning. We have now extended ADAPT to include both metabolic and transcriptomic time-series data by introducing a regularization function in the learning algorithm. The ADAPT learning algorithm was (re)formulated as a multi-objective optimization problem in which the estimation of trajectories of metabolic parameters is constrained by the metabolite data and refined by gene expression data. ADAPT was applied to a model of hepatic lipid and plasma lipoprotein metabolism to predict metabolic adaptations that are induced upon pharmacological treatment of mice by a Liver X receptor (LXR) agonist. We investigated the excessive accumulation of triglycerides (TG) in the liver resulting in the development of hepatic steatosis. ADAPT predicted that hepatic TG accumulation after LXR activation originates for 80% from an increased influx of free fatty acids. The model also correctly estimated that TG was stored in the cytosol rather than transferred to nascent very-low density lipoproteins. Through model-based integration of temporal metabolic and gene expression data we discovered that increased free fatty acid influx instead of de novo lipogenesis is the main driver of LXR-induced hepatic steatosis. This study illustrates how ADAPT provides estimates for biomedically important parameters that cannot be measured directly, explaining (side-)effects of pharmacological treatment with LXR agonists.

Thermovaccination – thermoheliox as a stimulator of the immune response. Kinetics of the synthesis of antibodies and C-reactive protein in coronavirus infection

Clinical trials of thermoheliox application (inhalation with a high-temperature mixture of oxygen and helium, 90 °C) in the treatment of the acute phase of coronavirus infection were conducted. Dynamics of disease development in infected patients (PCR test for the virus) and, dynamics of changes in blood concentration of C-reactive protein, immunoglobulin M, specific immunoglobulin G were studied. High efficiency of thermoheliox in releasing the organism from the virus and stimulating the immune response (thermovaccination effect) was shown. The kinetic model of the process is proposed and analyzed.

Pear rust: peculiarities of pathogen biology measures for control and profilactic

Pear rust: peculiarities of pathogen biology measures for control and profilactic

Morphology and Morphometry of the Lung in Corn Snakes (Pantherophis guttatus) Infected with Three Different Strains of Ferlavirus

Ophidian paramyxovirus (ferlavirus) is a global threat to reptilian sauropsids in herpetological collections, with occasional but fatal effects. This study characterizes the effects of three different genetic strains of ferlavirus on the dynamic changes of histology and morphometry of the lung of corn snakes (Pantherophis guttatus). Lungs from 42 corn snakes were either sham-infected or infected experimentally under standardized conditions. From 4 to 49 days after intratracheal inoculation, the lungs were examined qualitatively and quantitatively. Progressive microscopical changes were seen in the lung. Initially, increased numbers of heterophils were observed in the interstitium followed by proliferation and vacuolation of epithelial cells lining faveoli. Electron microscopy revealed loss of type-I pneumocytes, hyperplasia of type-II pneumocytes, and interstitial infiltrates of heterophils and mononuclear cells. With progression of disease the respiratory epithelium was initially overgrown by transformed type-II pneumocytes and later became multilayered. The results of the study suggest that the respiratory capacity of the lungs declines with disease development. The dynamics of disease development and histopathology differed in snakes infected with different ferlavirus genogroups. Animals infected with virus genogroup B developed histopathological changes and morphometric changes more rapidly and of greater intensity than snakes infected with viruses from genogroups A or C.

A New Strategy for Analyzing Time-Series Data Using Dynamic Networks: Identifying Prospective Biomarkers of Hepatocellular Carcinoma.

Time-series metabolomics studies can provide insight into the dynamics of disease development and facilitate the discovery of prospective biomarkers. To improve the performance of early risk identification, a new strategy for analyzing time-series data based on dynamic networks (ATSD-DN) in a systematic time dimension is proposed. In ATSD-DN, the non-overlapping ratio was applied to measure the changes in feature ratios during the process of disease development and to construct dynamic networks. Dynamic concentration analysis and network topological structure analysis were performed to extract early warning information. This strategy was applied to the study of time-series lipidomics data from a stepwise hepatocarcinogenesis rat model. A ratio of lyso-phosphatidylcholine (LPC) 18:1/free fatty acid (FFA) 20:5 was identified as the potential biomarker for hepatocellular carcinoma (HCC). It can be used to classify HCC and non-HCC rats, and the area under the curve values in the discovery and external validation sets were 0.980 and 0.972, respectively. This strategy was also compared with a weighted relative difference accumulation algorithm (wRDA), multivariate empirical Bayes statistics (MEBA) and support vector machine-recursive feature elimination (SVM-RFE). The better performance of ATSD-DN suggests its potential for a more complete presentation of time-series changes and effective extraction of early warning information.

FEATURES OF THE CHRONIC PAIN SYNDROME IN PATIENTS WITH RHEUMATOID ARTHRITIS AND MEDICAL DIAGNOSTIC TACTICS

Objective: to establish features of a chronic pain syndrome disorders in patients with rheumatoid arthritis, to reveal correlation with psychoemotional disorders and to develop the differential approach to maintaining patients. Materials and methods. 101 patients at the age of 60.6 ± 11.8 years, 92 % of women, with reliable rheumatoid arthritis (American College of Rheumatology – ACR, 1987), were examined. The visual analog scale was used for an assessment of pain strength at the moment; the Van Korff’s questionnaire – for determination of pain strength at the moment and retrospectively for the last half a year with an assessment of disadaptation level and disability, ranging of a chronic pain syndrome on classes; the McGill Pain Questionnaire – for the characteristic of touchsensitive and emotional components of pain. Neuropathic pain was revealed by DN4 questionnaire. Anxiety and depression were determined by the Hospital Anxiety and Depression Scale (HADS). Fibromyalgia diagnosed by criteria of ACR, (1990). Results. Pain estimated by various scales and questionnaires varied from moderated to intensive. According to Van Korff’s questionnaire it was characterized by average level of disadaptation and easy disability that corresponded to the second class of chronic pain. The Rank pain index of the McGill Pain Questionnaire touch scale testified that pain was described by a smaller number of definitions on a touch scale than on emotional. This indicates a moderate impact of pain syndrome on a state of mind. Neuropathic pain is diagnosed for 37.3 % of patients with tunnel syndrome, mononeuritis and touch polyneuropathy. The secondary fibromyalgia is revealed for 2 % of patients with early rheumatoid arthritis of high activity. According to HADS anxiety and depression was revealed for 58 and 59 % of patients correspondingly. This demanded psychotherapeutic consultation and additional correction. We proposed the algorithm of diagnostic and medical tactics for rheumatoid arthritis patients with a chronic pain syndrome in therapeutic practice based on pain strength gradation, assessment of chronic pain syndrome variations, definition of anxiety and depression signs. All this allows to validate consultation of medical specialists and to differentiate treatment. Conclusions. The integrated approach to diagnostics of a chronic pain syndrome for rheumatoid arthritis allows to estimate pain strengths in dynamics of disease development, to reveal existence of pain variations, anxiety and depression. It enables usage of patient maintenance tactics and increases efficiency of treatment in therapeutic practice.

0527: Changing in level of microRNA-1, –155, –210, –208a and –499 in blood plasma, platelets and monocytes of patients with ST-segment-elevation myocardial infarction

The study of the changing levels of microRNAs (miRNAs) in different biological body environments as diagnostic and prognostic marker for ST-elavation myocardial infarction (STEMI) calls attention of scientists. We conducted a research to determine the level of several microRNAs in blood plasma, isolated monocytes and platelets of STEMI pts in the dynamics of disease development (the 1st and the 7th days). Into the study we included the evaluation of some cardiac microRNAs (1, 208a, 208b, 499), inflammation-related and hypoxic-response microRNA-155 and –210. 20 STEMI pts (mean age 54,85±2,2 years) were identified in National Scientific Center Institute of Cardiology M.D. Strazhesko. The control group included 10 subjects of comparable sex and age without any evidence of coronary artery disease. Expression miRNAs was quantified from plasma, isolated monocytes and platelets using quantitative Real-Time polymerase-chain reaction system. In plasma the microRNA-1 level was significantly higher only on day 7, the microRNA-155 level was lower on the first day and 15 times higher on day 7. In platelets the microRNA-1 level was 4.2 times higher on the first day of STEMI in comparison with the control group and on day 7 of STEMI returned to the level of the control group. The changes in monocytes were more revealing: the microRNA-1 level was higher by 28 times on the first day of STEMI, the microRNA-208a level was higher by 2 times on day 1 and by 19 times on day 7 of STEMI, and the microRNA-155 level was higher by 17 times on day 1 and by 260 times on day 7 of STEMI in comparison to the control group. The miRNA distribution is unique amongst blood plasma, isolated monocytes and platelets in pts with STEMI. Our results show higher informational content of evaluation of certain miRNAs in isolated cells comparing with blood plasma, and expresses the necessity of determining miRNA levels in the dynamics of STEMI.

Fungal foliar plant pathogen epidemics: modelling and qualitative analysis

A new approach for modelling epidemics caused by fungal foliar plant pathogens is presented. The model is described by a system of differential equations, and is simple enough to allow a qualitative analytical study of the main epidemiological factors that determine the rate of disease progress during a single growing period. The model was analysed and compared with Vanderplank's basic equations of plant disease development and some of Jeger's models. Results of qualitative investigation of the model, and close similarity between simulated and observed dynamics of disease development, show that this new approach may be used to compare and analyse some foliar fungal disease epidemics in more detail than formerly.