Beverages and Desserts With Therapeutic and Prophylactic Properties Based on Alginate-Containing Biogel From Laminaria -- ``Vitalgar Cardio''

In this research, recipes were developed for beverages and desserts based on ”Vitalgar Cardio”, abiogelthat contains alginate, has therapeutic and prophylactic properties, and was produced from laminaria at the SPC ”Vita-Li” LLC. ”Vitalgar Cardio”, in its liquid form, as well as desserts based on it, is a source of soluble dietary fiber (alginates) and chemical elements such as potassium, magnesium and iodine, and is an adsorbent of various toxins, including radionuclides and heavy metals. The developed products have traditional appeal, with a focus on healthy nutrition, which is currently being promoted among the population. Keywords: Lamibaria, Alginate, Fucoida

A model of evolution with constant selective pressure for regulatory DNA sites

<p>Abstract</p> <p>Background</p> <p>Molecular evolution is usually described assuming a neutral or weakly non-neutral substitution model. Recently, new data have become available on evolution of sequence regions under a selective pressure, e.g. transcription factor binding sites. To reconstruct the evolutionary history of such sequences, one needs evolutionary models that take into account a substantial constant selective pressure.</p> <p>Results</p> <p>We present a simple evolutionary model with a single preferred (consensus) nucleotide and the neutral substitution model adopted for all other nucleotides. This evolutionary model has a rate matrix in which all substitutions that do not involve the consensus nucleotide occur with the same rate. The model has two time scales for achieving a stationary distribution; in the general case only one of the two rate parameters can be evaluated from the stationary distribution. In the middle-time zone, a counterintuitive behavior was observed for some parameter values, with a probability of conservation for a non-consensus nucleotide greater than that for the consensus nucleotide. Such an effect can be observed only in the case of weak preference for the consensus nucleotide, when the probability to observe the consensus nucleotide in the stationary distribution is less than 1/2. If the substitution rate is represented as a product of mutation and fixation, only the fixation can be calculated from the stationary distribution. The exhibited conservation of non-consensus nucleotides does not take place if the elements of mutation matrix are identical, and can be related to the reduced mutation rate between the non-consensus nucleotides. This bias can have no effect on the stationary distribution of nucleotide frequencies calculated over the ensemble of multiple alignments, e.g. transcription factor binding sites upstream of different sets of co-regulated orthologous genes.</p> <p>Conclusion</p> <p>The derived model can be used as a null model when analyzing the evolution of orthologous transcription factor binding sites. In particular, our findings show that a nucleotide preferred at some position of a multiple alignment of binding sites for some transcription factor in the same genome is not necessarily the most conserved nucleotide in an alignment of orthologous sites from different species. However, this effect can take place only in the case of a mutation matrix whose elements are not identical.</p

Assessment of endothelial dysfunction in patients with adrenal tumors during skin thermometry with local heating

ЭНДОТЕЛИАЛЬНАЯ ДИСФУНКЦИЯНАДПОЧЕЧНИКОВ НОВООБРАЗОВАНИЯ /ХИРПРЕДОПЕРАЦИОННОЕ ВЕДЕНИЕ БОЛЬНОГОКОЖНАЯ ТЕРМОМЕТРИЯПОСЛЕОПЕРАЦИОННОЕ ВЕДЕНИЕ БОЛЬНОГОФЕОХРОМОЦИТОМА /ХИРНЕЙРОЭНДОКРИННЫЕ НОВООБРАЗОВАНИЯ /ХИРЦель. Изучить функциональное состояние эндотелия у пациентов с феохромоцитомами и гормононеактивными опухолями надпочечников c помощью кожной термометрии до и после оперативного лечения. Материал и методы. Для выявления эндотелиальной дисфункции и оценки реакции микрососудистого тонуса у 19 пациентов с опухолями надпочечников использовали кожную термометрию с помощью прибора "Микротест" до и после оперативного вмешательства. Определяли индекс тепловой вазодиляции k в эндотелиальном, нейрогенном и миогенном диапазонах. Пациенты были разделены на две группы. В первую вошли пациенты с феохромоцитомой (8), во вторую – с гормононеактивными аденомами и гипертонической болезнью (11). В качестве группы сравнения обследовано 27 практически здоровых людей. Результаты. У пациентов с феохромоцитомами индексы тепловой вазодилятации до операции во всех диапазонах были ниже, чем у практически здоровых лиц, однако разница была значима лишь в миогенном и нейрогенном диапазонах. У пациентов с гормононеактивными опухолями надпочечников в сочетании с артериальной гипертензией имелось достоверное снижение индексов тепловой вазодилятации во всех диапазонах. В раннем послеоперационном периоде у пациентов с феохромоцитомами отмечено значимое повышение показателей индексов тепловой вазодилятации в эндотелиальном и миогенном диапазонах, тенденция к росту – в нейрогенном диапазоне. Установлена сильная положительная взаимосвязь между проведением предоперационной подготовки альфа-2 адреноблокаторами (r=0,74; р=0,04), нормализацией артериального давления в послеоперационном периоде и величиной индекса тепловой вазодилятации в эндотелиальном диапазоне после операции (r=0,75; р=0,03). Заключение. У пациентов с феохромоцитомами, гормононеактивными опухолями надпочечников и артериальной гипертензией имеются признаки нарушения функции эндотелия микрососудистого русла. Предоперационная подготовка и адреналэктомия при феохромоцитомах достоверно улучшают реакцию эндотелия микрососудистого русла в ответ на внешние тепловые раздражители.Objective. To investigate the endothelial dysfunction in patients with adrenal tumors during skin thermometry before and after surgery. Methods. "Microtest", a device for skin thermometry, was used to detect endothelial dysfunction in 19 patients with the adrenal tumors. The index of thermal vasodilation K was calculated for the endothelial, neurogenic and myogenic ranges. The patients were divided into two groups: patients with pheochromocytoma (n=8) and with hormonal inactive adrenal tumors and arterial hypertension (n=11). The comparison group consisted of 27 healthy adults. Results. The patients with pheochromocytoma had lower thermal vasodilatation indices in all ranges in comparison to healthy adults; this difference was significant only in the myogenic and neurogenic ranges. A significant decrease of all indices of thermal vasodilation for patients of the second group was observed. A significant increase in indices of thermal vasodilatation in the endothelial and myogenic ranges was registered in patients with pheochromocytoma as well as the trend to rise in the neurogenic range during the early postoperative period. There was a strong positive association between the normalization of blood pressure in the postoperative period, the preoperative treatment with doxazosin, and the value of the index of thermal vasodilation in the endothelial range after the surgery. Conclusions. All patients with pheochromocytomas, hormone-inactive adrenal tumors and arterial hypertension had the signs of impaired microvascular bed endothelial function. Preoperative treatment and adrenalectomy significantly improve the reaction of the microvascular endothelium in response to external heat stimuli in patients with pheochromocytoma

Experimental approaches to the assessment of potential cardioprotective means with doxorubicin-associated cardiomyopathy

Development of methodological approaches for evaluation of cardioprotective activity of drugs in doxorubicin cardiomyopath

Higher and Lower Order Factor Analyses of the Temperament in Middle Childhood Questionnaire.

The Temperament in Middle Childhood Questionnaire (TMCQ) is a widely used parent-report measure of temperament. However, neither its lower nor higher order structures has been tested via a bottom-up, empirically based approach. We conducted higher and lower order exploratory factor analyses (EFAs) of the TMCQ in a large ( N = 654) sample of 9-year-olds. Item-level EFAs identified 92 items as suitable (i.e., with loadings ≥.40) for constructing lower order factors, only half of which resembled a TMCQ scale posited by the measure\u27s authors. Higher order EFAs of the lower order factors showed that a three-factor structure (Impulsivity/Negative Affectivity, Negative Affectivity, and Openness/Assertiveness) was the only admissible solution. Overall, many TMCQ items did not load well onto a lower order factor. In addition, only three factors, which did not show a clear resemblance to Rothbart\u27s four-factor model of temperament in middle childhood, were needed to account for the higher order structure of the TMCQ

Floating marine macro litter in the Black Sea: Toward baselines for large scale assessment

The Black Sea is a semi-enclosed basin subject to major anthropogenic pressures, including marine litter and plastic pollution. Due to numerous large rivers draining into the basin and a population settled along the coast, the region could accumulate significant amounts of floating litter over time. Until now, only limited field data were available, and litter quantities and distribution remained unknown. In this study, floating marine macro litter (FMML) was assessed at the regional Black Sea scale for the first time, showing relatively high litter densities across the basin that reached a weighted mean of 81.5 items/km(2). Monitoring data revealed an accumulation of floating items offshore in the eastern part of the basin, resembling on a small scale a "garbage patch', where litter items were trapped, showing elevated densities in comparison to their surrounding areas. Most of these items were made of plastic materials (ca. 96%) and included large numbers of plastic and poly-styrene fragments of small size ranges (2.5-10 cm). Harmonised field data collection through consistent and regular monitoring programmes across the region is essential to establish baselines and thresholds for large scale assessment at international level

Adverse reactions of high-osmolar and low-osmolar radiographic contrast media in clinical practice

Introduction. Adverse drug reactions (ADR) to administration of radiographic contrast media (RCM) are observed in 10–20 % of patients. Individual tolerability of drugs is affected by RCM properties (ionicity, osmolarity). Aim. Evaluation of ADR in patients during diagnostic studies using high- and low-osmolar RCM. Methods. Analysis of 52 reports of adverse reactions to RCM registered in medical organizations of Voronezh region in 2014–2021 was performed. Group 1 included 21 patients with ADR to high-osmolar RCM (sodium amidotrizoate, yoxitalamic acid), group 2–31 patients with ADR to low-osmolar drugs (yogexol, yopromide, yopamidol, yoversol). Results. Age of patients is 6–82 years, median 48.5 years, children — 8 persons (15.4 %), women — 31 patients (59.6 %), serious reactions — 28 (53.8 %). Since 2017 there has been an increase in the number of ADRs with constant frequency of serious reactions. In 2020–2021 ADRs to low-osmolar drugs were mainly registered. Life-threatening conditions (anaphylactic shock, arterial hypotension, arrhythmia) were observed in 70.2 % of group 2, in 28.6 % of group 1 (p=0.007). One patient with initial renal dysfunction and comorbid pathology was reported to develop nephrotoxicity to yogexol. Pharmacological correction was performed in 92.3 % of cases. In 57.7 % of the patients ADR ended in recovery, in the  other cases — state improvement. Conclusion. Side effects of high-osmolar and low-osmolar RCM mainly had form of hyperergic reactions of immediate type and were reversible. High frequency of serious reactions to lowosmolar RCM against an increase in their use requires a more careful selection of patients for X-ray contrast studies

Чувствительность барорецепторов и состояние автономной нервной системы у пациентов с хроническими нарушениями сознания

Purpose of the study: to examine sensibility of baroreceptors and the autonomic nervous in the passive orthostatic test in patients with chronic impairment of consciousness due to severe brain damage and determine their role in the rehabilitation process.Materials and methods. The study included 30 patients with long-term impairment of consciousness due to severe brain damage (group 1), 10 of them being in the vegetative state (VS) and 20 being in the minimally conscious state (MCS). Craniocerebral trauma was the main cause of severe damage in that group (53% of patients). The comparison group included 24 patients with focal neurological symptoms caused predominantly — 79.2% of cases — by cerebrovascular disorders (group 2). The control group (group 3) consisted of 22 healthy volunteers of a comparable age. All measurements were done with the help of a Task Force Monitor 1030i (CNSystem, Austria) in the course of passive orthostatic test at 0°–30°–60°–0°. Changes in the power of low-frequency (LFS) and highfrequency spectrum (HFS) of heart rate variability and baroreceptors sensibility (BRS) were analyzed. Statistical analysis was carried out using Statistica-10 software. Significance of inter-group differences on unrelated samples was determined by the Mann–Whitney U-test. Differences between groups were considered significant at P 0.05.Results. Maximal background values of BRS were found in the control group. In group 1 and 2 patients, considerable decrease of that index was noted, which was proportional to the brain damage severity. Similar dynamics was observed for the indices of autonomic nervous system sensibility (LFS and HFS). The main trend of orthostatic changes of BRS, LFS, and HFS was characterized by progressive decrease of the indices with increase of the patients’ angle of tilting and their return to the baseline level after the patients were put back into the horizontal position. 4 patients of group 1 (14%) displayed signs of orthostatic disorders upon tilting to 30°: in 3 cases, orthostatic hypotension was observed, and in one case the postural orthostatic tachycardia syndrome (POTS) was diagnosed. Those patients differed by lower BRS and higher sympathetic system activity (LFS) vs. the same indices of other patients in that group.Conclusion. Patients with chronic impairment of consciousness during the post-comatose period after a severe brain damage display a significant decrease of baroreceptors sensibility and autonomic nervous system disorders manifesting in significantly lower activity of the sympathetic and parasympathetic systems. The prominence of such disorders is associated with brain damage severity. Their risk of developing orthostatic hypotension during tilting towards a vertical position is higher in patients who have lower baroreceptors sensibility, and this should be taken into account beginning the process of their verticalization.Цель исследования: изучить чувствительность барорецепторов и автономной нервной системы при пассивной ортостатической пробе у пациентов с хроническими нарушениями сознания вследствие тяжелых повреждений головного мозга и определить их роль в реабилитационном процессе.Материалы и методы. В исследование включили 30 пациентов с длительными нарушениями сознания, вызванными тяжелыми повреждениями головного мозга (группа 1), 10 из которых были в вегетативном состоянии (ВС) и 20 — с синдромом малого сознания (СМС). Основной причиной тяжелых повреждений была черепно-мозговая травма (53% пациентов этой группы). В группу сравнения вошли 24 пациента с очаговой неврологической симптоматикой, основной причиной которой в 79,2% случаев были нарушения мозгового кровообращения (группа 2). Контрольную группу (группа 3) составили 22 здоровых добровольца сопоставимого возраста. Все измерения проводили с помощью монитора Task Force Monitor 1030i (CNSystem, Австрия) в процессе пассивной ортостатической пробы 0°–30°–60°–0°. Провели анализ изменений показателей мощности низкочастотного (НЧС) и высокочастотного спектров (ВЧС) вариабельности сердечного ритма и чувствительности барорецепторов (ЧБР). Статистический анализ провели с помощью пакета статистических программ «Statistica-10». Значимость межгрупповых различий несвязанных выборок определяли расчетом критерия Манна Уитни (Mann–Whitney U-test). Достоверными считали различия при достижении уровня статистической значимости p 0,05.Результаты. Максимальные фоновые значения ЧБР выявили в контрольной группе. У пациентов 1 и 2 групп отмечали значительное снижение этого показателя, пропорциональное тяжести повреждений головного мозга. Аналогичную динамику имели показатели чувствительности автономной нервной системы (НЧС и ВЧС). Основной тренд ортостатических изменений ЧБР, НЧС, ВЧС характеризовался прогрессивным снижением этих показателей при увеличивающемся угле наклона пациентов и с восстановлением их до исходного уровня после возврата пациентов в горизонтальное положение. У 4 пациентов группы 1 (14%) при выполнении наклона на 30° появились признаки ортостатических нарушений: в 3 случаях наблюдали ортостатическую гипотензию и в одном — синдром постуральной ортостатической тахикардии (СПОТ). Отличием этих пациентов были более низкая ЧБР и более высокие показатели активности симпатической системы (НЧС) по сравнению с показателями других пациентов данной группы.Заключение. У пациентов с хроническими нарушениями сознания в посткоматозном периоде после тяжелых повреждений головного мозга наблюдаются значительное снижение чувствительности барорецепторов и нарушения автономной нервной системы, выражающиеся в значительном снижении активности симпатической и парасимпатической систем. Степень этих нарушений ассоциирована с тяжестью повреждений головного мозга. Риск развития ортостатической гипотензии при вертикализации выше у пациентов с более низкой чувствительностью барорецепторов, что необходимо учитывать в начале процесса их вертикализации

Considerations for the Bioanalytical Part of Equivalence Studies of Biosimilar Nadroparin Calcium

According to current regulatory views, a comparative study of the pharmacodynamics (PD) of low molecular weight heparin (LMWH) products and confirmation of their equivalence require comparing three PD markers: the anti-Xa activity, the anti-IIa activity, and the tissue factor pathway inhibitor (TFPI) concentration. The aim of this study was to analyse the features specific to the bioanalytical part of an equivalence study of a nadroparin calcium biosimilar after single subcutaneous administration. Material and methods: the anti-Xa and anti-IIa activity values and TFPI content were determined in human plasma samples obtained after single subcutaneous administration of the test and the reference product in the same dose, using commercially available reagent kits and pre-validated assays. The authors calculated the main PD parameters (surrogate pharmacokinetic markers), namely the maximum activity or concentration (Amax or Cmax), time to maximum activity or concentration (Tmax), area under the activity–time (or concentration–time) curve (AUC ), and half-life period (T1/2), by means of model-independent statistical moment analysis and carried out further statistical testing of the parameters. Results: the anti-Xa activity and TFPI concentration results provided for  the  possibility  of  calculating  and  comparing  the PD parameters (Amax or Cmax, AUC0-24, AUC0-∞, Tmax, T1/2) and estimating the confidence intervals that are necessary to confirm the bioequivalence of the studied products. The anti-IIa activity data had a characteristic pattern of slight fluctuations around one level, which prevented the calculation and comparison of PD parameters. Conclusion: the study identified specific features to consider when planning comparative PD studies of nadroparin calcium products. Firstly, it is feasible to divide samples into two test aliquots (one for anti-Xa and anti-IIa activity determination, the other for TFPI analysis) at the moment of collection in order to perform the analytical step correctly. Secondly, there is no need in full validation for the bioanalytical assays of the anti-Xa and anti-II activity and TFPI content in human plasma validated in the concentration ranges of 0.024–0.182 IU/mL, 0.0069–0.052 IU/mL and 1.56–100 ng/mL, respectively; a confirmation that the active ingredient does not interfere with the analytical procedure is adequate for the purpose. Finally, the data obtained may not allow for calculating PD parameters and comparing confidence intervals for all three markers. The listed considerations may be relevant for other LMWH products as well

Evidence of the Generation of Isosaccharinic Acids and Their Subsequent Degradation by Local Microbial Consortia within Hyper-Alkaline Contaminated Soils, with Relevance to Intermediate Level Radioactive Waste Disposal

The contamination of surface environments with hydroxide rich wastes leads to the formation of high pH (>11.0) soil profiles. One such site is a legacy lime works at Harpur Hill, Derbyshire where soil profile indicated in-situ pH values up to pH 12. Soil and porewater profiles around the site indicated clear evidence of the presence of the α and β stereoisomers of isosaccharinic acid (ISA) resulting from the anoxic, alkaline degradation of cellulosic material. ISAs are of particular interest with regards to the disposal of cellulosic materials contained within the intermediate level waste (ILW) inventory of the United Kingdom, where they may influence radionuclide mobility via complexation events occurring within a geological disposal facility (GDF) concept. The mixing of uncontaminated soils with the alkaline leachate of the site resulted in ISA generation, where the rate of generation in-situ is likely to be dependent upon the prevailing temperature of the soil. Microbial consortia present in the uncontaminated soil were capable of surviving conditions imposed by the alkaline leachate and demonstrated the ability to utilise ISAs as a carbon source. Leachate-contaminated soil was sub-cultured in a cellulose degradation product driven microcosm operating at pH 11, the consortia present were capable of the degradation of ISAs and the generation of methane from the resultant H2/CO2 produced from fermentation processes. Following microbial community analysis, fermentation processes appear to be predominated by Clostridia from the genus Alkaliphilus sp, with methanogenesis being attributed to Methanobacterium and Methanomassiliicoccus sp. The study is the first to identify the generation of ISA within an anthropogenic environment and advocates the notion that microbial activity within an ILW-GDF is likely to influence the impact of ISAs upon radionuclide migration