Репозиторий Университета

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Anorexia nervosa (AN) is an eating disorder often occurring in adolescence. AN has one of the highest mortality rates amongst psychiatric illnesses and is associated with medical complications and high risk for psychiatric comorbidities, persisting after treatment. Remission rates range from 23% to 33%. Moreover, weight recovery does not necessarily reflect cognitive recovery. This issue is of particular interest in adolescence, characterized by progressive changes in brain structure and functional circuitries, and fast cognitive development. We reviewed existing literature on fMRI studies in adolescents diagnosed with AN, following PRISMA guidelines. Eligible studies had to: (1) be written in English; (2) include only adolescent participants; and (3) use block-design fMRI. We propose a pathogenic model based on normal and AN-related neural and cognitive maturation during adolescence. We propose that underweight and delayed puberty—caused by genetic, environmental, and neurobehavioral factors—can affect brain and cognitive development and lead to impaired cognitive flexibility, which in turn sustains the perpetuation of aberrant behaviors in a vicious cycle. Moreover, greater punishment sensitivity causes a shift toward punishment-based learning, leading to greater anxiety and ultimately to excessive reappraisal over emotions. Treatments combining physiological and neurobehavioral rationales must be adopted to improve outcomes and prevent relapses.

© 2018 Elsevier Ltd In this review, we describe dielectric properties of biological tissues and liquids in the context of terahertz (THz) biophotonics. We discuss a model of the THz dielectric permittivity of water and water-containing media, which yields analysis of the relaxation and damped resonant molecules modes. We briefly describe modern techniques of THz spectroscopy and imaging employed in biophotonics with a strong emphasize on a THz time-domain spectroscopy. Furthermore, we consider the methods of sub-wavelength resolution THz imaging and the problem of THz wave delivery to hard to access tissues and internal organs. We consider the THz dielectric properties of biological solutions and liquids. Although strong absorption by water molecules prevents THz-waves from penetration of hydrated tissues and probing biological molecules in aqueous solutions, we discuss approaches for overcoming these drawbacks – novel techniques of freezing and temporal dehydration by application of hyperosmotic agents which have a potential for cancer detection. We review recent applications of THz technology in diagnosis of malignancies and aiding histology paying particular attention to the origin of contrast observed between healthy and pathological tissues. We consider recent applications of THz reflectometry in sensing the thinning dynamics of human pre-corneal tear film. Modern modalities of THz imaging, which relies on the concepts of multi-spectral and multi-temporal domains and employing the principles of color vision, phase analysis and tomography are discussed. Novel methods of THz spectra analysis based on machine learning, pattern recognition, chemical imaging and the revealing of the spatial distribution of various substances in a tissue, are analyzed. Advanced thermal model describing biological object irradiated by THz waves and phantoms mimicking the optical properties of tissues at THz frequencies are presented. Finally, application of the high-resolution THz spectroscopy in analytic chemistry, biology and medicine are described.

© 2018 Acta Materialia Inc. Quantitative measurement of pH and metabolite gradients by microscopy is one of the challenges in the production of scaffold-grown organoids and multicellular aggregates. Herein, we used the cellulose-binding domain (CBD) of the Cellulomonas fimi CenA protein for designing biosensor scaffolds that allow measurement of pH and Ca2+ gradients by fluorescence intensity and lifetime imaging (FLIM) detection modes. By fusing CBD with pH-sensitive enhanced cyan fluorescent protein (CBD-ECFP), we achieved efficient labeling of cellulose-based scaffolds based on nanofibrillar, bacterial cellulose, and decellularized plant materials. CBD-ECFP bound to the cellulose matrices demonstrated pH sensitivity comparable to untagged ECFP (1.9–2.3 ns for pH 6–8), thus making it compatible with FLIM-based analysis of extracellular pH. By using 3D culture of human colon cancer cells (HCT116) and adult stem cell-derived mouse intestinal organoids, we evaluated the utility of the produced biosensor scaffold. CBD-ECFP was sensitive to increases in extracellular acidification: the results showed a decline in 0.2–0.4 pH units in response to membrane depolarization by the protonophore FCCP. With the intestinal organoid model, we demonstrated multiparametric imaging by combining extracellular acidification (FLIM) with phosphorescent probe-based monitoring of cell oxygenation. The described labeling strategy allows for the design of extracellular pH-sensitive scaffolds for multiparametric FLIM assays and their use in engineered live cancer and stem cell-derived tissues. Collectively, this research can help in achieving the controlled biofabrication of 3D tissue models with known metabolic characteristics. Statement of Significance: We designed biosensors consisting of a cellulose-binding domain (CBD) and pH- and Ca2+-sensitive fluorescent proteins. CBD-tagged biosensors efficiently label various types of cellulose matrices including nanofibrillar cellulose and decellularized plant materials. Hybrid biosensing cellulose scaffolds designed in this study were successfully tested by multiparameter FLIM microscopy in 3D cultures of cancer cells and mouse intestinal organoids.

© 2018 Elsevier Ltd The variation of blood flow waveform in the internal carotid artery (ICA) with age is a well-documented hemodynamic phenomenon, but little is known about how such variation affects the characteristics of blood flow in aneurysms present in the region. In the study, hemodynamic simulations were conducted for 26 ICA aneurysms, with flow waveforms measured in the ICAs of young and older adults being used respectively to set the inflow boundary conditions. Obtained results showed that replacing the young-adult flow waveform with the older-adult one led to little changes (<10%) in simulated time-averaged wall shear stress (WSS), transient maximum WSS, relative residence time and trans-aneurysm pressure loss coefficient, but resulted in a marked increase (32.36 ± 17.24%) in oscillatory shear index (OSI). Frequency-domain wave analysis revealed that the progressive enhancement of low-frequency harmonics dominated the observed flow waveform variation with age and was a major factor contributing to the increase in OSI. Cross-sectional comparisons among the aneurysms further revealed that the degree of increase in OSI correlated positively with some specific morphological features of aneurysm, such as aspect ratio and size ratio. In summary, the study demonstrates that the variation in flow waveform with age augments the oscillation of WSS in ICA aneurysms, which underlies the importance of setting patient-specific boundary conditions in hemodynamic studies on cerebral aneurysms, especially those involving long-term patient follow-up or cross-sectional comparison among patients of different ages.

© 2018 Society of Photo-Optical Instrumentation Engineers (SPIE). We present the nanoparticle-enabled experimentally trained wavelet-domain denoising method for optical coherence tomography (OCT). It employs an experimental training algorithm based on imaging of a test-object, made of the colloidal suspension of the monodisperse nanoparticles and contains the microscale inclusions. The geometry and the scattering properties of the test-object are known a priori allowing us to set the criteria for the training algorithm. Using a wide set of the wavelet kernels and the wavelet-domain filtration approaches, the appropriate filter is constructed based on the test-object imaging. We apply the proposed approach and chose an efficient wavelet denoising procedure by considering the combinations of the decomposition basis from five wavelet families with eight types of the filtration threshold. We demonstrate applicability of the wavelet-filtering for the in vitro OCT image of human brain meningioma. The observed results prove high efficiency of the proposed OCT image denoising technique.

© 2018 IEEE. We have proposed an approach to improve the resolution of terahertz (THz) imaging using the effect of solid immersion - i.e. a reduction in the dimensions of the electromagnetic beam caustic by its formation in a free space, behind the medium possessing high refractive index. We have designed a THz solid immersion lens (SIL) comprised of a polymer wide-aperture aspherical singlet and a crystalline truncated sphere mounted in front of the image plane. We have proposed an approach for the object handling at the focal plane of the THz SIL. We have combined numerical simulations and experimental studies to demonstrate the advanced 0.2λ spatial resolution of the proposed THz SIL - it is beyond the 0.5λ Abbe limit. Finally, we have assembled the continuous-wave THz SIL imaging system and applied it for studying various objects with sub-wavelength variations of structure and dielectric properties.

© 2018 IEEE. We have proposed a method of THz solid immersion microscopy, which yields imaging soft biological tissues with the sub-wavelength resolution up to 0.2-wavelengths. To achieve this advanced resolution, it employs a solid immersion phenomenon - i.e. a reduction in the dimensions of the THz beam caustic by its formation on a small distance behind the medium featuring high refractive index. We have assembled an experimental setup, which realizes the principles of the THz solid immersion microscopy, and proposed an approach for handling the soft tissue at the object plane. This setup uses a backward-wave oscillator, as a source of continuous-wave THz radiation, and a Golay cell, as a detector of the THz field intensity. We have examined the resolution of the THz solid immersion microscopy using both numerical simulations and experimental studies. Finally, in order to highlight the prospective of the proposed THz imaging modality, we have applied the experimental setup for imaging of representative examples of biological tissues.

© 2018 IEEE. Modern progress in terahertz (THz) diagnostics of malignancies, including non-invasive, least-invasive and intraoperative techniques is briefly discussed. Special attention is paid to intraoperative diagnosis of brain tumors, which is a rapidly developing field nowadays. We discuss our recent results in this research field, which are associated with (i) in vitro studies the THz dielectric response of gelatin-embedded human brain tumors (including gliomas and meningiomas featuring different grades), (ii) analysis an ability for differentiation between normal and pathological tissues of the brain relying on the methods of THz spectroscopy and imaging, and, finally, (iii) development of novel THz instrumentation for the intraoperative detection of margins of tumors in order to guarantee its gross total resection.

© 2018, Springer International Publishing AG, part of Springer Nature.  Molecular oxygen (O 2 ) is a key player in cell mitochondrial function, redox balance and oxidative stress, normal tissue function and many common disease states. Various chemical, physical and biological methods have been proposed for measurement, real-time monitoring and imaging of O 2 concentration, state of decreased O 2 (hypoxia) and related parameters in cells and tissue. Here, we review the established and emerging optical microscopy techniques allowing to visualize O 2 levels in cells and tissue samples, mostly under in vitro and ex vivo, but also under in vivo settings. Particular examples include fluorescent hypoxia stains, fluorescent protein reporter systems, phosphorescent probes and nanosensors of different types. These techniques allow high-resolution mapping of O 2 gradients in live or post-mortem tissue, in 2D or 3D, qualitatively or quantitatively. They enable control and monitoring of oxygenation conditions and their correlation with other biomarkers of cell and tissue function. Comparison of these techniques and corresponding imaging setups, their analytical capabilities and typical applications are given.

© Kolosova et al. P62/SQSTM1, a multi-domain protein that regulates inflammation, apoptosis, and autophagy, has been linked to age-related pathologies. For example, previously we demonstrated that administration of p62/SQSTM1- encoding plasmid reduced chronic inflammation and alleviated osteoporosis and metabolic syndrome in animal models. Herein, we built upon these findings to investigate effect of the p62-encoding plasmid on an agerelated macular degeneration (AMD), a progressive neurodegenerative ocular disease, using spontaneous retinopathy in senescence-accelerated OXYS rats, as a model. Overall, the p62DNA decreased the incidence and severity of retinopathy. In retinal pigment epithelium (RPE), p62DNA administration slowed down development of the destructive alterations of RPE cells, including loss of regular hexagonal shape, hypertrophy, and multinucleation. In neuroretina, p62DNA prevented gliosis, retinal thinning, and significantly inhibited microglia/macrophages migration to the outer retina, prohibiting their subretinal accumulation. Taken together, our results suggest that the p62DNA has a strong retinoprotective effect in AMD.

© 2018 WILEY-VCH Verlag GmbH  &  Co. KGaA, Weinheim While noninvasive prenatal testing based on cell-free fetal DNA has recently revolutionized the field of aneuploidy screening in pregnancy, it remains limited to aneuploidy and microdeletion screening, and is unable to reliably detect single gene disorders. A number of recent studies have demonstrated the potential of circulating trophoblastic cells in providing cell-based noninvasive diagnosis with sequencing or array-based assays. However, considering the extreme rarity of these cells in blood, efficient, high-throughput, and clinically applicable enrichment technologies are yet to be developed. This study demonstrates for the first time the utility of inertial microfluidics for efficient isolation of trophoblastic cells from maternal peripheral blood. Under optimal operating conditions, high-recovery yields (79%) are obtained using a trophoblastic cell-line, which is subsequently confirmed with analysis of maternal blood. Feasibility of obtaining a diagnosis from cells isolated from a maternal sample is demonstrated in a case of confirmed fetal trisomy 21 in which six fetal cells are found in a 7 mL blood sample using fluorescence in situ hybridization. Finally, it is demonstrated that trophoblastic cells isolated using inertial microfluidics could be picked and subjected to a clinically validated sequencing assay, paving the way for further validation of this technology and larger clinical studies.

© 2018 IEEE. In this paper, we propose a computational approach for description of radiation transfer in a quasi-ordered medium and study the impact of scattering on electromagnetic wave propagation and image formation. It combines finite-difference time-domain method, Monte Carlo simulations, and radiative transfer theory. Using, as an example, terahertz (THz) imaging, we analyze the modulation transfer function (MTF) of the imaging system operated at 0.25 THz for scattering material layers placed between the object and the imaging plane. We experimentally study imaging of bar-pattern test objects through a quasi-ordered scattering medium. Both numerical and experimental results are in good agreement and demonstrate an impact of quasi-ordered scatterers on quality of THz images, i.e., particular combination of the electromagnetic wavelength and parameters of scattering materials could enhance MTF compared with ones with random particle structures.

© 2018, University of Kragujevac, Faculty of Science. All rights reserved. The aim of this study is to conduct several non-invasive methods for assessing the level of circulatory disturbance, elasticity and aging of skin in patients of different age groups in order to expand the diagnostic capabilities and evaluate the effectiveness of current research in aesthetic medicine. Clinical and instrumental exploration of 160 women aged 17 to 75 years with varying degrees of involutional skin changes was carried out. To objectify the assessment of skin condition, in all group of patients modern instrumental methods were used, such as: elastometry, ultrasound examination of the skin, laser Doppler flowmetry, transcutaneous oxygen tension. Concurrent implementation of several non-invasive methods for assessing the level of circulatory disturbance, elasticity and aging of the skin, allowed us to find new possibilities for studying the functional state of the skin. These methods extend the possibilities of ultrasonic research methods used today in aesthetic cosmetology. The obtained comparative data of elastometry, ultrasonography, laser Doppler flowmetry and transcutaneous oximetry in patients of different age groups showed the presence of elasticity and structure defect, skin thickness and subcutaneous fat, as well as microcirculation changes since 25 years and marked changes after 40 years.

© 2018 Media Sphera Publishing Group.All right reserved. Objective. This study aimed to assess the cognitive functions and cerebral blood flow measured with arterial spin labeling (ASL) and their possible correlations with vascular age in untreated middle-aged patients with grade 1-2 essential arterial hypertension (EAH). Methods. We examined 73 subjects aged 40-59 years (33 with EAH and 40 healthy volunteers [controls]). Neuropsychological assessment included Montreal Cognitive Assessment (MoCA), Trail Making test (part A and part B), Stroop Color and Word Test, verbal fluency test (phonemic verbal fluency and semantic verbal fluency), 10-item word list learning task. All subjects underwent brain MRI. MRI protocol included ASL. Vascular age was calculated by two techniques-using Framingham Heart Study risk tables and SCORE project scales. Results. Patients with EAH had lower performance on phonemic verbal fluency test and lower mean MoCA score (29.2±1.4 vs. 28.1±1.7 points) compared to controls (13.4±3.2, p=0.002; 29.2±1.4, p=0.001, respectively). White matter hyperintensities (WMH) were present in 7.5 % controls and in 51.5 % EAH patients (p=0.0002). Cerebral blood flow (CBF) in EAH patients was lower in both right (39.1±5.6 vs. 45.8±3.2 ml/100 g/min) and left frontal lobes of the brain (39.2±6.2 45.2±3.6 ml/100 g/min, respectively) compared to controls (p<0.001). EAH patients without WMH had lower CBF compared to controls (right frontal lobe: 39.5±5.1 ml/100 g/min, p=0.0002; left frontal lobe: 38.9±4.3 ml/100 g/min, p=0.00002). In EAH patients vascular age (57.7±7.4 and 64.6±11.0 years as measured by SCORE project scales and Framingham Heart Study risk tables, respectively) was significantly (p<0.001) greater than chronological one (50.2±6.2 years) and was significantly (p<0.001) higher than the corresponding values in the control group. Correlation analysis revealed negative significant associations between vascular age and MoCA score, phonemic verbal fluency test score and CBF. Conclusions. Treatment-naive middle-aged patients with uncomplicated grade 1-2 EAH compared to normotensive controls have lower mean scores in phonemic fluency test and MoCA, lower CBF, even in the absence of WMH, which correlates with vascular age, particularly with the value calculated by Framingham Heart Study risk tables. Early vascular ageing is important factor of brain impairment in hypertension in middle-aged patients even at early stages of EAH.

© 2018, Media Sphera Publishing Group. All rights reserved. The diagnosis of head injury should be based on certain principles. Each of them is important and has its own history. The authors summarize the experience of treatment of head injury using clinical and neuroimaging methods at the NN Burdenko Neurosurgery Institute (now the NN Burdenko National Research Center for Neurosurgery) for more than 30 years. The following principles of diagnosis of head injury were suggested and tested in clinical practice: severity of patient’s state; clinical syndromes; topical diagnosis; neuroimaging; phasicity; age-related approach; data synthesis; sufficiency; individual approach. Taken together, these principles provide complete personalized diagnosis and prognosis which allow choosing an optimal management of the patient. The strategy for better diagnosis, prognosis and treatment of head injury is the combined use of clinical, neuroimaging and ethical approaches.

© 2018 Russian Electronic Journal of Radiology.All right reserved. Purpose: In recent years, whole-body MRI have been increasingly used in the field of oncological radiology owing to its advantages such as: yield of high-quality diagnostic information in relatively short scan time, lack of radioisotope or intravenous contrast use, and comparingly low examination cost in contrast to traditional nuclear medicine techniques. Aim of this article is to bring the overview of whole-body MRI as a technique and current applications of its use in oncological radiology.

© Ima-Press Publishing House. All rights reserved. Cognitive impairment (CI) is common in patients with migraine; its causes and pathogenesis continue to be discussed. Some authors consider that migraine proper does not lead to decreased cognitive functions, neuroimaging changes in the brain white matter are asymptomatic in migraine; and CI in patients with this condition is caused by comorbidities (depression, anxiety disorder) and/or concurrent cerebrovascular and neurodegenerative diseases. Other authors report the pathogenetic role of migraine in the development of CI and the importance of the frequency of headache attacks and neuroimaging changes in the brain matter in migraine. The paper reviews clinical trials dealing with the prevalence, causes, and pathogenesis of CI in patients with migraine. It sets forth the current principles of prevention and treatment of CI in patients with this condition.

© ABC-press Publishing House. All rights reserved. Objectives to enhance the morphological diagnostic complex in order to predict postoperative outcomes in a more accurate way and to optimize patients with non-muscular invasive bladder cancer treatment. Materials and methods. The study included 34 patients from 25 to 71 years old underwent laser en-block resection, the most of them were males - 28. In 9 cases multiple carcinomas (2 or more) were found. Huge tumors (2 cm or more in one dimension) were resected in 6 patients. Results. The major part of tumors removed (n = 22) histologically appeared to be papillary urothelial carcinomas with low grade of malignancy and PUNLMP; in 6 cases G2 was verified, one tumor with high malignancy potention - G3. In 3 patients intramuscular invasion was found (invasive carcinoma T2) excluding them from the study. Discussion. Laser en-block resection of non-muscle-invasive bladder cancer appears to be the most optimal approach in operative treatment that provides representative histological material. For correct morphological estimate we recommend either to expand the resection zone to 1 cm which allows to remove circular resection margin or to take extra pinch biopsy from tumor crater (vertical margin). In 3 patients from our study positive circular margin was revealed histologically whereas foci of perineural and perivascular invasion were found in one case. A new subgrading of stage T1 depending on intramuscular invasion depth was suggested whereas the main criteria is the muscularis mucosae involvement. Conclusion. Morphological estimate of circular resection margin provides an ability to predict postoperative outcomes and correct the treatment in one or another way. Subgrading for T1-stage tumors is recommended for following correct postoperative prognosis and possibility of tumor recurrence.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Purpose. Evaluation of the morbidity structure and demonstration CT-semiotics of the main diseases in patients with nontraumatic acute abdomen. Materials and methods. 905 studies of the abdomen performed in 2016 in the State Clinical Hospital named after S.P. Botkin in patients with acute abdomen. The studies were conducted natively, with contrasting per os, with intravenous enhancement, depending on the expected pathology. Results. The most common causes of acute abdomen were: acute intestinal obstruction (27%), pancreatitis (9%), urolithiasis and its complications (8%), oncology directly and its complications (7%), inflammatory changes in the gallbladder and diliary ducts (4%), inflammatory changes in the kidneys (3%). Also significant weight in the structure of morbidity was perforation of the bowel (2.5%), mesenteric thrombosis (2%), extraorganic inflammatory changes (2%). Only 5% of cases failed to reliably detect signs of a pathological process in the presence of a clinical picture. The main characteristics of the risk group for the emergence of acute abdominal pathology, such as the age of 32-67 years, the male sex, are revealed. A more detailed analysis of risk factors within the statistically most significant nosological groups was also carried out. The diagnostic efficiency index of multislice computed tomography (CT) for the above diseases varied from 95% to 97%, the sensitivity and specificity of the method depending on the disease were 95-97.8% and 93.2-97%, respectively, p> 0.05. Conclusions. CT allows to determine the nature of the disease quite accurately in emergency medical care in patients with nontraumatic urgent abdominal pathology. The identification of a risk group in the structure of acute nontraumatic abdominal pathology facilitates early diagnosis and timely treatment.

© 2018 Ima-Press Publishing House. All rights reserved. With the development of current neuroimaging techniques, their role in diagnosing epilepsy is becoming more significant and that is not only in identifying the disease that plays a key role in epileptogenesis, but also in assisting a clinician in the subsequent formulation of the diagnosis, in correcting drug therapy, and, in some cases, in addressing the issue of surgical treatment in the patient. The priority technique in this case is magnetic resonance imaging (MRI) that has high sensitivity and specificity in defining the location of minor and more major lesions of the brain structure and that includes a set of current sequences that can obtain important diagnostic information about the functional state of the brain. This article highlights the International League Against Epilepsy guidelines for MRI in patients with suspected epilepsy, assesses the use of and briefly characterizes both structural and functional pulse sequences that are most commonly included in the epileptological protocol. It considers major pathological processes and evaluates anatomical and functional changes in the brain structure, which play an important role in epileptogenesis.