Search

The objectives of this study were to conduct a systematic review of the literature to determine the optimal treatment method for patients with atlanto-occipital dislocation (AOD) and to identify possible factors influencing their outcomes.We conducted a systematic review of the PubMed database between January 1966 and December 2020. The main inclusion criterion was articles that discussed AOD treatment methods, and outcome descriptions were selected for analysis. Intergroup differences were assessed using nonparametric statistical methods.Of the 657 articles identified initially, only 54 met the inclusion criteria, resulting in data from 139 patients. Type I or II AODs were more frequent in patients injured in road traffic accidents, whereas type III AODs were more frequent in patients with catatrauma (P = 0.027). Spinal cord injury was more frequently observed in patients with types I and II AODs than in those with type III AOD (P = 0.026). Improved outcomes were more common in the surgical treatment group (P 0.001). Significant differences in treatment outcomes between the halo device and orthosis groups were not observed (P = 0.32).Prognosis of AOD is unfavorable in adults with dislocations resulting from road traffic accidents, those with types I and II AOD, and patients younger than 22 years and older than 47 years. Surgical treatment was optimal for adult patients with an AOD, and treatment outcomes did not depend on the number of occipitocervical fusion levels. Immobilization with the halo device showed no advantages over use of an external orthosis.

A gamma-pyrone derivative, comenic acid, activates the opioid-like receptor-mediated signaling pathway that modulates the NaV1.8 channels in the primary sensory neuron membrane. These channels are responsible for the generation of the nociceptive signal; therefore, gamma-pyrones have great therapeutic potential as analgesics, and this effect deserves a deeper understanding. The novelty of our approach to the design of a medicinal substance is based on a combination of the data obtained from living neurons using very sensitive physiological methods and the results of quantum chemical calculations. This approach allows the correlation of the molecular structure of gamma-pyrones with their ability to evoke a physiological response of the neuron. Comenic acid can bind to two calcium cations. One of them is chelated by the carbonyl and hydroxyl functional groups, while the other forms a salt bond with the carboxylate anion. Calcium-bound gamma-pyrones have fundamentally different electrostatic properties from free gamma-pyrone molecules. These two calcium ions are key elements involved in ligand-receptor binding. It is very likely that ion-ionic interactions between these cations and anionic functional groups of the opioid-like receptor activate the latter. The calculated intercationic distance of 9.5 Å is a structural criterion for effective ligand-receptor binding of calcium-bound gamma-pyrones.

In this paper, the history, present status, and future of density-functional theory (DFT) is informally reviewed and discussed by 70 workers in the field, including molecular scientists, materials scientists, method developers and practitioners. The format of the paper is that of a roundtable discussion, in which the participants express and exchange views on DFT in the form of 300 individual contributions, formulated as responses to a preset list of 26 questions. Supported by a bibliography of 776 entries, the paper represents a broad snapshot of DFT, anno 2022.

Development of original methodological approaches to annotation and labeling of histological images in relation to the problem of automatic segmentation of the layers of the stomach wall.Three image collections were used in the study: NCT-CRC-HE-100K, CRC-VAL-HE-7K, and part of the PATH-DT-MSU collection. The used part of the original PATH-DT-MSU collection contains 20 histological images obtained using a high performance digital scanning microscope.Each image is a fragment of the stomach wall, cut from the surgical material of gastric cancer and stained with hematoxylin and eosin. Images were obtained using a scanning microscope Leica Aperio AT2 (Leica Microsystems Inc., Germany), annotations were made using Aperio ImageScope 12.3.3 (Leica Microsystems Inc., Germany).A labeling system is proposed that includes 5 classes (tissue types): areas of gastric adenocarcinoma (TUM), unchanged areas of the lamina propria (LP), unchanged areas of the muscular lamina of the mucosa (MM), a class of underlying tissues (AT), including areas of the submucosa, own muscular layer of the stomach and subserous sections, image background (BG). The advantage of this marking technique is to ensure high efficiency of recognition of the muscularis lamina (MM) - a natural «line» separating the lamina propria of the mucous membrane and all other underlying layers of the stomach wall. The disadvantages of the technique include a small number of classes, which leads to insufficient detailing of automatic segmentation.In the course of the study, an original technique for labeling and annotating images was developed, including 5 classes (types of tissues). This technique is effective at the initial stages of teaching mathematical algorithms for the classification and segmentation of histological images. Further stages in the development of a real diagnostic algorithm to automatically determine the depth of invasion of gastric cancer require the correction and development of the presented method of marking and annotation.Разработка оригинальных методических подходов к аннотированию и разметке гистологических изображений применительно к задаче автоматической сегментации слоев стенки желудка.В исследовании использовали три коллекции изображений: NCT-CRC-HE-100K, CRC-VAL-HE-7K и часть коллекции PATH-DT-MSU. Используемая часть оригинальной коллекции PATH-DT-MSU содержит 20 гистологических изображений, полученных с использованием высокопроизводительного цифрового сканирующего микроскопа. Каждое изображение представляет собой фрагмент стенки желудка, вырезанный из операционного материала по поводу рака желудка и окрашенный гематоксилином и эозином. Изображения получены с помощью сканирующего микроскопа Leica Aperio AT2 (Leica Microsystems Inc., Германия), аннотации сделаны с использованием Aperio ImageScope 12.3.3 (Leica Microsystems Inc., Германия).Предложена система разметки, включающая 5 классов (типов тканей): участки аденокарциномы желудка (TUM), неизмененные участки собственной пластинки слизистой оболочки (LP), неизмененные участки мышечной пластинки слизистой оболочки (MM), класс подлежащих тканей (АТ), включающий участки подслизистой основы, собственный мышечный слой желудка и субсерозные отделы, фон изображения (BG). К преимуществу данной методики разметки относится обеспечение высокой эффективности распознавания мышечной пластинки — естественной «линии», разделяющей собственную пластинку слизистой оболочки и все другие подлежащие слои стенки желудка. Недостатки методики: небольшое количество классов, что приводит к недостаточной детализации автоматической сегментации.В ходе исследования разработана оригинальная методика разметки и аннотирования изображений, включающая 5 классов (типов тканей). Данная методика эффективна на начальных этапах обучения математических алгоритмов классификации и сегментации гистологических изображений. Дальнейшие этапы разработки реального диагностического алгоритма в целях автоматического определения глубины инвазии рака желудка требуют корректировки и развития представленной методики разметки и аннотации.

To present the technique of extra-intracranial bypass surgery using the orifice of maxillary artery bypass, to evaluate the advantages and disadvantages of this and alternative revascularization options.Radial artery graft harvesting was performed at the 1st stage. Simultaneously, the second team of surgeons performed a combined (submandibular and anterior) access to the donor artery (mandibular segment of maxillary artery behind the ramus of the mandible). Craniotomy and mobilization of potential recipient arteries (M2-M3 segments of the middle cerebral artery) were performed at the 2nd stage. Distal anastomosis in end-to-side fashion was formed with M3 segment of the middle cerebral artery. At the 3rd stage, radial artery was passed through a subcutaneous tunnel in zygomatic region. The orifice of maxillary artery was resected together with distal external carotid artery (ECA) and orifice of superficial temporal artery. After transposition of ECA and orifice of maxillary artery, proximal end-to-end anastomosis was performed with radial artery. After that, the main surgical stage was performed, i.e. exclusion of M3 segment of the middle cerebral artery together with aneurysm.Harvesting of mandibular segment of the maxillary artery as a donor vessel reduces the length of bypass graft to 12-14 cm since this branch is localized close to the skull base. You can also form optimal proximal end-to-end anastomosis for intracranial redirecting blood flow maxillary artery.The described method makes it possible to form anastomosis with a short bypass graft and reduce the risk of thrombosis. This procedure is effective for cerebral bypass in patients with skull base tumors, complex aneurysms, and occlusive-stenotic lesions of carotid arteries.Представить методику обходного шунтирования сосудов головного мозга с использованием устья верхнечелюстной артерии, оценить достоинства и недостатки данной методики и альтернативных вариантов реваскуляризации.На 1-м этапе произведено выделение графта из лучевой артерии. Одновременно второй бригадой хирургов выполнен комбинированный (поднижнечелюстной и предушный) доступ к артерии-донору — нижнечелюстному сегменту верхнечелюстной артерии (ВЧА) за ветвью нижней челюсти. На 2-м этапе произведены краниотомия и выделение потенциальных артерий реципиентов (сегменты М2—М3 средней мозговой артерии — СМА). Осуществлен дистальный анастомоз по классической методике с сегментом М3 СМА по типу «конец в бок». На 3-м этапе лучевая артерия проведена в подкожном тоннеле в скуловой области. Устье ВЧА резецировано вместе с дистальным отделом наружной сонной артерии (НСА) и устьем поверхностной височной артерии. После транспозиции НСА и устья ВЧА выполнен проксимальный анастомоз с лучевой артерией по типу «конец в конец». После этого выполнен основной этап операции — выключение сегмента М3 средней мозговой артерии вместе с аневризмой.Представленная методика выделения и использования в качестве донора наиболее крупной из конечных ветвей НСА — нижнечелюстного сегмента ВЧА, расположенного близко к основанию черепа, позволяет сократить длину обходного шунта до 12—14 см и выполнить проксимальный анастомоз по оптимальной методике «конец в конец» с целью перенаправления всего потока крови из ВЧА интракраниально.Применение разработанного авторами статьи способа позволяет в более комфортных условиях для хирурга сформировать анастомоз с относительно короткой рабочей частью шунта и, соответственно, с меньшим риском его тромбоза. Метод обеспечивает эффективное заместительное шунтирование головного мозга у пациентов с опухолями основания черепа, сложными аневризмами и окклюзионно-стенотическим поражением сонных артерий.

In molecular-stream separation (MSS), a stream of a multi-component mixture is separated into multiple streams of individual components. Quantitative evaluation of MSS data has been a bottleneck in MSS for decades as there was no conventional way to present the data in a reproducible and uniform fashion. The roots of the problem were in the multi-dimensional nature of MSS data; even in the ideal case of steady-state separation, the data is three-dimensional: intensity and two spatial coordinates. We recently found a way to reduce the dimensionality via presenting the MSS data in a polar coordinate system and convoluting the data via integration of intensity along the radius axis. The result of this convolution is an angulagram — a simple 2D plot presenting integrated intensity vs angle. Not only does an angulagram simplify the visual assessment, but it also allows the determination of three quantitative parameters characterizing the quality of MSS: stream width, stream linearity, and stream deflection. Reliably converting an MSS image into an angulagram and accurately determining the stream parameters requires an advanced and user-friendly software tool. In this technical note, we introduce such a tool: the open-source software Topino available at https://github.com/Schallaven/topino. Topino is a stand-alone program with a modern graphical user interface that allows processing an MSS image in a fast ( p { margin-bottom: 0.25cm; direction: ltr; line-height: 115%; text-align: left; orphans: 2; widows: 2 }a:link { color: #0000ff }

Intracranial aneurysms (IAs) pose a high risk of spontaneous subarachnoid hemorrhage. In the most complex cases, the only way to exclude the aneurysm from the circulation is to perform a high-flow extracranial-to-intracranial bypass, thus creating a new bloodstream. This avoids severe ischemic complications; however, it requires careful consideration of individual anatomy and hemodynamic parameters. Computational fluid dynamics (CFD) can be of great help in planning such a surgery by creating 3D patient-specific models of cerebral circulation.Assessment of the perspectivity of high-flow extracranial-to-intracranial bypass planning using computational modeling.In this research work, we have applied the CFD methods to a patient with a giant thrombosed IA of the internal carotid artery (ICA). Preoperative CTA images and Gamma Multivox workstation were used to create a 3D model with current geometry and three additional models: Normal anatomy (no IA), Occlusion (with ligated ICA), Virtual bypass (with bypass and ligated ICA). The postoperative data were also available. Boundary conditions were based on PC-MRI measurements. Calculation of hemodynamics was conducted with a finite element package ANSYS Workbench 19.The results demonstrated an increase in the blood flow on the affected side by more than 70% after the virtual surgery and uniformity of flow distribution between the affected and contralateral sides, indicating that the treatment is likely to be efficient. Later, postoperative data confirmed that.The study showed that virtual preoperative CFD modeling could significantly simplify and improve surgical planning.Наличие интракраниальных аневризм (ИА) сопряжено с высоким риском субарахноидального кровоизлияния. В наиболее сложных случаях единственным способом выключения аневризмы из кровотока является реваскуляризация пораженного бассейна путем создания обходного высокопоточного экстра-интракраниального шунта. Данный подход позволяет избежать тяжелых ишемических осложнений, однако необходим тщательный учет индивидуальных анатомических и гемодинамических параметров пациента. Вычислительная гидродинамика (computational fluid dynamics — CFD) может оказать существенную помощь в планировании подобных операций, позволяя создавать пациентспецифичные трехмерные модели мозгового кровообращения.Оценить возможности планирования обходного высокопоточного экстра-интракраниального шунтирования с помощью средств компьютерного моделирования.В настоящем исследовании мы применили методы компьютерного моделирования в случае пациента с гигантской тромбированной ИА внутренней сонной артерии (ВСА). На основании данных предоперационной компьютерной томографической ангиографии (КТА) построена 3D-модель церебральных артерий пациента с текущей геометрией и три дополнительные модели: «Нормальная анатомия» (без ИА), «Окклюзия» (с лигированной ВСА), «Виртуальное шунтирование» (с шунтированием и лигированной ВСА). Кроме того, построена модель, основанная на послеоперационных данных. Скорости кровотока, используемые в качестве граничных условий, измерены с помощью фазово-контрастной магнитно-резонансной томографии. Расчет гемодинамики проведен в конечно-элементном программном комплексе ANSYS Workbench 19.Продемонстрировано увеличение кровотока на пораженной стороне более чем на 70% после виртуальной операции, а также достижение равномерности распределения кровотока между пораженной и контралатеральной сторонами, что указывает на предположительную эффективность лечения. Результаты моделирования совпали с послеоперационными данными.Исследование показало, что виртуальное предоперационное CFD-моделирование может значительно упростить планирование операции и повысить эффективность хирургического лечения.

Chemoresistance, i.e., tumor insensitivity to chemotherapy, shortens life expectancy of cancer patients. Despite the availability of new treatment options, initial systemic regimens for solid tumors are dominated by a set of standard chemotherapy drugs, and alternative therapies are used only when a patient has demonstrated chemoresistance clinically. Chemoresistance predictors use laboratory parameters measured on tissue samples to predict the patient's response to chemotherapy and help to avoid application of chemotherapy to chemoresistant patients. Despite thousands of publications on putative chemoresistance predictors, there are only about a dozen predictors that are sufficiently accurate for precision oncology. One of the major reasons for inaccuracy of predictors is inaccuracy of analytical methods utilized to measure their laboratory parameters: an inaccurate method leads to an inaccurate predictor. The goal of this study was to identify analytical challenges in chemoresistance-predictor development and suggest ways to overcome them. Here we describe principles of chemoresistance predictor development via correlating a clinical parameter, which manifests disease state, with a laboratory parameter. We further classify predictors based on the nature of laboratory parameters and analyze advantages and limitations of different predictors using the reliability of analytical methods utilized for measuring laboratory parameters as a criterion. Our eventual focus is on predictors with known mechanisms of reactions involved in drug resistance (drug extrusion, drug degradation, and DNA damage repair) and using rate constants of these reactions to establish accurate and robust laboratory parameters. Many aspects and conclusions of our analysis are applicable to all types of disease biomarkers built upon the correlation of clinical and laboratory parameters.

Cytometry of Reaction Rate Constant (CRRC) uses time-lapse fluorescence microscopy to measure a rate constant of a catalytic reaction in individual cells and, thus, facilitate accurate size determination for cell subpopulations with distinct efficiencies of this reaction. Reliable CRRC requires uniform exposure of cells to the reaction substrate followed by their uniform imaging, which in turn, requires that a tissue sample be disintegrated into a suspension of dispersed cells, and these cells settle on the support surface before being analyzed by CRRC. We call such cells "dispersed-settled" to distinguish them from cells cultured as a monolayer. Studies of the dispersed-settled cells can be tissue-relevant only if the cells maintain their 3D tissue state during the multi-hour CRRC procedure. Here, we propose an approach for assessing tissue relevance of the CRRC-based analysis of the dispersed-settled cells. Our approach utilizes cultured multicellular spheroids as a 3D cell model and cultured cell monolayers as a 2D cell model. The CRRC results of the dispersed-settled cells derived from spheroids are compared to those of spheroids and monolayers in order to find if the dispersed-settled cells are representative of the spheroids. To demonstrate its practical use, we applied this approach to a cellular reaction of multidrug resistance (MDR) transport, which was followed by extrusion of a fluorescent substrate from the cells. The approach proved to be reliable and revealed long-term maintenance of MDR transport in the dispersed-settled cells obtained from cultured ovarian cancer spheroids. Accordingly, CRRC can be used to determine accurately the size of a cell subpopulation with an elevated level of MDR transport in tumor samples, which makes CRRC a suitable method for the development of MDR-based predictors of chemoresistance. The proposed spheroid-based approach for validation of CRRC is applicable to other types of cellular reactions and, thus, will be an indispensable tool for transforming CRRC from an experimental technique into a practical analytical tool.

The development of new types of fungicides for agriculture and medicine is highly desirable due to the uprising fungal resistance against commonly used compounds. Herein, 4-substituted-4-nitropyrazolin-5-ones (nitropyrazolones) were proposed as highly active fungicides of the novel structural type. The first scalable and practical method for the nitropyrazolone synthesis was proposed, which is atom-efficient, is applicable for the multigram scale synthesis, and allows for production of a wide variety of nitropyrazolones with high yields and purity. The synthesized compounds demonstrated high fungicidal activity against the broad spectrum of phytopathogenic fungi (

This work explores the level of transparency in reporting the details of computational protocols that is required for practical reproducibility of quantum mechanics/molecular mechanics (QM/MM) simulations. Using the reaction of an essential SARS-CoV-2 enzyme (the main protease) with a covalent inhibitor (carmofur) as a test case of chemical reactions in biomolecules, we carried out QM/MM calculations to determine the structures and energies of the reactants, the product, and the transition state/intermediate using analogous QM/MM models implemented in two software packages, NWChem and Q-Chem. Our main benchmarking goal was to reproduce the key energetics computed with the two packages. Our results indicate that quantitative agreement (within the numerical thresholds used in calculations) is difficult to achieve. We show that rather minor details of QM/MM simulations must be reported in order to ensure the reproducibility of the results and offer suggestions toward developing practical guidelines for reporting the results of biosimulations.

Data for Publication "Molecular Dynamics With DHHC20 Acyltransferase Suggests Principles of Lipid and Protein Substrate Selectivity" Free hDHHC20 enzyme and two of its mutants (S29F and Y181A) describe the protein in the unbound state, prior to the auto- and transacylation reactions. (2) Starting structures of the hDHHC20 and two mutants DHHC20S29F and DHHC20Y181Ain .gro format (without water molecules) in pure POPC bilayer and mixed bilayer, respectively, along with trajectories (dt=1000 ps) in .xtc format: System Starting structure Trajectory Topology DHHC20 in POPC bilayer DHHC20_PC.gro DHHC20_PC.xtc DHHC20.itp DHHC20 in mixed bilayer DHHC20_PIPEPG.gro DHHC20_PIPEPG.xtc DHHC20.itp DHHC20S29F in POPC bilayer DHHC20S29F_PC.gro DHHC20S29F_PC.xtc DHHC20S29F.itp DHHC20S29F in mixed bilayer DHHC20S29F_PIPEPG.gro DHHC20S29F_PIPEPG.xtc DHHC20S29F.itp DHHC20Y181A in POPC bilayer DHHC20Y181A_PC.gro DHHC20Y181A_PC.xtc DHHC20Y181A.itp DHHC20Y181A in mixed bilayer DHHC20Y181A_PIPEPG.gro DHHC20Y181A_PIPEPG.xtc DHHC20Y181A.itp The pre-acylation step, when the substrate analogue has already entered hDHHC’s cavity, but has not yet reacted. DHHC20accommodates acyl-β-mercapto-ethylamine (MEA), an acyl-CoA analogue lacking a large 3’-phosphorylated ADP, within its inner cavity withouta chemical bond formation. (3) Starting structures of the hDHHC20 with substratein .gro format (without water molecules) inmixed bilayer, along with trajectories (dt=1000 ps) in .xtc format: System Starting structure Trajectory Topology DHHC20 with C12-MEA DHHC20_meaC12.gro DHHC20_meaC12.xtc DHHC20.itp, meaC12.itp DHHC20 with C14-MEA DHHC20_meaC14.gro DHHC20_meaC14.xtc DHHC20.itp, meaC14.itp DHHC20 with C16-MEA DHHC20_meaC16.gro DHHC20_meaC16.xtc DHHC20.itp, meaC16.itp DHHC20 with C18-MEA DHHC20_meaC18.gro DHHC20_meaC18.xtc DHHC20.itp, meaC18.itp DHHC20 with C20-MEA DHHC20_meaC20.gro DHHC20_meaC20.xtc DHHC20.itp, meaC20.itp The post-autoacylation step. hDHHC20 topology was modified to form a chemical bond between the cysteine’s sulfur atom and the fatty acid’s Cɑ-atom, which restricts the movement of the fatty acid residue. (4) Starting structures of the acylated hDHHC20.gro format (without water molecules) in mixed bilayer, along with trajectories (dt=1000 ps) in .xtc format: System Starting structure Trajectory Topology DHHC20-C12 DHHC20_C12.gro DHHC20_C12.xtc DHHC20_C12.itp DHHC20-C14 DHHC20_C14.gro DHHC20_C14.xtc DHHC20_C14.itp DHHC20-C16 DHHC20_C16.gro DHHC20_C16.xtc DHHC20_C16.itp DHHC20-C18 DHHC20_C18.gro DHHC20_C18.xtc DHHC20_C18.itp DHHC20-C20 DHHC20_C20.gro DHHC20_C20.xtc DHHC20_C20.itp

To compare the immediate and long-term results of surgical treatment of hemorrhoidal disease (GD) stage II-III using two methods of identification of hemorrhoidal arteries (HA) with their subsequent ligation and mucopexy.A prospective, randomized, controlled, single-center study was conducted to evaluate the effectiveness of HA ligation with and without Doppler navigation. The study included 120 patients: group A - Doppler-guided ligation (GD stage II was found in 27 patients of the group A and 30 patients of the group B (There are no significant advantages of Doppler-guided HA ligation compared to palpation regarding incidence of hemorrhoid prolapse (Сравнение непосредственных и отдаленных результатов хирургического лечения геморроидальной болезни II—III стадии с использованием двух способов идентификации геморроидальных артерий (ГА) с последующим их лигированием и мукопексией.Проведено проспективное, рандомизированное, контролируемое, моноцентровое исследование, оценивающеее эффективность лигирования ГА с применением ультразвуковой доплеровской навигации (УЗДН) и без нее. В исследование включены 120 пациентов: группа А — с использованием УЗДН (В зависимости от стадии геморроидальной болезни (II или III) пациенты распределены следующим образом: со II стадией в группу А вошли 27 пациентов, в группу Б — 30 (Предварительные результаты исследования продемонстрировали отсутствие статистически значимых преимуществ использования ультразвуковой идентификации ГА для их последующего лигирования по сравненио с пальпаторным (дигитальным) определением пульсации ГА как по эффективности устранения пролапса геморроидальных узлов (

S-acylation is a post-translational linkage of long chain fatty acids to cysteines, playing a key role in normal physiology and disease. In human cells, the reaction is catalyzed by a family of 23 membrane DHHC-acyltransferases (carrying an Asp-His-His-Cys catalytic motif) in two stages: (1) acyl-CoA-mediated autoacylation of the enzyme; and (2) further transfer of the acyl chain to a protein substrate. Despite the availability of a 3D-structure of human acyltransferase (hDHHC20), the molecular aspects of lipid selectivity of DHHC-acyltransferases remain unclear. In this paper, using molecular dynamics (MD) simulations, we studied membrane-bound hDHHC20 right before the acylation by C12-, C14-, C16-, C18-, and C20-CoA substrates. We found that: (1) regardless of the chain length, its terminal methyl group always reaches the “ceiling” of the enzyme’s cavity; (2) only for C16, an optimal “reactivity” (assessed by a simple geometric criterion) permits the autoacylation; (3) in MD, some key interactions between an acyl-CoA and a protein differ from those in the reference crystal structure of the C16-CoA-hDHHS20 mutant complex (probably, because this structure corresponds to a non-native dimer). These features of specific recognition of full-size acyl-CoA substrates support our previous hypothesis of “geometric and physicochemical selectivity” derived for simplified acyl-CoA analogues.

Since 2013, neurosurgeons have been guided by the RUANS recommendation protocol for surgical management of patients with acute cervical spine fractures in Russia. However, there are no studies devoted to interobserver agreement between specialists with different experience.To evaluate the role of the RUANS recommendation protocol for decision-making in patients with acute traumatic cervical spine injuries.Twenty-one neurosurgeons from 5 hospitals estimated data of 64 patients with cervical spine fractures. The study implied choosing an option for patient treatment (conservative therapy; anterior, posterior and circular fusion surgery). Two evaluations of CT and MR scans with an interval of 1.5 months were conducted. In the main group (9/21), neurosurgeons strictly followed the RUANS recommendation protocol during re-evaluation. In the control group (12/21), neurosurgeons analysed data considering their own knowledge and experience. Interobserver agreement was evaluated using a Fleiss' or Cohen's Kappa (K).Among the junior neurosurgeons (up to 5 years of experience), change in consent level during re-evaluation was greater in the main group (∆The RUANS recommendation protocol can significantly improve interobserver agreement between specialists with various levels of experience regarding management of acute cervical spine injury.С 2013 г. в России при выборе тактики лечения пострадавших с острыми переломами шейного отдела позвоночника нейрохирург может руководствоваться соответствующим рекомендательным протоколом. Исследований, посвященных уровню согласованности решений, принимаемых на основе рекомендательного протокола специалистами с разным уровнем опыта, нет.Оценить влияние рекомендательного протокола лечения острой осложненной и неосложненной травмы позвоночника у взрослых, предложенного Общероссийской общественной организацией «Ассоциация нейрохирургов России» (Рекомендательный протокол АНР), на уровень согласия специалистов разной квалификации при принятии решения о тактике лечения пострадавших с острой травмой шейного отдела позвоночника.Клинические и радиологические данные 64 пациентов с переломами шейного отдела позвоночника оценены 21 нейрохирургом из 5 стационаров. Следовало выбрать оптимальный вариант лечения (консервативная терапия, передний, задний и циркулярный спондилодез). Все участники оценивали данные 2 раза с интервалом в 1,5 мес. Первую оценку все участники проводили на основании личного опыта. При повторной оценке нейрохирурги основной группы (9 человек) строго следовали Рекомендательному протоколу АНР, участники контрольной группы (12), как и прежде, основывались на собственных знаниях и опыте. Уровень согласия наблюдателей в зависимости от числа участников оценивали при помощи каппы (К) Флейса или Коэна.У хирургов основной группы с опытом работы до 5 лет изменение уровня согласия при повторной оценке было большим (∆Применение рекомендательного протокола лечения острой осложненной и неосложненной травмы позвоночника у взрослых, предложенного Общероссийской общественной организацией «Ассоциация нейрохирургов России», позволяет существенно повысить уровень согласия специалистов разной квалификации при принятии решения о тактике лечения пострадавших с острой травмой шейного отдела позвоночника.

Based on a clinical case, the authors consider the problem of the optimal choice of an antidepressant, taking into account not only the psychopathological structure of depression, the severity and characteristics of its triad, but also the presence of somatic symptoms. This determines the need for a comprehensive analysis of the pharmacological profile of prescribed antidepressants, their psychotropic and somatotropic effects. The switch of the patient to brintellix, which has polymodal neuroreceptor activity, at a dose of 20 mg per day, made it possible to achieve remission and reduce adverse reactions caused by SSRIs.В статье на основе анализа клинического случая рассматривается проблема оптимального выбора антидепрессанта с учетом не только психопатологической структуры депрессии, степени выраженности и особенностей ее триады, но также наличия соматических симптомов. Это определяет необходимость комплексного анализа фармакологического профиля назначаемых антидепрессантов, их психотропных и соматотропных эффектов. Перевод пациента на вортиоксетин (Бринтелликс), обладающий полимодальной нейрорецепторной активностью, в дозе 20 мг в сутки позволил добиться достижения ремиссии и редукции наблюдавшихся на терапии селективными ингибиторами обратного захвата серотонина нежелательных побочных эффектов.

Tk-hefu is an artificial peptide designed based on the α-hairpinin scaffold, which selectively blocks voltage-gated potassium channels K(v)1.3. Here we present its spatial structure resolved by NMR spectroscopy and analyze its interaction with channels using computer modeling. We apply protein surface topography to suggest mutations and increase Tk-hefu affinity to the K(v)1.3 channel isoform. We redesign the functional surface of Tk-hefu to better match the respective surface of the channel pore vestibule. The resulting peptide Tk-hefu-2 retains K(v)1.3 selectivity and displays ∼15 times greater activity compared with Tk-hefu. We verify the mode of Tk-hefu-2 binding to the channel outer vestibule experimentally by site-directed mutagenesis. We argue that scaffold engineering aided by protein surface topography represents a reliable tool for design and optimization of specific ion channel ligands.

The unique properties of the photoswitchable protein Dreiklang are attributed to a reversible hydration/dehydration reaction at the imidazolinone ring of the chromophore. Recovery of the fluorescent state, which is associated with a chemical reaction of the chromophore's dehydration, is an important part of the photocycle of this protein. Here we characterize the fluorescent (ON) and nonfluorescent (OFF) states of Dreiklang and simulate the thermal recovery reaction OFF → ON using computational approaches. By using molecular modeling methods including the quantum mechanics/molecular mechanics (QM/MM) technique, we characterize the structures and spectra of the ON- and OFF-states. The results are consistent with available experimental data. The computed reaction profile explains the observed recovery reaction and clarifies the mechanism of chemical transformations in the chromophore-containing pocket in Dreiklang.

Purpose The aim of this study was to compare the feasibility, safety, and fusion results of posterior transarticular stand-alone screw (SAS) instrumentation of C1–C2 with a minimally invasive technique to those of a posterior midline exposure. Methods Between 2008 and 2016, 164 patients underwent surgical treatment for traumatic injuries to the upper cervical vertebrae at our institution. We included 38 patients (27 men and 11 women; age range, 17–81 years) in the study. The posterior midline approach (PMA) group (23 patients) included patients who underwent surgery by means of a conventional midline incision after percutaneous screw insertion. The transmuscular approach (TMA) group (15 patients) included patients who underwent SAS fixation by use of a minimally invasive technique. The mean follow-up period was 58 months (range, 12–118 months). Results Statistical analysis revealed that the operative time, blood loss volume, and severity of postoperative pain were lower in the TMA group. No significant excess of radiation exposure to the surgical team and the patients occurred in TMA group compared with the PMA group. C1–C2 fusion was observed in 37 patients. Stable fibrous fusion between the C1 and C2 vertebrae was found in 1 patient. Conclusions A minimally invasive technique by use of a paravertebral transmuscular approach provides an alternative to routine posterior transarticular SAS fixation of C1 and C2 through a posterior midline approach. The minimally invasive technique reduces the duration of surgery and the volume of blood loss, decreases the severity of postoperative pain, and does not increase the amount of radiation exposure for the surgical team and the patient.

Objective To perform a radiological analysis of the degeneration of C1-C2 joints after C1-C2 transarticular fixation (TAF) and compare the long-term results of a routine Magerl technique (RMT) to a posterior transarticular C1-C2 stand-alone screw instrumentation (SAS) application. Methods A total of 40 patients (26 men and 14 women) were included in the present retrospective observational cohort study. The mean follow-up period was 61.7 months (range, 11–118). The mean patient age at the baseline examination was 48.4 years (range, 22–82). Of the 40 patients, 11 were included in the RMT group and 29 in the SAS group. Results The structure of 80 atlantoaxial joints was analyzed, with grade 4 degenerative changes observed in 57 joints (71.3%). Of the 40 analyzed atlanto-odontoid joints, grade 4 degenerative changes were revealed in 18 joints (45%). C1-C2 bone fusion was observed in 38 patients (95%) and stable fibrous fusion in 2 patients (5%). No cases of C1-C2 nonunion were revealed. No statistically significant differences in the frequency of C1-C2 fracture consolidation or C1-C2 fusion were revealed between the RMT and SAS groups. Conclusions The application of cortical lag screws in TAF might result in stable atlantoaxial joint fusion formation without joint curettage. Atlanto-odontoid joint fusion was also observed after C1-C2 TAF. The application of cortical lag screws for bilateral fixation using the SAS technique resulted in C1-C2 fusion in 93.1% of cases, comparable to the results with the Magerl technique.

To define the diagnostic power of absolute myocardial blood flow (MBF) evaluation on dynamic CZT imaging in intermediate risk patients in comparison with invasive coronary angiography (ICA) and fractional flow reserve (FFR). Twenty-three stable CAD patients underwent one-day dynamic rest-stress 99mTc-Sestamibi myocardial perfusion imaging by CZT camera. Stress and rest MBF values were calculated semi-automatically using a net retention model by Leppo. Coronary flow reserve (CFR) and flow difference (FD) [MBF stress − MBF rest] were also estimated. A total of 28 vessels were functionally quantified with FFR: 19 (68%) vessels with a stenosis ≥ 70% and 9 (32%) with < 70% stenotic lesions. The mean global MBFs at rest and during stress were 0.36 (IQR 0.33-0.54) mL/min/g and 0.67 (IQR 0.55-0.81) mL/min/g, respectively, with an average CFR of 1.80 (IQR 1.35-2.24). Moderate correlations between stenosis severity and FFR (r = 0.45; P = .01), stress MBF (r = −0.46; P = .01) and FD (r = −0.37; P = .04) were detected. FFR abnormalities were best predicted by absolute stress MBF, CFR and FD with values of ≤ 0.54 mL/min/g (sensitivity 61.5%; specificity 93.3%), ≤ 1.48 (sensitivity 69.2%; specificity 93.3%) and ≤ 0.18 mL/min/g (sensitivity 69.2%; specificity 100%), respectively. The values of stress MBF, CFR and FD obtained through dynamic CZT acquisitions compare well with invasive FFR. The clinical use of dynamic acquisition of myocardial perfusion imaging by CZT may help cardiologist in the detection of hemodynamically significant CAD.

Neonatal severe primary hyperparathyroidism (NSHPT) is a rare autosomal recessive disorder of calcium homeostasis that manifests shortly after birth with hypercalcemia and bone disease. NSHPT, in most cases, is attributed to mutations in the calcium-sensing receptor (CASR) gene. We reprogrammed dermal fibroblasts derived from a patient with NSHPT carrying a compound heterozygous mutation in the CASR gene into induced pluripotent stem cells (iPSCs). The established iPSCs expressed pluripotency markers, maintained normal karyotype and differentiated into all three germ layers. This line is a valuable resource for modeling of hyperparathyroidism related to CASR mutations.

The aim of the study was to evaluate the effectiveness of the global coagulation test of thrombodynamics for monitoring and correcting the hemostatic system and improving the results of complex treatment in patients with SARS-CoV-2 in the COVID hospital. From April 2020 to December 2020 on the basis of the University Clinical Hospital No. 4 of the First Moscow State Medical University named I.M. Sechenov (Sechenov University) of the Ministry of Health of the Russian Federation 245 patients between the ages of 27 and 89 with SARS-CoV-2 associated pneumonia were treated. The mean age of the patients was 56.7 ± 4.2 years. All patients participating in the study were divided by simple randomization into two groups. The volume of lesion of the lung parenchyma was assessed according to the data of computed tomography. All patients were treated for SARS-CoV-2 in a comprehensive manner in accordance with the temporary guidelines of the Ministry of Health of the Russian Federation with the mandatory prescription of low molecular weight heparins (LMWH). Assessment and correction of the hemostasis system in 177 patients (47.7%) of group 1 was carried out daily using local coagulation tests (LCT), including APTT, PT, TT, PTI, INR, Fibrinogen and D-dimer level. The second group included 128 patients (52.3%), who, in addition to local coagulation tests, used the integral coagulation test - the thrombodynamics test- to assess and correct the state of the hemostatic system. Assessment and correction of hemostasis were performed at the control points (1, 7, 14 days) of the study. Compared to LCT, the thrombodynamics test reliably more often revealed the state of hypercoagulability, which was promptly corrected by increased doses of LMWH in group 2. Positive dynamics of clinical symptoms were detected in patients of group 2 1.8 times more often than in group 1 (p0.05): fever and shortness of breath in group 2 decreased faster, the SpO2 index recovered more rapidly, especially in patients with severe hypoxia (with SpO290), the number of patients with moderate and severe severity by the third point of the study in group 2 was 1.8 times less than in group 1 (p0.05). Severe forms of lung damage (CT-3 and CT-4) were detected in group 2 3.2 times less frequently (p0.01) compared with group 1, and the number of deaths was 3.3 times less frequent (p0.01) by the end of the study. The average bed-day in group 2 of patients (15±1.6 days) was 1.6 times shorter than in group 1 (24±7.2 days). Hemorrhagic complications were not recorded, despite the therapeutic doses of LMWH in patients of group 2. The severity of the condition of patients with SARS-CoV-2 and the dynamics of their symptoms depend on the state of microcirculation in the lungs and in the periphery and on the volume of thrombotic lesions. Anticoagulant therapy prescribed as early as possible in adequate therapeutic doses in patients with SARS-CoV-2 associated viral pneumonia made it possible to achieve positive treatment results. The use of the global coagulation thrombodynamics test has shown high efficiency for the timely assessment and correction of the state of the hemostasis system.

The aim of the study was to study the effectiveness of complex treatment of decompensated chronic venous insufficiency (CVI) using innovative techniques and proteolysis inhibitors with a wide spectrum of activity in patients with SARS-CoV-2 (COVID-19) in COVID hospital. This study was performed in the surgical department of COVID hospital on the basis of the Clinical Hospital No. 4 of the First Moscow State Medical University named I.M. Sechenov (Sechenov University). During the period from April 2020 to February 2021, 32 patients with confirmed SARS-CoV-2 (COVID-19) and the presence of venous trophic ulcers (VTU) of the lower extremities were treated. All patients underwent complex therapy for viral pneumonia in accordance with the order of the Ministry of Health of the Russian Federation. The protease inhibitor Aprotinin (Gordox ™) was used to improve microcirculation and prevent the development of a "cytokine storm". To accelerate the cleansing and epithelialization of venous trophic ulcers, the surface of the trophic ulcer was treated with an air plasma flow of NO and injections into the trophic ulcer of autoplasma. Against the background of complex treatment, all patients showed positive dynamics of the clinical picture: relief of hyperthermia, increase or stabilization of SpO2 values from 95% and above, significant decrease in CRP, LDH, D-dimer indices, increase in the number of lymphocytes, decrease in the VTU area by 1.5 times, active granulation and marginal epithelialization of the ulcer. In 14 patients (43.8%), complete epithelialization of the VTU defect was noted by the end of the third week. According to the CIVIQ-20 questionnaire, all 32 patients participating in the study showed positive dynamics. There were no lethal outcomes. Multicomponent therapy of decompensated forms of CVI of the lower extremities in the COVID hospital in patients with moderate severity of coronavirus infection with the use of proteolysis inhibitors leads to a rapid relief of symptoms of intoxication, prevents the progression of lung tissue and parenchymal organ damage and contributes to the positive dynamics of healing of ulcerative defects in the vast majority of patients.

Numerous physiological functions rely on distinguishing temperature through temperature-sensitive transient receptor potential channels (thermo-TRPs). Although the function of thermo-TRPs has been studied extensively, structural determination of their heat- and cold-activated states has remained a challenge. Here, we present cryo-EM structures of the nanodisc-reconstituted wild-type mouse TRPV3 in three distinct conformations: closed, heat-activated sensitized and open states. The heat-induced transformations of TRPV3 are accompanied by changes in the secondary structure of the S2-S3 linker and the N and C termini and represent a conformational wave that links these parts of the protein to a lipid occupying the vanilloid binding site. State-dependent differences in the behavior of bound lipids suggest their active role in thermo-TRP temperature-dependent gating. Our structural data, supported by physiological recordings and molecular dynamics simulations, provide an insight for understanding the molecular mechanism of temperature sensing. Cryo-EM structures of the heat-activated TRP channel TRPV3 in lipid nanodiscs at different temperatures reveal a conformational wave involved in the gating process.

In recent years, the effect of critical conditions on intestine and the role of such changes in maintenance and progression of systemic disorders are of particular attention. This issue is relevant in critically ill neurosurgical patients too. Intestine morphology and microbiome changes in these patients represent a wide field for researches in intensive care and prevention of secondary damage to other organs and systems. This review ensures a current approach to the problem of intestine morphology and microbiome changes in critically ill neurosurgical patients. We reviewed the data from clinical studies and experiments reproducing a critical condition in animals. Most publications are indexed in the PubMed, e-library, Google Scholar databases. We also analyzed the data from NEJM, JAMA, Lancet, Critical Care and other issues. The manuscript contains an overview of 44 foreign and 13 domestic references; over 50% of researches were published within the past 5 years. Searching depth was over 50 years.В последние годы все большее внимание уделяется влиянию критического состояния больного на кишечник и роли возникающих в нем изменений в поддержании и нарастании системных нарушений (так называемой энтеропатии критических состояний). Эта проблема актуальна и при критических состояниях у больных нейрохирургического профиля. Вопрос изменения кишечной морфологии и микробиома у таких пациентов представляет собой широкое поле для исследований в области интенсивной терапии и профилактики вторичного поражения других органов и систем. В обзоре представлены результаты систематического поиска публикаций, посвященных изменению морфологии и микробиоценоза кишечника, главным образом у пациентов с нейрохирургической патологией, а также с данными воспроизведения критического состояния в экспериментальных моделях у животных. Большинство публикаций проиндексированы в базах данных PubMed, e-library, Google Scholar, также использованы данные медицинских изданий NEJM, JAMA, Lancet, Critical Care и других. Статья содержит обзор 44 зарубежных и 13 отечественных источников; более половины работ составляют публикации за последние 5 лет. Глубина поиска составила более 50 лет.

To determine the safe screw trajectory for posterior transarticular fixation of C1–C2 without direct visualisation of C2 lateral masses and by using fluoroscopic landmarks only. Fluoroscopic models of the craniovertebral region in frontal and sagittal planes were reconstructed using 1-mm interval computed tomography scans of the cervical spine in 30 patients. The imitation model of the screw trajectory was then applied with verification of the exact screw localisation using multiplanar reconstruction. Twenty-seven trajectories for 60 oblique C1–C2 reformations were tested. In the frontal plane, all correct trajectories passed through the medial waistline point (WstP) of C3 and through the middle of the lateral mass of C1. In the lateral plane, the posterior spinal process-lateral mass (SpLM) point—middle C1 anterior tuberculum point (ATP), middle SpLM-upper ATP, and lower SpLM-odontoid point (ODP)—had relatively low rates of vertebral artery (VA) injury (2.3%, 4.6%, and 7%, respectively) and other screw malpositions (6.9%, 4.6%, and 4.6%, respectively). In cases of an isthmus height exceeding 8 mm, there were no incidences of VA injury. Patients with an isthmus width greater than 7 mm had a lower risk of screw malposition. We identified potentially safe trajectories for percutaneous posterior transarticular fixation of C1–C2. Using SpLM, ATP, and ODP landmarks in the lateral plane, and WstP and C1 middle landmarks in the frontal plane, it is possible to achieve an acceptable screw position without direct visualisation of the C2 lateral mass.

Here we present the result of our work on achieving sub-pM limit of quantitation in direct quantitative analysis of multiple miRNAs by capillary electophoresis with laser-induced fluorescence detection. The PDF file contains the description of the results with figures, references, and supporting information. The raw data.ZIP file is the archive containing (i) Excel files of raw data used to build figures presented in the PDF file and (ii) the red-me.PDF file explaining how to read and use the Excel files. The figure data.ZIP file is the archive of all figure files in Origin and Adobe Illustrator formats. Abstract: Thousands of putative miRNA-based cancer biomarkers have been reported but none has been validated for approval by the Food and Drug Administration. One of the reasons for this alarming discrepancy is the lack of a method which is sufficiently robust for carrying out validation studies, which may require analysis of samples from hundreds of patients across multiple institutions and pooling the results together. Capillary electrophoresis (CE)-based hybridization assay proved to be more robust than reversed transcription polymerase chain reaction (the current standard) but its limit of quantification (LOQ) exceeds 10 pM while miRNA concentrations in cell lysates are below 1 pM. Thus, CE-based separation must be preceded by on-column sample preconcentration. Here we explain challenges of sample preconcentration for CE-based miRNA analyses and introduce a preconcentration method that can suit CE-based miRNA analysis utilizing peptide nucleic acid (PNA) hybridization probes. The method combines field-amplified sample stacking (FASS) with isotachophoresis (ITP). We proved that FASS-ITP could retain and concentrate both near-neutral PNA with highly-negatively charged PNA–miRNA hybrids. We demonstrated that preconcentration by FASS-ITP could be combined with the CE-based separation of the unreacted PNA probes from the PNA–miRNA hybrids and facilitate improvement in LOQ by a factor of 140, down to 0.1 pM. Finally, we applied FASS-ITP-CE for simultaneous detection of two miRNAs in crude cell lysates and proved that the method was robust when used in complex biological matrices. The 140-fold improvement in LOQ and the robustness to biological matrices will significantly expand the applicability of CE-based miRNA analysis, bringing it closer to becoming a practical tool for validation of miRNA biomarkers.

Patients in chronic critical illness after brain injury may experience various conditions that limit nutritional support.

To compare different clinical and morphometric features of patients undergoing TPAIT for prediction of postoperative outcomes.A retrospective review enrolled patients who underwent TPAIT for the period from January 2007 to October 2017. Morphometric parameters were analyzed using preoperative CT scans and patients were grouped to examine association of these characteristics with postoperative morbidity. Sarcopenia was defined as the presence of a TPA in the lowest sex-specific quartile. The impact of sarcopenia on pancreatic islet features, perioperative blood transfusion, ICU- and hospital-stay, complications, repeated admission within 90 days and islet function was assessed.A total of 34 patients were included in this study (12 males and 24 females). At the time of diagnosis, mean age of patients was 43.1 years. Mean body mass index (BMI) in sarcopenic patients was 24.9 kg/mSarcopenia is not a predictor of postoperative complications and islet cell function in chronic pancreatitis patients following TPAIT.Тотальная панкреатэктомия сопровождается высокой заболеваемостью и летальностью. Точные критерии, которые могли бы прогнозировать исход после этой операции с последующей аутотрансплантацией островковых клеток (TPAIT), в настоящее время отсутствуют.Сравнение различных клинико-морфометрических особенностей пациентов, перенесших TPAIT, для прогнозирования исходов хирургического вмешательства.В ретроспективный обзор включили истории болезни пациентов, перенесших TPAIT в период с января 2007 г. по октябрь 2017 г. До операции измеряли морфометрические параметры жировой клетчатки по сканам компьютерной томографии. Пациентов сгруппировали так, чтобы изучить связь этих показателей с послеоперационной заболеваемостью. Саркопению определяли как наличие патологической потери жировой прослойки и мышечной массы и объективизировали расчетом площади сечения поясничной мышцы в последнем зависимом от пола квартиле. Оценивали влияние саркопении на характеристики островков поджелудочной железы, интраоперационное переливание крови, сроки пребывания в отделении интенсивной терапии и госпитализации, частоту развития послеоперационных осложнений, повторного поступления в 90-дневный период после операции и функцию островков.В исследование включили 34 пациента (12 мужчин и 24 женщины), средний возраст больных — 43,1 года. Индекс массы тела у пациентов с саркопенией в среднем составил 24,9 кг/мРезультаты исследования показали, что саркопения не является предиктором послеоперационных осложнений и функционирования островковых клеток у больных хроническим панкреатитом, перенесших TPAIT.

As shown in our previous paper ('Regression I. Experimental approaches to regression', JAP, 65, 2, 345-65), the common mechanism of regression can be described as reversible dedifferentiation, which is understood as a relative increase of the proportion of low-differentiated (older) systems in actualized experience. Experimental data show that regression following disease (chronic tension headache) is followed by adaptation and an increase in system differentiation in that experience domain which contains systems responsible for that adaptation. The results of mathematical modelling support the idea that reversible dedifferentiation can be one of the mechanisms for increasing the effectiveness of adaptation through learning. Reversible dedifferentiation, which is phenomenologically described as regression, is a general mechanism for restructuring the organism-environment interactions in situations where behaviours that were effective in the past become ineffective. Reversible dedifferentiation has evolved as a component of adaptation when new behaviours are formed and large-scale modifications in the existing behaviours are required in the face of changes in the external and/or internal environment. Thus, the authors believe that this article provides evidence for Jung's view that regression is not only a 'return' to past forms of thinking, affects and behaviour, but that regressive processes provide a significant impetus for psychological growth and development.Comme nous l’avons montré dans notre article précédent (« Régression I. Les approches expérimentales de la régression »), le mécanisme propre à la régression peut être décrit en tant que dé-différentiation réversible, ce que l’on peut comprendre comme une hausse relative de la proportion de systèmes peu différentiés (plus vieux) dans l’expérience actualisée. Les données expérimentales montrent que la régression suite à une maladie (mal de tête de tension chronique) est suivie par une adaptation et un accroissement dans la différentiation des systèmes dans le domaine d’expérience qui contient les systèmes responsables de cette adaptation. Les résultats de la modélisation mathématique soutiennent l’idée que la dé-différentiation réversible peut être l’un des mécanismes pour accroitre l’efficacité de l’adaptation par l’apprentissage. La dé-différentiation réversible, qui est décrite phénoménologiquement comme régression, est un mécanisme général pour restructurer les interactions organisme-environnement dans des situations où les comportements qui fonctionnaient par le passé sont devenus inefficaces. La dé-différentiation réversible a évolué comme un élément de l’adaptation quand de nouveaux comportements se développent et que des changements dans l’environnement extérieur ou intérieur requièrent des modifications à grande échelle dans les comportements existants. Ainsi, les auteurs pensent que cet article apporte un soutien à la perspective de Jung selon laquelle la régression n’est pas seulement un « retour » à des formes anciennes de fonctionnement, d’affects et de comportement, mais que les processus régressifs fournissent un élan significatif pour la croissance et le développement psychologiques.Wie wir in unserem vorangegangenen Artikel gezeigt haben (‘Regression I. Experimentelle Ansätze zur Regression’), kann der gewöhnliche Regressionsmechanismus als reversible Entdifferenzierung beschrieben werden, die als relative Zunahme des Anteils niedrig differenzierter (älterer) Systeme innerhalb aktualisierten Erlebens verstanden wird. Experimentelle Daten zeigen, daß auf die nach einer Krankheit (chronischer Spannungskopfschmerz) auftretende Regression eine Anpassung und eine Zunahme der Systemdifferenzierung in jenem Erfahrungsbereich folgt, der Systeme enthält, die für diese Anpassung verantwortlich sind. Die mit Hilfe eines mathematischen Modells gewonnenen Ergebnisse stützen die Idee, daß reversible Entdifferenzierung einer der Mechanismen zur Steigerung der Wirksamkeit der Anpassung durch Lernen sein kann. Reversible Entdifferenzierung, die phänomenologisch als Regression bezeichnet wird, ist ein allgemeiner Mechanismus zur Restrukturierung der Wechselwirkungen zwischen Organismus und Umwelt in Situationen, in denen Verhaltensweisen, die in der Vergangenheit wirksam waren, unwirksam werden. Reversible Entdifferenzierung hat sich als Bestandteil der Anpassung entwickelt, wenn neue Verhaltensweisen gebildet werden und umfangreiche Änderungen an den vorhandenen Verhaltensweisen angesichts von Änderungen in der externen und/oder internen Umgebung erforderlich sind. Die Autoren gehen daher davon aus, daß dieser Artikel die Ansicht von Jung belegt, daß Regression nicht nur eine 'Rückkehr' zu früheren Formen des Denkens, von Affekten und Verhalten ist, sondern daß regressive Prozesse einen signifikanten Impuls für psychologisches Wachstum und Entwicklung liefern.Come abbiamo mostrato nel nostro precedente articolo ('Regressione I. Approcci sperimentali alla regressione'), il comune meccanismo di regressione può essere descritto come una de-differenziazione reversibile, che è intesa come un aumento dei sistemi poco differenziati (vecchi) nell'esperienza concreta. I dati sperimentali mostrano che la regressione successiva ad un disturbo (come il mal di testa da tensione cronica) è seguita dall'adattamento e da un aumento della differenziazione del sistema in quel settore di esperienza che contiene i sistemi responsabili di tale adattamento. I risultati della modellazione matematica supportano l'idea che la de-differenziazione reversibile possa essere uno dei meccanismi che aumentano l'efficacia dell'adattamento attraverso l'apprendimento. La de-differenziazione reversibile, che è fenomenologicamente descritta come regressione, è un meccanismo generale per la riorganizzazione delle interazioni organismo-ambiente in situazioni in cui comportamenti che erano efficaci in passato diventano inefficaci. La de-differenziazione reversibile si è evoluta in una componente dell’adattamento rispetto a nuovi comportamenti o modifiche su larga scala nei comportamenti esistenti, a fronte di cambiamenti nell'ambiente esterno e/o interno. Pertanto, gli Autori ritengono che questo articolo offra sostegno all’idea di Jung secondo cui la regressione non è solo un “ritorno” a forme passate di pensiero, affetti e comportamento, ma fornisca anche un impulso significativo per la crescita e lo sviluppo psicologico.Как мы показали в нашей предыдущей статье («Регрессия I. Экспериментальные подходы к регрессии»), общий механизм регрессии можно описать как обратимую дедифференциацию, которая понимается как относительное увеличение доли низкодифференцированных (более старых) систем в актуализированном опыте. Экспериментальные данные показывают, что возникающая после заболевания (например, после хронической головной боли напряжения) регрессия сопровождается адаптацией и увеличением системной дифференциации в то м домене опыта, которыйсодержит системы, ответственные за эту адаптацию. Результаты математического моделирования подтверждают идею о том, что обратимая дедифференциация может быть одним из механизмов повышения эффективности адаптации посредством обучения. Обратимая дедифференциация, которая феноменологически описывается как регрессия, является общим механизмом реструктуризации взаимодействий организм-среда в ситуациях, когда поведение, которое было эффективным в прошлом, становится неэффективным. Обратимая дедифференциация развивается как компонент адаптации, когда формируется новое поведение и требуются крупномасштабные изменения в существующем поведении перед лицом изменений во внешней и/или внутренней среде. Таким образом, авторы полагают, что в этой статье подтверждается мнение Юнга о том, что регрессия - это не только «возврат» к прошлым формам мышления, аффектов и поведения, но и то, что регрессивные процессы дают значительный импульс для психологического роста и развития.Como hemos mostrado en nuestros trabajos previos (‘Regresión I. Abordajes experimentales hacia la regresión’), el mecanismo común de la regresión puede ser descripto como desdiferenciación reversible, el cual es comprendido como un relativo incremento en la proporción de sistemas de baja-diferenciación en la experiencia actual. Data experimental muestra que la regresión luego de una enfermedad (tensión de cabeza crónica) es seguida por la adaptación y por un incremento en la diferenciación de sistemas en aquel dominio de la experiencia, que contiene sistemas responsables para tal adaptación. Los resultados del modelo matemático sostienen la idea de que la desdiferenciación reversible puede ser uno de los mecanismos para incrementar la efectividad de la adaptación a través del aprendizaje. La desdiferenciación reversible, la cual fenomenológicamente se describe como regresión, es un mecanismo general para restructurar las interacciones entre el organismo y el medio ambiente, en situaciones en las que las conductas que eran efectivas en el pasado se vuelven ineficaces. La desdiferenciación reversible ha evolucionado como un componente de la adaptación cuando se forman nuevas conductas y se requieren modificaciones a gran escala en las conductas existentes frente a los cambios en el medio ambiente externo y/o interno. Así, los autores consideran que el artículo proporciona evidencia a la perspectiva de Jung sobre la regresión, no solamente como un ‘retorno’ a formas de pensar, sentir y actuar del pasado sino que los procesos regresivos proveen un estímulo significativo para el desarrollo y el crecimiento psicológico.退行II:通过退行得以发展 在第一篇文章中 (退行I:退行的实证取向), 退行的一般机制可以被描述为一种可逆的去分化, 这可以理解为, 低分化的 (旧的)系统在实际经验中所占比例的相对增长。实验数据显示, 与退行相随的疾病 (慢性紧张性头痛)之后, 会发生适应, 以及系统分化的增长, 因为这一经验领域包含了作用于适应的系统。数学建模的研究结果也支持这一观念, 即可逆的去分化是一种通过学习来增进适应效率的机制。可逆的去分化在现象学上被描述为退行, 它是一种普遍的机制, 用以重建有机环境中的互动, 在这些情境中, 以往有效的行为开始失效。当新的行为形成, 个体为了面对内外环境的变化, 对已有行为进行必要的大尺度调整时, 可逆的去分化便进化为适应的一个组成部分。于是, 作者相信这篇文章为荣格的退行观点提供了支持, 即退行不仅仅是“回归”过往的思维方式、情感和行为, 而是说, 退行还为心理成长与发展提供了重要的动力。.

The aim of the study - to identify the causes and develop methods of treatment and prevention of septic phlegmons of the lower extremities after combined phlebectomy. The article presents the experience of treating 6 patients between the ages of 21 and 69 years with severe pyo-inflammatory complications (septic phlegmons) of the lower extremities after combined phlebectomy between 2012 and 2019. All patients had signs of a expressed systemic inflammatory response (SIRS3 and SIRS4) when they received admission. Against the background of intensive detoxification therapy in intensive care department, all patients were operated on emergency indications. Under anesthesia, they were performed an opening the subcutaneous phlegmons of the lower extremities using wide stripes incisions. Comprehensive therapy included the prescribing of antibiotics, anti-inflammatory drugs, stage necrectomy, the treatment of purulent wounds with various variants of surgical energy (plasma flows and NO-therapy) in various modes. The results of the treatment were estimated in the near and distant periods. Timely diagnosis, surgical treatment with the opening of purulent cavities with a wide excision of necrotized subcutaneous fat and fascia, as well as the subsequent plasmadynamic stage wound purification in therapeutic mode allowed in all cases to stop systemic inflammatory syndrome, to achieve rapid cleansing and healing of wounds. All patients were discharged for outpatient treatment. There were no fatalities. The long-term results of treatment were found to be satisfactory, and no patients were found to be disabled. The careful compliance to the main stages of the combined phlebectomy, especially the quality control of postoperative hemostasis, can minimize the development of septic complications. The comprehensive treatment with active surgical tactics and the use of air-plasma technologies allow to achieve a rapid cleansing of wounds and a speedy recovery of patients.

The primary goal of this study was to conduct a systematic review and meta-analysis of articles focused on odontoid screw fixation (OSF) and screw-related complications or non-union rates.We conducted a systematic review of the PubMed and Crossref databases between January 1982 and December 2019. Inclusion criteria comprised detailed descriptions of the surgical technique and screw-related complications (screw cut-out, loosening, breakage, malposition) or fusion rates.The initial selection consisted of 683 abstracts. A total of 150 full texts were chosen for detailed study, and 83 articles were included in the analysis. The point estimates for screw-related complications were as follows: 1. screw malposition frequency-4.8%; 2. screw cut-out rate-5.0%; 3. screw loosening/pull-out-3.8%; and 4. screw fracture rate-3.1%. The point estimate for the non-union rate was 9.7%. Statistical analysis of the screw-related complications rate based on surgical technique details was also performed CONCLUSIONS: Double-screw OSF performance in elder patients resulted in a higher risk of post-operative screw cut-out. In other cases, the development of screw-related complications did not depend on the method of intraoperative head fixation, selection of the implant entry point for OSF, type of the used screws, or cannulated instruments application. The outcomes of single-screw fixation through the anterior lip of the C2 vertebra were comparable to other techniques of OSF. Further, statistically reliable studies should be carried out to identify the optimal technique of OSF.

To evaluate the results of surgical treatment of patients with unilateral MRI-positive temporal forms of drug-resistant epilepsy.A prospective analysis of 50 patients with unilateral MRI-positive temporal forms of drug-resistant epilepsy, who had undergone resective surgery in the Scientific Research Institute of Emergency Medicine of N.V. Sklifosovsky (Moscow) and in University Clinic of Moscow State University of Medicine and Dentistry between 01.01.14 and 12.12.17, has been performed. MRI-positive temporal symptomatic epilepsy was identified in 79 (55%) patients. MRI results showed unilateral temporal epileptogenic lesions in 50 (67%) patients. These patients were assigned to medial frontal lobectomy.82% patients become 'seizure free' 12 and 24 months after surgical treatment. In other cases, seizures become less frequent and severe.The results confirm the efficacy and safety of surgical treatment of drug-resistant MRI-positive temporal forms of epilepsy.Цель исследования. Оценка результатов хирургического лечения пациентов с фармакорезистентными МРТ-позитивными височными формами симптоматической эпилепсии. Материал и методы. Обследовали 145 пациентов с фармакорезистентными формами симптоматической эпилепсии. Височная МРТ-позитивная форма симптоматической эпилепсии была выявлена у 79 (55%) пациентов. Из них у 50 (67%) по данным МРТ головного мозга были обнаружены односторонние височные эпилептогенные поражения. Этим пациентам была проведена передняя медиальная лобэктомия. Результаты и заключение. У 82% больных после хирургического лечения через 12 и 24 мес приступы стали контролируемыми или отсутствовали. У остальных пациентов приступы стали менее тяжелыми и частыми. Получены данные, подтверждающие эффективность и безопасность хирургического лечения фармакорезистентных МРТ-позитивных височных форм симптоматической эпилепсии.

Methodologies to identify epitopes or ligands of the fungal cell wall polysaccharides influencing the immune response of human pathogens have to date been imperfect. Using the galactomannan (GM) of Aspergillus fumigatus as a model, we have shown that synthetic oligosaccharides of distinct structures representing key fragments of cell wall polysaccharides are the most precise tools to study the serological and immunomodulatory properties of a fungal polysaccharide.

This study aimed to evaluate the impact of several factors, including patients’ intraoperative position, intraoperative visualization technique, fixation method, and type of screws and their parameters, on the frequency of intraoperative screw-associated complications in posterior transarticular C1–C2 fixation. A systematic review of the PubMed database between January 1986 and March 2018 was performed. The key inclusion criteria comprised detailed descriptions of the surgical technique and post-operative screw-associated complications. The initial search resulted in 1041 abstracts, and a total of 54 abstracts were included in the present study. The overall number of operated patients was 2306. In this group, 4439 screws were inserted. The rate of screw-associated complications during the different time periods was estimated upon meta-analysis. Statistical analysis of the screw malposition rate, vertebral artery injury rate, screw breakage rate based on patients’ intraoperative position, intraoperative visualization technique, fixation method, and type of implants and their parameters was also performed. The factors that help reduce the rate of screw-associated complications include the intraoperative application of biplanar fluoroscopy or neuronavigation system, the use of 4 mm or thicker lag screws, and screw insertion through contraincisions using cannulated ported instruments. On the other hand, the potential risk factors of screw-associated complications include inadequate intraoperative head fixation using skeletal traction, uniplanar fluoroscopy-guided screw insertion, screw insertion using the posterior midline approach, and the use of 3.5 mm or thinner full-threaded screws. These slides can be retrieved under Electronic Supplementary Material.

Background Kimmerle anomaly is characterized by ossification of the posterior atlanto-occipital membrane with formation of a complete or incomplete bony ridge in the area of the groove for the vertebral artery (VA) (ponticulus posticus [PP]). In some cases, the bony ridge may also be formed at the level of the VA emerging from the transverse process of the С1 vertebra (ponticulus lateralis [PL]). Simultaneous 1-sided formation of PL and PP is very rare. Data concerning surgical treatment for compression of the VA owing to PL are lacking. Case Description A 34-year-old woman presented with significant dizziness to the point of losing consciousness while rotating her head to the left. Computed tomography angiography of the cervical spine revealed С1 anomaly with the formation of PP and PL with acute-angled С-shaped kinking of the VA. The patient underwent resection of the bony ridges through minimally invasive lateral (PP) and far-lateral (PL) approaches. Treatment led to significant improvement in quality of life, with disappearance of the pain syndrome via the С1 spinal root and absence of bow hunter's syndrome in the postoperative period. Conclusions This is the first report to our knowledge on the surgical treatment of VA compression owing to PP and PL. VA decompression in such cases can be performed via 2 separate minimally invasive lateral and far-lateral approaches. Surgical strategies for treatment of Kimmerle anomaly may significantly improve patients' quality of life.

Bacteriophage particles are the most abundant biological entities on our planet, infecting specific bacterial hosts in every known environment and being major drivers of bacterial adaptive evolution. The study of bacteriophage particles potentially sheds light on the development of new biotechnology products. Bacteriophage therapy, although not new, makes use of strictly lytic phage particles as an alternative in the antimicrobial treatment of resistant bacterial infections and is being rediscovered as a safe method due to the fact that these biological entities devoid of any metabolic machinery do not have affinity to eukaryotic cells. Furthermore, bacteriophage-based vaccination is emerging as one of the most promising preventive strategies. This review paper discusses the biological nature of bacteriophage particles, their mode(s) of action and potential exploitation in modern biotechnology. Topics covered in detail include the potential of bacteriophage particles in human infections (bacteriophage therapy), nanocages for gene delivery, food biopreservation and safety, biocontrol of plant pathogens, phage display, bacterial biosensing devices, vaccines and vaccine carriers, biofilm and bacterial growth control, surface disinfection, corrosion control, together with structural and functional stabilization issues., Project funding by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, São Paulo, Brazil) (FAPESP Refs. No. 2016/08884- 3 (Project PneumoPhageColor) and 2016/12234-4 (Project TransAppIL)), is hereby gratefully acknowledged. Funding by Fundação de Amparo à Pesquisa do Estado de São Paulo(FAPESP Ref. No. 2016/ 16641-3) in the form of an M.Sc. fellowship granted to Liliam Harada is hereby gratefully acknowledged. This work also received support from CNPq, National Council for Scientific and Technological Development Brazil, in the form of Research Productivity (PQ) fellowships granted to Victor M. Balcão (Refs. No. 306113/2014-7 and 308208/2017-0). Financial support to Krystyna Dąbrowska by the National Science Centre in Poland (Grant UMO-2012/05/E/NZ6/03314) is also gratefully acknowledged. The authors have no conflicts of interest whatsoever to declare., info:eu-repo/semantics/publishedVersion

Novel fluorogenic dyes based on the GFP chromophore are developed. The compounds contain a pyridinium ring instead of phenolate and feature large Stokes shifts and solvent-dependent variations in the fluorescence quantum yield. Electronic structure calculations explain the trends in solvatochromic behavior in terms of the increase of the dipole moment upon excited-state relaxation in polar solvents associated with the changes in bonding pattern in the excited state. A unique combination of such optical characteristics and lipophilic properties enables using one of the new dyes for imaging the membrane structure of endoplasmic reticulum. An extremely high photostability (due to a dynamic exchange between the free and absorbed states) and selectivity make this compound a promising label for this type of cellular organelles.

To conduct a systematic review and meta-analysis to determine the frequency of Kimmerle's anomaly (KA) in patients with grades III and IV vertebral artery (VA) sulcus ossification.We searched the PubMed and eLIBRARY.RU databases, identified 68 articles in English, and obtained data of 29.770 patients. To date, no study in Russia has reported KA. The incidence of KA was determined using single-group meta-analysis. We used odds ratios (OR) to investigate the association between sex and the frequency of KA. Publication bias was assessed using the Egger test.The pooled prevalence of complete KA was 8.6% (95%, confidence interval (CI) 7.8-9.5%); however, the Egger test confirmed publication bias (The incidence of KA was significantly associated with the macroregion. Nearly 15.8% of the population may show grades III and IV VA sulcus ossification, and surgical treatment is required in some patients. KA formation is more typical for males. A population study is warranted to clarify the frequency of KA in the Russian population.Проведены систематизированный обзор и метаанализ литературы для определения частоты формирования у лиц с аномалией Киммерле с III и IV степенями оссификации борозды позвоночной артерии.Проведен поиск статей в базах данных PubMed и eLIBRARY.RU. В 68 англоязычных статьях были исследованы данные 29 770 человек. В России популяционные исследования встречаемости аномалии Киммерле не проводились. Частота формирования аномалии Киммерле была определена при помощи одногруппового метаанализа. Взаимосвязь пола и частоты формирования аномалии Киммерле исследовали при помощи отношения шансов (ОШ). Публикационное смещение оценивали при помощи теста Эггера.Совокупная частота встречаемости полной аномалии Киммерле составила 8,6% (95% доверительный интервал (ДИ) 7,8—9,5%), однако при тесте Эггера было подтверждено публикационное смещение (Совокупная частота встречаемости аномалии Киммерле существенно зависит от региона проживания. В целом до 15,8% населения могут иметь III и IV степени оссификации борозды позвоночной артерии, которые при определенных условиях могут потребовать хирургического лечения. Формирование аномалии Киммерле более характерно для лиц мужского пола. Популяционное исследование должно быть проведено в России для уточнения частоты встречаемости III и IV степеней оссификации борозды позвоночной артерии при аномалии Киммерле среди населения.

Evaluate antibacterial activity of an experimental mixture of phages, belonging to several well-studied species.The study was carried out using a group of 55 clinical Pseudomonas aeruginosa strains of various origins,- 4 mono-species mixtures of 32 virulent bacteriophages (species phiKZ-, phiKMV-, phiPBl-, PaP3-like phages) and 2 novel phages, phiMK (species PaK-P2) and phiPerm5. Activity of preparations from mono-species mixtures of bacteriophages ofvarious species were compared with activity of 3 commercial mixtures. Standard methods of study of bacteriophages were used: determination of lytic activity by seeding onto bacterial lawns of P. aeruginosa, restriction analysis of phage DNA for confirmation of their be- longing to certain species.Cumulative activity of 6 mono-species mixtures of virulent phages was shown to be similar to lytic activity of commercial therapeutic mixtures used against P. aeruginosa infections. 54 of 55 strains of clinical isolates of P: aeruginosa showed sensitivity to experimental mixtures composed of mono-species mixtures of bacteriophages. 53 strains were lysed by commercial preparations. Wherein the possibility of accidental inclusion of moderate -bacteriophages in the experimental mixture is excluded.A possibility of creation of highly active therapeutic antibacterial preparations against P. aeruginosa using mono-species mixtures of 6 species of lytic bacteriophages is shown Use of such a mixture in therapy of lung infections reduces the risk of emergence of bacterial strains with increased virulence and patho- genicity during prolonged administration.

Objective: to examine relationship between anatomical changes of the left ventricle (LV), dynamics of velocity of its volume modification, and blood flows in the LV in patients with mitral regurgitation (MR) before and after surgical treatment. Materials and methods. We included into this study 58 patients with severe 3-4 degree MR (38 men, 20 women aged 24-69 [mean age 51±9] years) in sinus rhythm (96%) or atrial fibrillation (4%). The control group included 86 healthy volunteers, mean age 39±7 years. Transthoracic echocardiographic studies were performed in both groups by standard technique at rest using a high-quality echocardiograph Vivid E9, equipped with a 3.5-4.6 MHz multi frequency transducer (in patients before and after surgical repair - mitral valve [MV] replacement and MV reconstruction with annuloplasty ring). The analysis of files recorded was performed off-line by vector analysis technique including estimation of myocardial deformation velocities and dynamics of LV volume modification, construction of “flow-volume” diagram, calculation of the expended kinetic energy, and registration of intraventricular blood flows. Results. End diastolic volume (EDV), end systolic volume (ESV) and total stroke volume (TSV) (effective + retrograde) were significantly increased in patients with severe LV volume overload before surgery in comparison with the control group (p kin ) in patients with MR before surgery was several times higher in diastole than in systole. After MV replacement E kin in systole and diastole decreased becoming closer to normal values. MV replacement restored the pattern of LV filling from the left atrium, and the blood flow reached the LV apex virtually without energy loss. Conclusions. Thus, myocardial deformation velocities, LV blood flows allow to quantify cardiac function in patients with MV insufficiency and to assess the effectiveness of surgical treatment in the early and remote postoperative periods. Phenomenological patterns in evaluation of LV myocardial function and valve apparatus are based not only on anatomical changes of heart chambers, but also on the dynamics of myocardial deformation velocities, what allows to get closer to a assessment of global cardiac function, taking into consideration blood flow dynamics and turbulence in the ventricles, characterizing the cardiac performance and particularly the kinetic energy of the myocardium. Evaluation of stagnant areas in the LV based on the velocity of intracardiac blood flow, reconstructed from color Doppler mapping can be used as a method to identify topological structures with the assessment of qualitative and quantitative characteristics of the myocardium and valve apparatus.

Treatment and prevention of infectious complications remain the actual problems of surgery. Purulent complications very often arise in operative interventions with an application of various fixing devices. A study of the adhesive surgical antiseptic (ASA) «ARGAKOL» (Registration certificate № FS 012б2005/1878-05) was completed. The results of the preliminary antimicrobial activity of the developed composition showed that ASA «ARGAKOL» had a broad spectrum of antimicrobial action. There was used the method of twofold serial dilutions in a liquid medium and Cup-suspension. The study of the influence of the ASA «ARGAKOL» on the wound healing was made in the experiment on white outbred rats. There were carried out two series of experiments with 10 rats in each group: on the model of just contaminated wound (the first series) and on the model of infected wound with delayed application of the glue (after 3 days) after trauma (the second series).

Analysis of proteinogenic vaccine antigens in a quality control environment requires an accurate, precise, and reliable method for protein separation and quantitation. While having multiple advantages over the classical SDS-PAGE, capillary gel electrophoresis (CGE) has not yet become a standard tool in vaccine antigen analysis. Here we report on development of a CGE-based method for quantitative analysis of a tuberculosis vaccine fusion antigen protein, H4, currently in clinical trials. We demonstrate that our method can monitor antigen purity and relative quantity with greater precision and accuracy versus SDS-PAGE. In addition, due to use of direct light-absorbance detection, the CGE method is suitable for absolute quantitation, an application for which SDS-PAGE is limited due to the need for staining and limited dynamic range of detection. To further improve the performance of our quantitation method, we introduced Bovine Serum Albumin (BSA) as an injection standard to correct for signal variance associated with the injected sample volume. We found that, for our specific application, BSA was more appropriate as an injection standard versus one provided in a commercial kit, in terms of precision and accuracy for quantitation of H4. In addition to providing better method performance versus SDS-PAGE, CGE is also faster and less resource-intensive. We conclude that CGE should be considered as a replacement for traditional SDS-PAGE methods for vaccine antigen quantitation in a quality-control environment.

This study set out to investigate chromosomal damage in peripheral blood lymphocytes of thyroid cancer patients receiving 131I for thyroid remnant ablation or treatment of metastatic disease. The observed chromosomal damage was further converted to the estimates of whole-body dose to project the adverse side effects. Chromosomal aberration analysis was performed in 24 patients treated for the first time or after multiple courses. Blood samples were collected before treatment and 3 or 4 days after administration of 2–4 GBq of 131I. Both conventional cytogenetic and chromosome 2, 4 and 12 painting assays were used. To account for dose-rate effect, a dose-protraction factor was applied to calculate the whole-body dose. The mean dose was 0.62 Gy (95% CI: 0.44–0.77 Gy) in the subgroup of patients treated one time and 0.67 Gy (95% CI: 0.03–1.00 Gy) in re-treated patients. These dose estimates are about 1.7-fold higher than those disregarding the effect of exposure duration. In re-treated patients, the neglected dose-rate effect can result in underestimation of the cumulative whole-body dose by the factor ranging from 2.6 to 6.8. Elevated frequency of chromosomal aberrations observed in re-treated patients before radioiodine therapy allows estimation of a cumulative dose received from all previous treatments.

To examine the association of signal transducer and activator transcription 4 (STAT4) rs7574865 G/T polymorphism with a predisposition to systemic sclerosis (SSC) and associated clinical and autoimmune phenotypes in a Russian population.A total of 102 patients with SSC and 103 healthy individuals as controls were examined. STAT4 rs7574865 polymorphism was investigated by real-time polymerase chain reaction.The carriers of the T allele showed a statistically significant association with SSC, a diffuse form (DF), the presence of interstitial lung disease (ILD), cardiac injury (CI), and seropositivity for anti-topoisomerase I antibodies (ATA).The findings results confirm the important role of STAT4 gene in the predisposition to SSC and its phenotypes, such as DF, ILD, CI, and ATA in the Russian population.Цель исследования. Изучение ассоциации полиморфизма rs7574865 (G/T) гена сигнального трансдуктора и активатора транскрипции 4-го типа (STAT4) с предрасположенностью к системной склеродермии (ССД) и ассоциированных с ним клинических и аутоиммунных фенотипов в русской популяции. Материалы и методы. Обследовали 102 пациента с ССД и 103 здоровых лиц в качестве контроля. Полиморфизм rs7574865 гена STAT4 исследовали с помощью полимеразной цепной реакции в реальном времени. Результаты. Показано, что у носителей аллеля Т имеется статистически значимая ассоциация с ССД, диффузной формой (ДФ), наличием интерстициального поражения легких (ИПЛ), поражения сердца (ПС) и серопозитивностью по антителам к топоизомеразе I (АТА). Заключение. Полученные результаты подтверждают важную роль гена STAT4 в предрасположенности к ССД и ее фенотипам: ДФ, ИПЛ, ПС и АТА в русской популяции.

A new sensitive non-invasive gold nanoparticle-based sensor that enables to detect thiols in the human skin has been developed. The detection procedure implied the assessment of the color change of a paper sensor resulting from aggregation of gold nanoparticles caused by thiols. The ratio of the intensity of the photo image blue channel vs the red one (in units of RGB coloration) served as analytical response. The main thiol in the skin is glutathione, therefore, it was used as model biothiol and spiking substance. The range of linearity for glutathione was 8–75 µM, the detection limit was 6.9 µM. RSD≤7% is for inter-day determination of 10 μM glutathione and RSD≤12% is the intra-day value. The recovery of 5 µM and 10 µM of glutathione was evaluated by applying solution, containing thiol-spikes, on skin. The results varied in the range 77–138%. A hundred-fold excess of serine, alanine, histidine, threonine, creatinine, urea, and ammonia; a ten-fold excess of glycine, proline, leucine, isoleucine, phenylalanine, asparagine; and a five-fold excess of valine, tryptophan, tyrosine, and uric acid, which can be extracted from the skin and is contained in the test matrix, have no significant effect on 10 µM glutathione signal. Thiols level in the skin of volunteers (21–65 years old, men and women) detected with the use of a proposed non-invasive sensor was 11.6–47.5 µM.