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Мета. Оцінити ефективність хірургічного лікування пацієнтів з первинним гіперальдостеронізмом (ПГА). Матеріали і методи. За період з 2014 по лютий 2018 р. в клініці госпітальної хірургії Запорізького державного медичного університету у 46 пацієнтів діагностували ПГА, оперативне лікування проведено 23 пацієнтам, серед них 15 (65%) жінок і 8 (35%) чоловіків. Середній вік пацієнтів становив (52,3 ± 9,5) року. За даними комп’ютерної (КТ) та магнітно-резонансної ( МРТ) томографії правобічна локалізація аденом надниркових залоз встановлена у 10 (43,5%) пацієнтів, лівобічна - у 7 (30,4%), двобічна - у 6 (26,1%). Розмір об’ємних утворень надниркових залоз становив (18,3 ± 6,7) мм. Діагностику проводили згідно з Клінічними практичними рекомендаціями з діагностики та лікування первинного гіперальдостеронізму (Clinical Practical Guideline - The Management of Primary Aldosteronism; 2008, 2016). Оперативне лікування проводили з використанням ендоскопічних методів. Лапароскопічну адреналектомію виконали 19 (82,6%) пацієнтам, лапароскопічну резекцію надниркової залози - 4 (17,4%). Результати оперативного лікування оцінювали згідно зі стандартними та клініко-біохімічними критеріями PASO (Primary Aldosteronism Surgical Outcomes). Результати. Тривалість операцій становила в середньому 150 (120 - 200) хв, строки лікування пацієнтів у стаціонарі - (9 ± 2,1) доби. До конверсій не вдавалися, післяопераційних ускладнень не було. Ніхто з пацієнтів не помер. Порівняльний аналіз результатів оперативного лікування показав статистично достовірне зниження показників систолічного артеріального тиску (САТ), діастолічного артеріального тиску (ДАТ), концентрації альдостерону та підвищення рівня калію (p < 0,05). Кореляційний аналіз не виявив статистично достовірного зв’язку між концентрацією альдостерону та масою міокарда лівого шлуночка (ММЛШ), товщиною міжшлуночкової перегородки (ТМШП), товщиною задньої стінки лівого шлуночка (ТЗСЛШ) у пацієнтів до та після оперативного лікування. Клінічні результати хірургічного лікування пацієнтів з ПГА, оцінені за критеріями PASO та стандартними критеріями, практично схожі: повне одужання констатовано у 39,2 та 43,5% пацієнтів, часткове - у 60,8 та 56,5% пацієнтів відповідно; біохімічні результати, оцінені аналогічно, суттєво різнилися: повне одужання - 91,3 та 43,5%, часткове - 8,7 та 56,5% відповідно. Висновки. В хірургічному лікуванні пацієнтів з аденомами надниркових залоз, що супроводжуються ПГА, слід надавати перевагу лапароскопічним методам (адреналектомія, резекція). Ефективність мініінвазивних методів хірургічного лікування ПГА статистично достовірна. Клініко-біохімічні критерії PASO в оцінці результатів хірургічного лікування пацієнтів з ПГА мають перевагу перед стандартними, оскільки є комплексними. Після хірургічного лікування пацієнтів з ПГА повне біохімічне одужання настає у 91,3% пацієнтів, повне клінічне - у 39,2%, часткове біохімічне - у 8,7%, часткове клінічне - у 60,8% пацієнтів.

Abstract Background Gene trees carry important information about specific evolutionary patterns which characterize the evolution of the corresponding gene families. However, a reliable species consensus tree cannot be inferred from a multiple sequence alignment of a single gene family or from the concatenation of alignments corresponding to gene families having different evolutionary histories. These evolutionary histories can be quite different due to horizontal transfer events or to ancient gene duplications which cause the emergence of paralogs within a genome. Many methods have been proposed to infer a single consensus tree from a collection of gene trees. Still, the application of these tree merging methods can lead to the loss of specific evolutionary patterns which characterize some gene families or some groups of gene families. Thus, the problem of inferring multiple consensus trees from a given set of gene trees becomes relevant. Results We describe a new fast method for inferring multiple consensus trees from a given set of phylogenetic trees (i.e. additive trees or X-trees) defined on the same set of species (i.e. objects or taxa). The traditional consensus approach yields a single consensus tree. We use the popular k-medoids partitioning algorithm to divide a given set of trees into several clusters of trees. We propose novel versions of the well-known Silhouette and Caliński-Harabasz cluster validity indices that are adapted for tree clustering with k-medoids. The efficiency of the new method was assessed using both synthetic and real data, such as a well-known phylogenetic dataset consisting of 47 gene trees inferred for 14 archaeal organisms. Conclusions The method described here allows inference of multiple consensus trees from a given set of gene trees. It can be used to identify groups of gene trees having similar intragroup and different intergroup evolutionary histories. The main advantage of our method is that it is much faster than the existing tree clustering approaches, while providing similar or better clustering results in most cases. This makes it particularly well suited for the analysis of large genomic and phylogenetic datasets.

Circulating miRNAs are increasingly being considered as biomarkers in various medical contexts, but the value of analyzing isomiRs (isoforms of canonical miRNA sequences) has not frequently been assessed. Here we hypothesize that an in-depth analysis of the full circulating miRNA landscape could identify specific isomiRs that are stronger biomarkers, compared to their corresponding miRNA, for identifying increased CV risk in patients with non-alcoholic fatty liver disease (NAFLD)—a clinical unmet need. Plasma miRNAs were sequenced with next-generation sequencing (NGS). Liver fat content was measured with magnetic-resonance spectrometry (MRS); CV risk was determined, beyond using traditional biomarkers, by a CT-based measurement of coronary artery calcium (CAC) score and the calculation of a CAC score-based CV-risk percentile (CAC-CV%). This pilot study included n = 13 patients, age > 45 years, with an MRS-measured liver fat content of ≥5% (wt/wt), and free of overt CVD. NGS identified 1103 miRNAs and 404,022 different isomiRs, of which 280 (25%) and 1418 (0.35%), respectively, passed an abundance threshold. Eighteen (sixteen/two) circulating miRNAs correlated positively/negatively, respectively, with CAC-CV%, nine of which also significantly discriminated between high/low CV risk through ROC-AUC analysis. IsomiR-ome analyses uncovered 67 isomiRs highly correlated (R ≥ 0.55) with CAC-CV%. Specific isomiRs of miRNAs 101-3p, 144-3p, 421, and 484 exhibited stronger associations with CAC-CV% compared to their corresponding miRNA. Additionally, while miRNAs 140-3p, 223-3p, 30e-5p, and 342-3p did not correlate with CAC-CV%, specific isomiRs with altered seed sequences exhibited a strong correlation with coronary atherosclerosis burden. Their predicted isomiRs-specific targets were uniquely enriched (compared to their canonical miRNA sequence) in CV Disease (CVD)-related pathways. Two of the isomiRs exhibited discriminative ROC-AUC, and another two showed a correlation with reverse cholesterol transport from cholesterol-loaded macrophages to ApoB-depleted plasma. In summary, we propose a pipeline for exploring circulating isomiR-ome as an approach to uncover novel and strong CVD biomarkers. [ABSTRACT FROM AUTHOR]

In this, work some aspects of the development of the visual system of Nothobranchius guentheri at the main stages of ontogenesis were described for the first time. It was possible to establish that the formation of the visual system occurs similarly to other representatives of the order Cyprinodontiformes, but significantly differs in terms of the individual stages of embryogenesis due to the presence of diapause. In the postembryonic period, there is a further increase in the size of the fish’s eyes and head, to the proportions characteristic of adult fish. The histological structure of the eye in adult N. guentheri practically does not differ from most teleost fish living in the same environmental conditions. The study of the structure of the retina showed the heterogeneity of the thickness of the temporal and nasal areas, which indicates the predominant role of peripheral vision. Morphoanatomical measurements of the body and eyes of N. guentheri showed that their correlation was conservative. This indicates an important role of the visual system for the survival of fish in natural conditions, both for the young and adults. In individuals of the older age group, a decrease in the amount of sodium (Na) and an increase in magnesium (Mg) and calcium (Ca) were found in the eye lens. Such changes in the elemental composition of the lens can be a sign of the initial stage of cataractogenesis and disturbances in the metabolism of lens fibers as a result of aging. This allows us to propose N. guentheri as a model for studying the structure, formation, and aging of the visual and nervous systems.

Civilizational development entails the formation of a contradiction between the technosphere and the biosphere, with the consequences of greenhouse effects; it is carried out within the framework of technological structures independent of socio-economic formations. Governing bodies and activities that provide significant growth (or control planetary environmental safety) are key factors, as are technological innovations, with industry and consumption playing a key role in the spread of a new technological order. The technosphere, as the main product of civilizational development, has gone through a number of pre-industrial and at least five industrial technological modes and will most likely move into the sixth (post-industrial) technological mode. The main causes of greenhouse gases are gas emissions, methane, and ozone. The rise in the 20th century of the temperature on the surface of the planet is a result of a reaction to anthropogenic emissions of gases, including accidental oxides, tropospheric ozone and its "expectations", halogenated hydrocarbons, nitrogen oxides, etc. [ABSTRACT FROM AUTHOR]

Objective: In obesity, adipocyte hypertrophy is detrimental to health, but its' interrelation with fibrosis in the visceral adipose tissue (VAT) depot remains unclear. Because VAT is less accessible via biopsy, biomarkers for VAT quality are needed. The authors hypothesized that VAT adipocyte size and fibrosis are interrelated and can be estimated by circulating microRNAs (circ‐miRNAs), contributing to subphenotyping obesity. Methods: Adipocyte size and AT fibrosis were estimated in n = 43 participants (BMI ≥ 30 kg/m2). Circ‐miRNAs were sequenced (Next Generation Sequencing). Results: Participants with above‐ versus below‐median VAT adipocyte area exhibited metabolic dysfunction but lower total and pericellular fibrosis. VAT adipocyte size remained associated with metabolic dysfunction even when controlling for BMI or VAT fibrosis in the entire cohort, as in matched‐pairs subanalyses. Next Generation Sequencing uncovered 22 and 6 circ‐miRNAs associated with VAT adipocyte size and fibrosis, respectively, with miRNA‐130b‐3p common to both analyses. The combination of miRNA‐130b‐3p + miR‐150‐5p + high‐density lipoprotein cholesterol discriminated among those with large versus small VAT adipocytes (receiver operating characteristic‐area under the curve: 0.872 [95% CI: 0.747–0.996]), whereas miRNA‐130b‐3p + miRNA‐15a‐5p + high‐density lipoprotein cholesterol discriminated among those with low and high fibrosis (receiver operating characteristic‐area under the curve: 0.823 [95% CI: 0.676–0.97]). Conclusions: These findings suggest that VAT adipocyte size and fibrosis are inversely correlated in obesity and can be estimated by distinct circ‐miRNAs, providing a potential tool to subphenotype obesity via a liquid biopsy‐like approach to assess VAT health in nonsurgical patients. [ABSTRACT FROM AUTHOR]

A synthetic strategy for obtaining structurally flexible hybrid iron(II) carboranoclatrochelates functionalized with biorelevant groups, based on a combination of a 1,3-dipolar cycloaddition reaction with nucleophilic substitution of an appropriate chloroclathrochelate precursor, was developed. In its first stage, a stepwise substitution of the dichloroclathrochelate precursor with amine N-nucleophiles of different natures in various solvents was performed. One of its two chlorine atoms with morpholine or diethylamine in dichloromethane gave reactive monohalogenoclathrochelate complexes functionalized with abiorelevant substituents. Further nucleophilic substitution of their remaining chlorine atoms with propargylamine in DMF led to morpholine- and diethylamine-functionalized monopropargylamine cage complexes, the molecules of which contain the single terminal C≡C bond. Their “click” 1,3-cycloaddition reactions in toluene with ortho-carborane-(1)-methylazide catalyzed by copper(II) acetate gave spacer-containing di- and tritopic iron(II) carboranoclatrochelates formed by a covalent linking between their different polyhedral(cage) fragments. The obtained complexes were characterized using elemental analysis, MALDI-TOF mass, UV-Vis, 1H, 1H{11B}, 11B, 11B{1H}, 19F{1H} and 13C{1H}-NMR spectra, and by a single crystal synchrotron X-ray diffraction experiment for the diethylamine-functionalized iron(II) carboranoclathrochelate. Its encapsulated iron(II) ion is situated almost in the center of the FeN6-coordination polyhedron possessing a geometry intermediate between a trigonal prism and a trigonal antiprism with a distortion angle φ of approximately 28°. Conformation of this hybrid molecule is strongly affected by its intramolecular dihydrogen bonding: a flexibility of the carborane-terminated ribbed substituent allowed the formation of numerous C–H…H–B intramolecular interactions. The H(C) atom of this carborane core also forms the intermolecular C–H…F–B interaction with an adjacent carboranoclathrochelate molecule. The N–H…N intermolecular interaction between the diethylamine group of one hybrid molecule and the heterocyclic five-membered 1H-[1,2,3]-triazolyl fragment of the second molecule of this type caused formation of H-bonded carboranoclathrochelate dimers in the X-rayed crystal.

Introduction. The problem of primary aldosteronism (PA) different forms diagnosis and treatment is absolutely interesting in the 21st century as over the last 15 years it has been proved that PA syndrome had been distributed much more than previously thought. It accounts for 10-15% of all cases of hypertension. Aim: to analyze the diagnostic and treatment of patients with bilateral lesions of adrenal glands (AG) with PA. Materials and Methods. During the period from 2014 to March 2017 year 14 patients with bilateral lesions of AG with PA have been examined and treated at the clinic. 8 (57.1%) were women and 6 (42.9%) were men. The average age of patients was 55,6±11,9 years. Adenomas of AG were diagnosed in 6 (42.9%) of cases, hyperplasia of AG in 8 (57.1%). We measured the concentration of aldosterone, renin, adrenocorticotropic hormone, cortisol in plasma, levels of potassium and sodium, loading tastes, night dexamethasone suppression test, computer tomography and adrenal vein sampling (AVS). Surgical treatment was performed in 7 (50%) of patients - in 3 cases (21.4%) it was the laparoscopic adrenalectomy (LAE) and in 1 case (7.2%) – the laparoscopic resection of the adrenal gland (LRAG), for 3 (21.4%) patients endovascular destruction of the AG (EVD) was performed. Conservative therapy including aldosterone antagonists was prescribed for 7 (50%) patients. Results and Discussion. Indication for the surgical treatment or REVD was a gradient of lateralization rated 3:1 and more. If the gradient was below a specified value, the result was regarded as idiopathic aldosteronism (IA) and aldosterone antagonists (verospiron, eplerenonum) with control of K+ concentration level were used. We believe that in case with bilateral adenomas of AG, if there are no conditions for the AG resection, it is necessary to perform LAE of functionally more active gland. It helps to stabilize the level of blood pressure without antihypertensive drugs prescription or with reducing of their dosage and to achieve the hormonal status normalization. REVD is used in cases of unilateral hyperplasia of AG with hypersecretion. In case of IA using of this treatment method is inappropriate, as the therapy has temporary effect, which is demonstrated by relapse of aldosterone and blood pressure level increasing. We use EVD in IA treatment to reduce the dosages of aldosterone antagonists. Conclusions. AVS with calculation of aldosterone-cortisol ratio with a negative dexamethasone suppression test is the crucial point for diagnosis. Preference should be given to LRAG with saving adrenal central vein as surgical treatment. In case of IA the therapy starts from aldosterone antagonists prescription with dosage titration. EVD should be used for reduction of drugs large doses. primary hiper aldosteronism; adrenal vein sampling; adenoma; nodular hyperplasia; endovascular destruction