Репозиторий Университета

© 2019 Elsevier B.V. Objective: Being increasingly faced with the problem of pediatric nasal septal perforations, we have found that the surgical management of nasal septal perforations in children is not widely described in the litrature. The objective of our study was to demonstrate the results of different surgical techniques, including two original endoscopic techniques, in the septal perforation repair in children. Methods: 24 children, ranging between 6 and 17 years of age, with nasal septal perforations were operated using different endoscopic techniques from February 2015 to May 2019 at the special tertiary referral clinic. Apart from well-known techniques, such as anterior ethmoidal artery flap, intranasal bipedicled advancement flap, sublabial flap, free temporal fascia graft, we used two original techniques – inverted edges technique and cross-septal returned flap. Results: The total rate of complete perforation closure was 79% (19 of 24 patients). Regarding the reduction of symptoms, the efficacy of surgery was approaching 100%. The combination of inverted edges technique and anterior ethmoidal artery septal flap demonstrated the best results with no reperforations in all 10 cases. Using cross-septal returned flap, we achieved complete closure of perforation in 5 (83%) of 6 patients. The remaining techniques were performed rare and showed relatively low rates of success. There were 2 cases of complications (oronasal fistula), both developed in patients with sublabial mucosal flap. Conclusion: Use of endoscopic assistance, vascularized mucoperichondrial flaps and bilateral closure demonstrates high effectiveness in septal perforation surgical repair in children. Level of evidence: 4.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. In the context of a post-antibiotic era, the phenomenon of microbial allolysis, which is defined as the partial killing of bacterial population induced by other cells of the same species, may take on greater significance. This phenomenon was revealed in some bacterial species such as Streptococcus pneumoniae and Bacillus subtilis, and has been suspected to occur in some other species or genera, such as enterococci. The mechanisms of this phenomenon, as well as its role in the life of microbial populations still form part of ongoing research. Herein, we describe recent developments in allolysis in the context of its practical benefits as a form of cell death that may give rise to developing new strategies for manipulating the life and death of bacterial communities. We highlight how such findings may be viewed with importance and potential within the fields of medicine, biotechnology, and pharmacology.

© 2019 Elsevier Inc. Hyponatremia has been associated with an increased risk of demise in several malignancies. The aim of the current study was to evaluate its prognostic value in patients with castration-resistant prostate cancer. In 186 patients planned for docetaxel chemotherapy, we detected an association between hyponatremia and decreased survival (P = .04). We suggest conducting further well-designed studies including full workup of hyponatremia.

© 2019 Elsevier B.V. A new sample extraction protocol was developed for pharmacokinetic studies of dabigatran with high-performance liquid chromatography separation - electrospray ionization time-of-flight mass spectrometry analysis. After protein precipitation with acetonitrile, free dabigatran and its metabolites are separated into water phase by water-dichloromethane liquid-liquid extraction to purify the sample from proteins and endogenous lipophilic compounds. Chromatographic separation was achieved on an Agilent Zorbax SB-CN column (150 × 4.6 mm, 5 µm)) using 0.1% aqueous solution of formic acid and acetonitrile (80:20) as the mobile phase. Agilent Zorbax SB-CN column was selected to improve sample resolution and to avoided early elution of dabigatran previously seen when using a C18 column. The extended calibration curve was constructed from 5 to 1000 ng/L while precision and accuracy were assessed at four levels across the linear dynamic ranges. Within-run precision was <5.6% and the between-run precision was <3.9%. The method accuracy ranged from 89.8% to 104.4%. The developed method was successfully applied to 30 patient samples to evaluate antithrombotic efficacy and anticoagulant activity of dabigatran following knee endoprosthesis surgery.

Chronic hepatitis B virus infection (CHB) caused by the hepatitis B virus (HBV) is one of the most common viral infections in the world. Reactivation of HBV infection is a life-threatening condition observed in patients with CHB receiving chemotherapy or other medications. Although HBV reactivation is commonly attributed to immune suppression, other factors have long been suspected to play a role, including intracellular signaling activated in response to DNA damage. We investigated the effects of DNA-damaging factors (doxorubicin and hydrogen peroxide) on HBV reactivation/replication and the consequent DNA-damage response. Dose-dependent activation of HBV replication was observed in response to doxorubicin and hydrogen peroxide which was associated with a marked elevation in the mRNA levels of ataxia-telangiectasia mutated (ATM) and ATM- and RAD3-related (ATR) kinases. Downregulation of ATM or ATR expression by shRNAs substantially reduced the levels of HBV RNAs and DNA. In contrast, transcriptional activation of ATM or ATR using CRISPRa significantly increased HBV replication. We conclude that ATM and ATR are essential for HBV replication. Furthermore, DNA damage leading to the activation of ATM and ATR transcription, results in the reactivation of HBV replication.

© 2019 by the authors. This paper reveals the mechanism of nanowelding a branched network of single-walled carbon nanotubes (SWCNTs) used as a framework for the formation of protein-polymer matrices with albumin, collagen, and chitosan. It is shown that the introduction of certain point defects into the structure of SWCNTs (single vacancy, double vacancy, Stone-Wales defect, and a mixed defect) allows us to obtain strong heating in defective regions as compared to ideal SWCNTs. The wavelengths at which absorption reaches 50% are determined. Non-uniform absorption of laser radiation along with inefficient heat removal in defective regions determines the formation of hot spots, in which nanowelding of SWCNTs is observed even at 0.36 nm between contacting surfaces. The regularities of formation of layered protein-polymer matrices and the features of their interaction with cell membrane are revealed. All studies are carried out in silico using high-precision quantum approaches.

© 2019 Wolters Kluwer Health, Inc. Purpose of reviewThe current review summarizes contemporary decellularization and hydrogel manufacturing strategies in the field of tissue engineering and regenerative medicine.Recent findingsDecellularized extracellular matrix (ECM) bioscaffolds are a valuable biomaterial that can be purposed into various forms of synthetic tissues such as hydrogels. ECM-based hydrogels can be of animal or human origin. The use of human tissues as a source for ECM hydrogels in the clinical setting is still in its infancy and current literature is scant and anecdotal, resulting in inconclusive results.SummaryThus far the methods used to obtain hydrogels from human tissues remains a work in progress. Gelation, the most complex technique in obtaining hydrogels, is challenging due to remarkable heterogeneity of the tissues secondary to interindividual variability. Age, sex, ethnicity, and preexisting conditions are factors that dramatically undermine the technical feasibility of the gelation process. This is contrasted with animals whose well defined anatomical and histological characteristics have been selectively bred for the goal of manufacturing hydrogels.

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Astrocytes, a class of morphologically and functionally diverse primary homeostatic neuroglia, are key keepers of neural tissue homeostasis and fundamental contributors to brain defence in pathological contexts. Failure of astroglial support and defence facilitate the evolution of neurological diseases, which often results in aberrant synaptic transmission, neurodegeneration and death of neurones. In Alzheimer’s disease (AD), astrocytes undergo complex and multifaceted metamorphoses ranging from atrophy with loss of function to reactive astrogliosis with hypertrophy. Astroglial asthenia underlies reduced homeostatic support and neuroprotection that may account for impaired synaptic transmission and neuronal demise. Reactive astrogliosis which mainly develops in astrocytes associated with senile plaque is prominent at the early to moderate stages of AD manifested by mild cognitive impairment; downregulation of astrogliosis (reflecting astroglial paralysis) is associated with late stages of the disease characterised by severe dementia. Cell-specific therapies aimed at boosting astroglial supportive and defensive capabilities and preventing astroglial paralysis may offer new directions in preventing, arresting, or even curing AD-linked neurodegeneration.

© 2019 Elsevier Ltd Adhesion G protein-coupled receptor L3 (ADGRL3, LPHN3) has putative roles in neuronal migration and synapse function. Various polymorphisms in ADGRL3 have been linked with an increased risk of attention deficit/hyperactivity disorder (ADHD). In this study, we examined the characteristics of Adgrl3-deficient mice in multiple behavioural domains related to ADHD: locomotive activity, impulsivity, gait, visuospatial and recognition memory, sociability, anxiety-like behaviour and aggression. Additionally, we investigated the effect of Adgrl3-depletion at the transcriptomic level by RNA-sequencing three ADHD-relevant brain regions: prefrontal cortex (PFC), hippocampus and striatum. Adgrl3 −/− mice show increased locomotive activity across all tests and subtle gait abnormalities. These mice also show impairments across spatial memory and learning domains, alongside increased levels of impulsivity and sociability with decreased aggression. However, these alterations were absent in Adgrl3 +/− mice. Across all brain regions tested, the numbers of genes found to exhibit differential expression was relatively small, indicating a specific pathway of action, rather than a broad neurobiological perturbation. Gene-set analysis of differential expression in the PFC detected a number of ADHD-relevant pathways including dopaminergic synapses as well as cocaine and amphetamine addiction. The Slc6a3 gene coding for the dopamine transporter was the most dysregulated gene in the PFC. Unexpectedly, several neurohormone/peptides which are typically only expressed in the hypothamalus were found to be dysregulated in the striatum. Our study further validates Adgrl3 constitutive knockout mice as an experimental model of ADHD while providing neuroanatomical targets for future studies involving ADGRL3 modified models. This article is part of the Special Issue entitled ‘Current status of the neurobiology of aggression and impulsivity’.

© 2019, Pediatria Ltd. All rights reserved. Urinary tract infection (UTI) is one of the most common diseases of the urinary system faced by pediatricians. Objective of the research: To study and analyze outpatient records of patients in their first year of life, sent to a nephrologist for a consultation due to microbial inflammatory changes in urine general analysis. Materials and methods: Outpatient records of 160 children aged from 1 month to 1 year, who were sent in 2017 for a consultation with a nephrologist in consultative diagnostic clinic of G.N. Speransky City Children's Hospital № 9 with directing diagnosis UTI. Results: Authors performed an assessment of guiding diagnoses, age and gender composition of patients, an assessment of life anamnesis and disease clinical symptoms dynamics before referring patients for consultation with a nephrologist. The article discusses mistakes and issues of diagnosing UTI in young children. Conclusion: Authors substantiates pediatrician’s tactics for timely UTI diagnosis in young children and correct tactics of managing these patients.

© 2019, Pediatria Ltd. All rights reserved. The question of the methodology for assessing the physical development (PD) of the child population remains debatable. An analytical, prospective, cohort study (8300 children) was performed. A comparative evaluation of 4 methods of PD assessment based on informativity criterion is presented. The ratio of methods and content of regulatory documents of the Ministry of Health of the Russian Federation is shown. Advantages of the complex technique were revealed, which is important for pediatricians, since the stated deviation in child's PD allows to determine the amount of diagnostic, preventive, and health-improving measures and recommendations for a healthy lifestyle. Within the confines of Decade of Childhood, it is necessary to eliminate the existing contradictions in normative base of the Ministry of Health of the Russian Federation, medical statistics, and medical personnel training.

© Copyright © 2019 Lechermeier, Zimmer, Lüffe, Lesch, Romanos, Lillesaar and Drepper. The transport of glucose across the cell plasma membrane is vital to most mammalian cells. The glucose transporter (GLUT; also called SLC2A) family of transmembrane solute carriers is responsible for this function in vivo. GLUT proteins encompass 14 different isoforms in humans with different cell type-specific expression patterns and activities. Central to glucose utilization and delivery in the brain is the neuronally expressed GLUT3. Recent research has shown an involvement of GLUT3 genetic variation or altered expression in several different brain disorders, including Huntington’s and Alzheimer’s diseases. Furthermore, GLUT3 was identified as a potential risk gene for multiple psychiatric disorders. To study the role of GLUT3 in brain function and disease a more detailed knowledge of its expression in model organisms is needed. Zebrafish (Danio rerio) has in recent years gained popularity as a model organism for brain research and is now well-established for modeling psychiatric disorders. Here, we have analyzed the sequence of GLUT3 orthologs and identified two paralogous genes in the zebrafish, slc2a3a and slc2a3b. Interestingly, the Glut3b protein sequence contains a unique stretch of amino acids, which may be important for functional regulation. The slc2a3a transcript is detectable in the central nervous system including distinct cellular populations in telencephalon, diencephalon, mesencephalon and rhombencephalon at embryonic and larval stages. Conversely, the slc2a3b transcript shows a rather diffuse expression pattern at different embryonic stages and brain regions. Expression of slc2a3a is maintained in the adult brain and is found in the telencephalon, diencephalon, mesencephalon, cerebellum and medulla oblongata. The slc2a3b transcripts are present in overlapping as well as distinct regions compared to slc2a3a. Double in situ hybridizations were used to demonstrate that slc2a3a is expressed by some GABAergic neurons at embryonic stages. This detailed description of zebrafish slc2a3a and slc2a3b expression at developmental and adult stages paves the way for further investigations of normal GLUT3 function and its role in brain disorders.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The physicochemical and technological properties of an interpolymer complex of polymethyacrylic acid and polyethylene glycol, known under its commercial name “Polymer Carrier Composition” (FGUP Science Research Institute of Polymers, Russia), were studied. This polymer is an excipient substance used in the technology of solid dosage forms as a matrix former and as a film-forming agent for making long-acting and slow-release formulations. With the aim of widening the potential uses of the polymer carrier composition, the solubility of the polymer in aqueous solutions and organic solvents was studied, along with the technological and surfactant properties of the polymer; the critical gel-forming concentration was also determined. Experimental samples of tablets and oral gels of model substances with similar physicochemical properties were prepared, based on different concentrations of the Polymer Carrier Composition, and the technological, rheological, and biopharmaceutical properties of these were studied. The potential for using the polymer in both hard and soft dosage forms to obtain prolonged-release medicinal formulations is demonstrated.

© 2018, Pleiades Publishing, Ltd. The gene for Kunitz peptidase inhibitor-like protein (KPILP) contains nested alternative open reading frame (aORF) that controls expression of the maternal mRNA. The content of NbKPILP mRNA in intact leaves of Nicotiana benthamiana plant is low but increases significantly upon extended dark exposure or when foreign nucleic acid is overexpressed in the cells. The NbKPILP gene promoter along with the expressed nested aORF are likely to play an important role in maintaining the levels of NbKPILP mRNA. To elucidate the role of NbKPILP promoter, we isolated a fragment of N. benthamiana chromosomal DNA upstream of the NbKPILP transcription start, sequenced it, and created constructs in which reporter E. coli uidA gene coding for β-D-glucuronidase (GUS) was placed under control of the NbKPILP promoter. By assessing the efficacy of uidA mRNA synthesis directed by the NbKPILP promoter and 35S promoter of the cauliflower mosaic virus in a transient expression system, we showed that the levels of GUS accumulation were comparable for both promoters. Prolonged incubation of the agroinjected plants in the darkness stimulated accumulation of the uidA mRNA directed by the NbKPILP promoter. Our experiments indicate that along with regulation at the transcriptional level, expression of NbKPILP mRNA can be affected by expression of the nested aORF controlled by the polypurine block (PPB) located upstream of its start codon, since introduction of mutations in the PPB resulted in significant accumulation of the NbKPILP mRNA. Nucleotide replacement in the aORF start codon led to the drastic increase in the amounts of NbKPILP mRNA and its protein product.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Articular hyaline cartilage is extensively hydrated, but it is neither innervated nor vascularized, and its low cell density allows only extremely limited self-renewal. Most clinical and research efforts currently focus on the restoration of cartilage damaged in connection with osteoarthritis or trauma. Here, we discuss current clinical approaches for repairing cartilage, as well as research approaches which are currently developing, and those under translation into clinical practice. We also describe potential future directions in this area, including tissue engineering based on scaffolding and/or stem cells as well as a combination of gene and cell therapy. Particular focus is placed on cell-based approaches and the potential of recently characterized chondro-progenitors; progress with induced pluripotent stem cells is also discussed. In this context, we also consider the ability of different types of stem cell to restore hyaline cartilage and the importance of mimicking the environment in vivo during cell expansion and differentiation into mature chondrocytes.

© 2018 The Author(s). Background: The approaches to the diagnosis and treatment of chronic spontaneous urticaria (CSU) differ in various parts of the world. We sought to determine the adherence to international and national urticaria guidelines as well as the motives to deviate from the guidelines among physicians worldwide. Methods: A web-based questionnaire was created and launched via e-mail by the World Allergy Organization (WAO) to representatives of all WAO Member Societies, the members of the American Academy of Allergy, Asthma & Immunology (AAAAI) and the members of the WAO Junior Members Group (JMG), regardless of the specialty, affiliation, or nationality in March 2017. Results: We received 1140 completed surveys from participating physicians from 99 countries. Virtually all participants (96%) were aware of at least one urticaria guideline and reported that they follow a guideline. However, one in five physicians who follow a guideline (22%) reported to deviate from it. Reliance on own clinical experience is the most frequent reason for deviation from guidelines or not following them (44%). Young (< 40 years) and less experienced physicians more often follow a guideline and less often deviate than older and experienced ones. Physicians who follow a urticaria guideline showed higher rates of routinely ordering a complete blood count, the erythrocyte sedimentation rate, C-reactive protein, anti-thyroid antibodies, and thyroid-stimulating hormone and of performing the autologous serum skin test as compared to those who do not. Physicians who follow a urticaria guideline showed higher rates of using second generation antihistamines as their first-line treatment of CSU (p = 0.001) and more frequently observed higher efficacy of these drugs (or had more confidence that it would work, p < 0.019) as compared to those who do not follow the guidelines. Conclusions: Physicians' characteristics (e.g. age, clinical experience, and specialty) and country specifics and regional features (e.g. availability of drugs for CSU treatment) importantly influence adherence to urticaria guidelines and CSU patient care and should be addressed in more detail in future research.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Research results supporting the manufacturing technology for floating prolonged-release oral tablets based on a hydrophilic matrix with the nonselective α-adrenoblocker proroxan are presented.Wet granulation of the effervescent ingredients with the matrix produced tablets with the required buoyancy lag-time, float time, and proroxan release kinetics.

© The Author(s) 2018. Purpose: To review our experience with peripherally inserted central catheters in pediatric cancer patients. Methods: The analysis included 353 patients (3 months up to 17 years, mean age 11.2 years) with a variety of cancers diseases, which in 2011–2016, 354 peripherally inserted central catheters were placed. All settings are carried out using ultrasound guidance. In 138 (39%) patients, external anatomical landmarks were used and in 216 (61%) intraoperative fluoroscopy. Results: Maximal duration of the line was 1.3 years, the lowest 1.5 months, and average 6.3 months. Among the technical difficulties during placement, most frequently have been the migration of the distal end of the catheter into the internal jugular vein against blood flow—32 (9%) patients. In one (0.3%) case, we were unable to catheterize the patient’s vein. Among the most common complications of operation were marked peripherally inserted central catheter clot occlusion of the lumen—26 (7.3%) cases. Symptomatic catheter-related thrombosis was observed in 16 (4.5%) cases. Catheter-related blood stream infections were not reported. Removal of peripherally inserted central catheters related to the complications was performed in 30 (8.5%) patients who were later implanted venous ports. Conclusion: Peripherally inserted central catheters are recommend to use in the treatment of children with cancer. There should be trained nursing staff to minimize the risk of complications.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Our study confirmed the capacity of S. pyogenes strains to form biofilms on abiotic surfaces. Chains of streptococci surrounded by bluish film were seen under a microscope after alcian blue staining of the preparations grown on slides. On ultrathin sections in transmission electron microscope, the extracellular matrix (indicator of biofilm maturity) became visible after staining with alcian blue. Microscopy of the sections shows structures characteristic of a biofilm in spaces between the cells. Scanning electron microscopy also demonstrates the presence of a biomembrane. Importantly that type 1M strain forming in fact no membranes when cultured on plastic plates (Costar) formed biofilms on the glass. It seems that the conditions for the biofilm formation on the plastic and on the glass differ, due to which the exopolymeric matrices formed on different surfaces vary by biochemical composition.

© 2018, Pleiades Publishing, Inc. This is the first study to observe a 25% atrophy of m. vastus lateralis and a decrease in the size of type I and II muscle fibers (by 35 and 44%, respectively) using magnetic resonance imaging (MRI) in women after five to seven years of alcohol intoxication. The decrease in muscle volume is due to the predominant destruction of contractile apparatus as compared with other components.