Сross-analysis of big data in accreditation of health specialists
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01.01.2018 |
Chelyshkova M.
Semenova T.
Naydenova N.
Dorozhkin E.
Malygin A.
Akhunov V.
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Electronic Journal of General Medicine |
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2 |
Ссылка
© 2018, Modestum Ltd.. All rights reserved. Objective: The relevance of this study is due to the mass accreditation of health professionals that is developing in Russia, which requires innovative measurement tools and opens new opportunities for a well-founded cross-analysis of specialists’ professional readiness quality. Purpose of the study: The purpose of this article is to present approved methodical approaches to the transformation of accreditation data into a format suitable for secondary analysis of medical schools graduates quality based on the requirements of Professional Standards. Method: The leading methods of secondary data analysis are: a) codification of indicators in the primary data accumulation array; b) statistical processing of study results (evaluation of the relationships between the arrays of primary data accumulation and instrumental data, the correlation of test scores obtained by accreditation results with the labor functions of Professional Standards); c) the creation of representative samples for data analysis. The implementation of methods is carried out in the mode of working with arrays of big data, which also uses the method of cross-analysis to identify additional factors that affect to specialists’ professional readiness quality. Results: As a results of the research, there were: 1) approaches to the codification of data in the array and their secondary analysis were developed; 2) three samples were constructed with an estimation of representativeness for different strata, including subjects, assignments and corresponding labor functions; 3) the matrix of primary data in the specialty “Pediatrics” was verified using the example of the results of students from 50 medical universities in Russia. Conclusion: Approbation of methods of secondary data analysis conducted on representative samples of the subjects showed the effectiveness of the developed approaches that should be used when analyzing large data sets in the procedures of certification or accreditation. The materials of the article can be useful for specialists in the field of assessing the quality of education or assessing the professional readiness of health professionals, managers, professors and pedagogical staff of medical schools, specialists of centers for independent assessment of qualifications.
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Clinical and radiological manifestations and anatomical and topographical rationale for a possible combined injury of the hip joint and proximal part of the sciatic nerve (clinical and experimental study)
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01.01.2018 |
Nikolenko V.
Chekhonatskiy A.
Osadchuk M.
Ilyasova E.
Osadchuk A.
Chekhonatskiy V.
Reshetnikov A.
Levchenko K.
Bahteeva N.
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Russian Electronic Journal of Radiology |
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0 |
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© 2018 Russian Electronic Journal of Radiology.All right reserved. Purpose: To study peculiarities of clinico-radiological and anatomico-topographic relationship of sciatic nerve and acetabulum. Materials and Methods: Two stages experimental research was conducted in vitro on 20 human corpses, died due to various reasons. Clinico-radiological study was carried out in vivo on 41 patients with injuries of sciatic nerve and acetabulum. Results: Research data can confidently state that topographic proximity of sciatic nerve to acetabulum especially to its posterior-upper edge determines high risk of nerve lesion at acetabulum fractures due to influence of bone fragments, formed hematoma, forming scars. Conclusion: Acetabulum fractures are potentially dangerous for possibility of simultaneous injury of sciatic nerve; in this case a patient has to be subjected to special examination with the purpose of his sciatic nerve status evaluation.
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Main directions of reducing patient irradiation doses in computed tomography
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01.01.2018 |
Matkevich E.
Sinitsyn V.
Zelikman M.
Kruchinin S.
Ivanov I.
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Russian Electronic Journal of Radiology |
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2 |
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© 2018 Russian Electronic Journal of Radiology.All right reserved. Purpose: To analyze and organize the basic techniques to reduce radiation exposure to patients with computed tomography (CT) scan of the head, chest, abdomen and pelvis. Materials and methods: The analysis of publications was carried out on the databases Scopus, Web of Science, MedLine and RINC. Results: The variants of the use of CT of the head, chest, heart, abdominal and pelvic organs in multidisciplinary institutions with different methods of reducing the dose burden on patients have been analyzed. Conclusion: The factors used to reduce the dose for CT can be systematized in three main ways: 1) methods that depend on the attending physician, radiologist and CT staff; 2) parameters of the research protocol; 3) features of CT-devices and software. Considering the factors reducing the radiation dose of patients in support of the need for CT examination, choice of parameters of the CT protocol, CT devices and software allows to significantly reduce the radiation burden on patients (by 10-78%) without compromising the quality of CT images. The development of methods to reduce the dose of irradiation of patients is extremely urgent, especially in screening, multiple CT studies and CT with contrast.
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Orthostatic hypotension: Definition, pathophysiology, classification, prognostic aspects, diagnostics and treatment
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01.01.2018 |
Ostroumova O.
Cherniaeva M.
Petrova M.
Golovina O.
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Rational Pharmacotherapy in Cardiology |
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1 |
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© 2018 Stolichnaya Izdatelskaya Kompaniya. All rights reserved. The urgency of the problem of orthostatic hypotension (OH) has increased in recent years. It was due to the high prevalence and its adverse effect on the prognosis and quality of life of patients, especially the elderly and oldest old. The purpose of this review was to summarize the contemporary domestic and foreign literature data about disease. The article presents an updated definition of OH, modern classification, pathophysiology, feature of the course of OH in the elderly, recommendations for diagnosis and treatment. Particular attention is paid to reviewing the results of scientific research on the influence of OH on the risk of developing coronary and cerebrovascular events and overall mortality. OH is one of the forms of orthostatic tolerance and diagnostic criteria were determined by the 2011 Consensus as a sustained fall of systolic blood pressure by at least 20 mm Hg and/or a diastolic blood pressure by 10 mm Hg within 3 min of standing. The prevalence of OH ranges depending on the age of the patients and the presence of a number of concomitant diseases: from 6% in healthy people without arterial hypertension up to 50% or more in people older than 75 years with a comorbid pathology. OH is an independent predictor of overall mortality and adverse cardiovascular events. OH is associated with an increased risk of serious adverse cerebrovascular and coronary events, and may also contribute to cognitive impairment and the development of dementia. For today, we have three clinical options OH: classical, early and delayed OH. In addition, OH is classified based on etiology-primary and secondary; and pathophysiological principle-neurogenic OH and not a neurogenic OH (or functional). The algorithm for identifying patients with a high risk of development of OH and diagnostic methods are also presented. Non-medicamentous and medicamentous methods of OH treatment are considered.
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Correlation of the aesthetic component of dental health and emotional state in patients with different anxiety levels
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01.01.2018 |
Lobach O.
Nikolenko V.
Rustamova E.
Lapina N.
Kochurova E.
Skorikova L.
Gavrushova L.
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Nevrologiya, Neiropsikhiatriya, Psikhosomatika |
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0 |
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© Ima-Press Publishing House. All rights reserved. Objective: to investigate the influence of the aesthetic component of dental health on the anxiety level and quality of life of socially active elderly patients. Patients and methods. A total of 32 patients aged 60 to 67 years who had a poor aesthetic appearance of the hard tissues of the front teeth were followed up. All the patients underwent determination of anxiety levels by the Spielberger-Hanin procedure and assessment of quality of life using an abbreviated 26-item version of the World Health Organization Quality of Life (WHOQOL-BREF-26) questionnaire; the updated Oral Health Impact Profile (OHIP-14) was also used. Aesthetic rehabilitation of vital front teeth was carried out using photo composite materials made in Russian and foreign countries. Results. Before treatment, the state anxiety scores were 54±1.4 scores; the trait anxiety ones were 41±1.2 scores; at 1 week after treatment, these were 42±0.5 and 39±0.6, respectively (p ≤ 0.05 for both indicators), and at 6 months, these were 44±0.5 and 43±0.7, respectively. Conclusion. The aesthetic component of dental health in socially active elderly patients is directly proportional to quality of life and inversely proportional to the level of trait or state anxiety. Russian and foreign photo composite restorative materials showed equal sustained performance.
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Non-motor disorders in cervical dystonia
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01.01.2018 |
Tolmacheva V.
Nodel M.
Saloukhna N.
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Nevrologiya, Neiropsikhiatriya, Psikhosomatika |
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0 |
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© Ima-Press Publishing House. All rights reserved. Botulinum toxin injection therapy is the mainstay for managing patients with motor manifestations of dystonia. It is important to identify possible cognitive and mental disorders, sleep and perceptual disorders (non-motor disorders) in these patients. Correction of these disorders will be able to optimize treatment and to improve quality of life of patients.
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A novel peptide dendrimer LTP efficiently facilitates transfection of mammalian cells
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01.01.2018 |
Kozhikhova K.
Andreev S.
Shilovskiy I.
Timofeeva A.
Gaisina A.
Shatilov A.
Turetskiy E.
Andreev I.
Smirnov V.
Dvornikov A.
Khaitov M.
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Organic and Biomolecular Chemistry |
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3 |
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© 2018 The Royal Society of Chemistry. One of the urgent problems of gene therapy is the search for effective transfection methods. Synthetic cationic peptides (CPs) are considered to be one of the most promising approaches for intracellular transport of oligonucleotides. Almost unlimited possibilities of the architectural design of CPs (linear and cyclic structures with a variation of chirality as well as dendrimers) make CPs an effective tunable carrier in this field. Cationic peptide dendrimers (PDs), as a relatively new direction, have significant advantages as gene delivery vehicles by virtue of non-natural ϵ-amide bonds that significantly increase their resistance to proteolysis. Moreover they also possess much lower cytotoxicity than linear peptides, which is crucial for the potential clinical application of CPs. In a further development of oligonucleotide delivery systems, we have synthesized a collection of 14 CPs, including linear peptides, lipopeptides and PDs. Their activity was evaluated by transfection of 293T cells with plasmids containing reporter genes encoding luciferase or a green fluorescent protein. The obtained results demonstrated that the greatest activity was exhibited by PDs, particularly LTP, an arginine-rich peptide dendrimer, which possesses low cytotoxic and hemolytic activity. The peptide exhibited high cell-penetrating activity, confirmed by fast dissipation of the membrane potential of cells probed by dis-C3-(5). The quantitative analysis of labelled LTP in tissue samples of mice revealed that the Cy5-LTP/siRNA complexes have a reasonable tropism to lung tissues.
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Hydrogel-assisted neuroregeneration approaches towards brain injury therapy: A state-of-the-art review
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01.01.2018 |
Kornev V.
Grebenik E.
Solovieva A.
Dmitriev R.
Timashev P.
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Computational and Structural Biotechnology Journal |
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3 |
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© 2018 The Authors Recent years have witnessed the development of an enormous variety of hydrogel-based systems for neuroregeneration. Formed from hydrophilic polymers and comprised of up to 90% of water, these three-dimensional networks are promising tools for brain tissue regeneration. They can assist structural and functional restoration of damaged tissues by providing mechanical support and navigating cell fate. Hydrogels also show the potential for brain injury therapy due to their broadly tunable physical, chemical, and biological properties. Hydrogel polymers, which have been extensively implemented in recent brain injury repair studies, include hyaluronic acid, collagen type I, alginate, chitosan, methylcellulose, Matrigel, fibrin, gellan gum, self-assembling peptides and proteins, poly(ethylene glycol), methacrylates, and methacrylamides. When viewed as tools for neuroregeneration, hydrogels can be divided into: (1) hydrogels suitable for brain injury therapy, (2) hydrogels that do not meet basic therapeutic requirements and (3) promising hydrogels which meet the criteria for further investigations. Our analysis shows that fibrin, collagen I and self-assembling peptide-based hydrogels display very attractive properties for neuroregeneration.
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Focus on Internal Urethrotomy as Primary Treatment for Untreated Bulbar Urethral Strictures: Results from a Multivariable Analysis
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01.01.2018 |
Barbagli G.
Fossati N.
Montorsi F.
Balò S.
Rimondi C.
Larcher A.
Sansalone S.
Butnaru D.
Lazzeri M.
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European Urology Focus |
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0 |
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© 2018 European Association of Urology Background: The use of internal urethrotomy for treatment of urethral stricture remains a controversial topic in urology. Objective: To investigate outcomes and predictors of failure for internal urethrotomy as primary treatment for untreated bulbar urethral strictures. Design, setting, and participants: We performed a retrospective analysis of patients who underwent internal urethrotomy. Patients with bulbar urethral stricture who did not receive any previous treatment were included. Patients with traumatic, penile or posterior urethral strictures, lichen sclerosus, failed hypospadias repair, or stricture length >4 cm were excluded. Outcome measurements and statistical analysis: The primary outcome was treatment failure. Kaplan-Meyer plots were used to depict treatment failure–free survival. Univariate and multivariable Cox regression analyses were used to test the association between predictors (age, body mass index, diabetes, history of smoking, etiology, stenosis type and length, preoperative maximum flow [pQmax]) and treatment failure. Results and limitations: Overall, 136 patients were included. The median stricture length was 2 cm. Median follow-up was 55 mo. At 5-yr follow-up the failure-free survival rate was 57%. On univariate analysis, diabetes, nonidiopathic etiology, stricture length of 3–4 cm, and pQmax were significantly associated with treatment failure. These predictors were included in a multivariable analysis, in which pQmax was the only significant predictor of treatment failure. Conclusions: Failure of internal urethrotomy for untreated bulbar urethral strictures greatly depends on pQmax flow at uroflowmetry. Patients with pQmax > 8 ml/s have a high probability of success, while patients with pQmax <5 ml/s have a low probability of success. Patient summary: The use of internal urethrotomy in patients with an untreated bulbar urethral stricture should only be considered in selected cases. The use of internal urethrotomy in patients with untreated bulbar urethral stricture should be suggested only in selected cases.
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Cognitive disorders and dementia in old patients with arterial hypertension
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01.01.2018 |
Ostroumova O.
Starodubova A.
Ostroumova T.
Chernyaeva M.
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Kardiologiya |
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0 |
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© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. The article describes the definition of dementia, its diagnostic criteria, classification. Differences in the pathogenesis and clinical manifestations of different types of dementia are considered. The issues of interrelation of arterial hypertension and the risk of development of cognitive disorders and dementia in old and very old people are discussed in detail. Data on the effect of antihypertensive drugs of different groups on the risk of dementia and the state of cognitive functions are presented. The evidence base of dihydropyridine calcium antagonist amlodipine and thiazide-like diuretic indapamide-retard is discussed with respect to the prevention of dementia and cognitive decline and their beneficial effect on cognitive function in patients with arterial hypertension.
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Dependence of Anterior Active Rhinomanometry Indices on Nasal Obstructive Disorders in Children with Atopic Bronchial Asthma Complicated by Nasal Symptoms
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01.01.2018 |
Eliseeva T.
Krasilnikova S.
Babaev S.
Novozhilov A.
Ovsyannikov D.
Ignatov S.
Kubysheva N.
Shakhov A.
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BioMed Research International |
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2 |
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© 2018 Tatyana I. Eliseeva et al. Background. Atopic bronchial asthma (BA) in children is associated with upper airways pathology (UAP). Among them, a combination of allergic rhinitis (AR) and nasal obstructive disorders (NOD), including hypertrophy of the pharyngeal tonsil (HPT) and anomalies of the intranasal structures (AINS), is abundant. In such patients, anterior active rhinomanometry (AARM) is an important method of examining nasal patency. However, NOD can influence the AARM parameters in children with BA and nasal symptoms, and this effect must be taken into account in clinical practice. Study goal was to elucidate the effect of NOD on rhinomanometric parameters in this group of patients. Methods. Total of 66 children with BA and AR were examined with AARM, rhinovideoendoscopy, spirometry, and standard clinical tests allowing revealing the structure of comorbid pathologies. In order to avoid the influence of anthropometric parameters of children and their age on AARM parameters, a special index of reduced total nasal airflow was used. Results. It has been established that NOD, especially HPT, have a significant negative impact on the indices of anterior active rhinomanometry during the periods of both AR remission and AR exacerbation. The effect of AINS is much weaker and was remarkable only in combination with HPT.
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A hybrid micromixer with planar mixing units
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01.01.2018 |
Bazaz S.
Mehrizi A.
Ghorbani S.
Vasilescu S.
Asadnia M.
Warkiani M.
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RSC Advances |
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7 |
Ссылка
© The Royal Society of Chemistry. The application of microfluidic systems in chemical and biological assays has progressed dramatically in recent years. One of the fundamental operations that microfluidic devices must achieve is a high mixing index. Of particular importance is the role of planar mixing units with repetitive obstacles (MURO) in the formation of micromixers. To date, a myriad of planar passive micromixers has been proposed. However, a strategy for the combination of these units to find an efficient planar mixer has not been investigated. As such, five different MURO have been selected to form a “hybrid micromixer,” and their combination was evaluated via numerical and experimental methods. These mixing units include ellipse-like, Tesla, nozzle and pillar, teardrop, and obstruction in a curved mixing unit. Since these units have distinctive dimensions, dynamic and geometric similarities were used to scale and connect them. Afterwards, six slots were designated to house each mixing unit. Since the evaluation of all possible unit configurations is not feasible, the design of experiment method is applied to reduce the total number of experiments from 15 625 to 25. Following this procedure, the “hybrid” micromixer proposed here, comprising Tesla, nozzle and pillar, and obstruction units, shows improved performance for a wide range of Re (i.e., mixing index of >90% for Re 0.001-0.1, 22-45) over existing designs. The use of velocity profiles, concentration diagrams, vorticity and circulation plots assist in the analysis of each unit. Comparison of the proposed “hybrid” micromixer with other obstacle-based planar micromixers demonstrates improved performance, indicating the combination of planar mixing units is a useful strategy for building high-performance micromixers.
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Characteristics of Bacillus pumilus B-13176 strain producing metabolites with fungicide and antibacterial activities to Aspergillus niger and Staphylococcus aureus (MRSA)
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01.01.2018 |
Kuzin A.
Tagaev A.
Ovchinnikova T.
Kuznetsova N.
Nikolaenko M.
Morozova O.
Azizbekyan R.
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Biotekhnologiya |
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1 |
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© 2018. A strain B-13176 that manifested the antibacterial and fungicidal activities has been isolated by screening of sporiferous bacteria and identified as Bacillus pumilus on the basis of the analysis of variable regions of 16S RNA sequences. Cultural and morphological characteristics of the strain were studied, the dynamics of the synthesis of fungicidal and antibacterial metabolites and their location in culture were determined, and their resistance to physicochemical factors was investigated. It was shown that the strain possesses a pronounced activity against the fungi of Aspergillus niger and the methycillinresistant bacteria of Staphylococcus aureus strain (MRSA). The culture liquid of the strain was fractioned using centrifugation, ultrafiltration, extraction and HPLC. Mass-spectrometry was used to show that the Bacillus pumilus B-13176 strain produces active thermostable protease-resistant metabolites of the peptide origin that are located in the CL pellet (the fungicidal component) and in the CL supernatant (the antibacterial component).
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Cities of federal significance: Analysis of the main indicators characterizing medical care for children with cancer in 2013–2017. An ecological study
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01.01.2018 |
Rykov M.
Turabov I.
Punanov Y.
Safonova S.
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Onkopediatria |
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1 |
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© 2018 Paediatrician Publishers, LLC. All rights reserved. Background: Moscow and St. Petersburg are cities of federal significance with the largest number of children and consequently a large number of primary patients identified annually. Objective: Our aim was to analyze the main indicators characterizing the delivery of medical care for children with cancer in cities of federal significance. Methods: The operative reports for 2013–2017 of the Department of Health of Moscow, the Ministry of Health of the Moscow Region, the Health Committee of the Government of St. Petersburg, and the Health Committee of the Leningrad Region were analyzed. Results. In 2013–2017 in the Russian Federation, 18 090 primary patients were identified, 2734 (15.1%) of them in the analyzed subjects: in Moscow — 1315 (7.3%), in the Moscow Region — 492 (2.7%), in St. Petersburg — 697 (3.9%), in the Leningrad Region — 230 (1.3%). For 5 years, the number of primary patients increased in Moscow by 18.1%, in St. Petersburg — by 36%, in the Leningrad Region — by 2.5%. In the Moscow Region, the number of primary patients decreased by 2.3%. The incidence in Moscow increased by 5.3% (from 11.3 per 100 000 of children aged 0–17 in 2013 to 11.9 in 2017), in St. Petersburg — by 18.1% (from 14.9 in 2013 to 17.6 in 2017). The incidence in the Moscow Region fell by 20% (from 11.8 in 2013 to 9.4 in 2017), in the Leningrad Region by 4.9% (from 14.4 in 2013 to 13.7 in 2017). Mortality in 2016–2017 in Moscow decreased by 37.5% (from 6.4 per 100 thousand children’s population 0–17 years to 4), in the Moscow Region — by 50% (from 2 to 1), in St. Petersburg increased by 50% (from 2 to 3), in the Leningrad Region — by 12.5% (from 2.4 to 2.7). The one-year mortality rate in Moscow increased by 3.7% (from 8.3% in 2016 to 12% in 2017), in the Moscow Region — by 3.5% (from 5.4 to 8.9% %), in St. Petersburg — by 3.9% (from 2.5 to 6.4%). In the Leningrad Region, the one-year mortality rate decreased from 6.5% in 2016 to 0 in 2017. The number of pediatric oncological beds did not change in the Moscow Region (0.4 per 10,000 children aged 0–17 years), St. Petersburg (0.9), and the Leningrad Region (0). In Moscow and St. Petersburg patients were not identified actively in 2016–2017; in the Moscow Region, their percentage decreased from 34.2 to 7.3, in the Leningrad Region — from 8.7 to 0. In Moscow, the number of pediatric oncological beds increased by 50% (from 0.6 to 0.9). The number of oncologists increased in the Moscow Region from 0.009 per 10 000 children aged 0–17 years to 0.06 (66.7%), in St. Petersburg from 0.09 to 0.12 (+33.3%), in the Leningrad Region — from 0 to 0.03. In Moscow, the number of pediatric oncologists decreased from 0.13 to 0.11 (-15.3%). Conclusion: Defects of statistical data were revealed. Patients were not identified during routine preventive examinations which indicate a low oncologic alertness of district pediatric physicians. Delivery of medical care for children with cancer and the statistical data accumulation procedures should be improved.
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60S dynamic state of bacterial ribosome is fixed by Yeast mitochondrial initiation factor 3
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01.01.2018 |
Levitskii S.
Derbikova K.
Baleva M.
Kuzmenko A.
Golovin A.
Chicherin I.
Krasheninnikov I.
Kamenski P.
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PeerJ |
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2 |
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Copyright © 2018 Levitskii et al. The processes of association and dissociation of ribosomal subunits are of great importance for the protein biosynthesis. The mechanistic details of these processes, however, are not well known. In bacteria, upon translation termination, the ribosome dissociates into subunits which is necessary for its further involvement into new initiation step. The dissociated state of the ribosome is maintained by initiation factor 3 (IF3) which binds to free small subunits and prevents their premature association with large subunits. In this work, we have exchanged IF3 in Escherichia coli cells by its ortholog from Saccharomyces cerevisiae mitochondria (Aim23p) and showed that Yeast protein cannot functionally substitute the bacterial one and is even slightly toxic for bacterial cells. Our in vitro experiments have demonstrated that Aim23p does not split E. coli ribosomes into subunits. Instead, it fixes a state of ribosomes characterized by sedimentation coefficient about 60S which is not a stable structure but rather reflects a shift of dynamic equilibrium between associated and dissociated states of the ribosome. Mitochondria-specific terminal extensions of Aim23p are necessary for “60S state” formation, and molecular modeling results point out that these extensions might stabilize the position of the protein on the bacterial ribosome.
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The forensic medical estimation of the biological age of the corpse based on the morphological changes in the skin
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01.01.2018 |
Pigolkin Y.
Dolzhansky O.
Zolotenkova G.
Ametrin M.
Zolotenkov D.
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Sudebno-Meditsinskaya Ekspertiza |
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0 |
Ссылка
© 2018, Media Sphera Publishing Group. All rights reserved. The objective of the present work was the immunohistochemical evaluation of the age-related dynamics of apoptosis-associated proteins contained in the human skin epidermis. We studied the samples of skin tissues obtained during the forensic medical expertises of 100 corpses of the subjects who died in the consequence of acute blood loss in the absence of injuries or pathological changes in the skin (56 men and 44 women at the age varying from 5 to 85 years). The results of this study give evidence that the histoimmunological investigations of the skin tissues can be carried out with the use of the mmunohistochemical Ki67, bcl-2, and p53 markers for the more accurate determination of the biological age of the deceased subjects. The quantitative characteristics thus obtained serve as reliable indicators of the chronic changes in the skin and can be used as the components of the combined diagnostic procedures.
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Inhibition of HIF-prolyl 4-hydroxylases as a promising approach to the therapy of cardiometabolic diseases
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01.01.2018 |
Aitbaev K.
Murkamilov I.
Fomin V.
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Terapevticheskii Arkhiv |
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0 |
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© 2018 Media Sphera Publishing Group. All rights reserved. Prolyl-4-hydroxylases of hypoxia-inducible factor (HIF-P4Hs) are enzymes that, under the conditions of normoxia, cause degradation of the HIF-transcriptional protein, which regulates a number of metabolic processes, including erythropoiesis, glucose level and lipid metabolism. In hypoxic conditions, on the contrary, their activity is suppressed and HIF stabilization takes place. This mechanism, i.e. stabilization of HIF by inhibition of HIF-P4Hs was the basis for the development of drugs designed for treatment of renal anemia, which are currently in stages 2 and 3 of clinical trials and are showing encouraging results. Recently, it has also been reported that inhibition of HIF-P4Hs can be effective in treatment of cardiometabolic diseases - coronary heart disease, hypertension, obesity, metabolic syndrome, diabetic cardiomyopathy and atherosclerosis. The review, based on the most recent data, discusses in detail molecular mechanisms of therapeutic effect of HIF-P4Hs inhibition in these pathological conditions and provides evidence that these mechanisms are associated with HIF stabilization and gene expression, improving perfusion and endothelial function, reprogramming metabolism from oxidative phosphorylation to anaerobic glycolysis, reducing inflammation and having beneficial effect on the innate immune system.
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LC-MS/MS identification and structural characterization of main biodegradation products of nitroproston-A novel prostaglandin-based pharmaceutical compound
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01.01.2018 |
Mesonzhnik N.
Moskaleva N.
Shestakova K.
Kurynina K.
Baranov P.
Gretskaya N.
Serkov I.
Lyubimov I.
Bezuglov V.
Appolonova S.
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Drug Metabolism Letters |
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1 |
Ссылка
© 2018 Bentham Science Publishers. Background: Nitroproston is a novel prostaglandin-based compound modified by NO-donating groups with potential application in obstructive respiratory diseases such as asthma and obstructive bronchitis. Nitroproston has been extensively studied using various pharmacological models. Its biological stability is still uncertain. Objective: The aim of the present study was to evaluate Nitroproston stability in vitro, as well as to identify and characterize its major biodegradation products. Methods: The principal biodegradation products of Nitroproston were identified in vitro using liquid chromatography/ion trap – time-of-flight mass-spectrometry. The postulated structure of metabolites was confirmed using authentic reference standards. Rat, rabbit and human plasma and human whole blood samples were used for comparative in vitro degradation study. Nitroproston and its biodegradation products in biological samples were measured by liquid chromatography/triple –stage quadrupole mass spectrometry. Results: Nitroproston is rapidly hydrolyzed in rat plasma to generate glycerol-1,3-dinitrate and prostaglandin E2 . The latter can undergo conversion to cyclopentenone prostaglandins A2 and B2 . Thereby less than 5% of the parent compound was observed in rat plasma at the first moment of incubation. A similar pattern was observed for rabbit plasma where half-life (T1/2) of Nitroproston was about 2.0 minutes. Nitroproston biodegradation rate for human plasma was the slowest (T1/2 = 2.1 h) among tested species, occurred more rapidly in whole blood (T1/2 = 14.8 min). Conclusion: It was found that Nitroproston is rapidly hydrolyzed in rodent compared to human plasma incubations. Whereas Nitroproston is relatively stable in human plasma an enhanced hydrolytic activity was observed in whole human blood incubations. Extensive metabolism of Nitroproston in human whole blood was mainly associated with red blood cells. The observed interspecies variability highlights the need of suitable animal model selection for Nitroproston follow-up PK/PD studies.
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Placental expression level of the PON1, PON2, and PON3 genes in pstients with uncomplicated pregnancy and preeclampsia
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01.01.2018 |
Antipova N.
Levakov S.
Sheshukova N.
Obukhova E.
Pavlyukov M.
Shakhparonov M.
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Akusherstvo i Ginekologiya (Russian Federation) |
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0 |
Ссылка
© Bionika Media Ltd. Objective. To determine the expression level of the genes encoding the paraoxonase family enzymes (PON1, PON2, and PON3) in the placentas of women with uncomplicated pregnancy and in the development of preeclampsia Materials and methods. The investigation enrolled 26 pregnant women aged 24 to 35 years, including 14 women with normal pregnancy and 12 with preeclampsia. The expression of the PON1, PON2, and PON3 genes was analyzed by real-time PCR using the primers specific to these genes. Results. Women whose pregnancy was complicated by preeclampsia showed a significant decrease in the placental expression of the PON2 gene. The lowest PON2 gene expression was found in the placentas of women with severe preeclampsia. There were no significant differences in the placental expression level of the PON1 and PON3 genes in women with preeclampsia compared to healthy women. Conclusion. In women with preeclampsia, the placental PON2 gene expression decreases; however, the expression level of the PON1 and PON3 genes does not differ from that of the PON1 and PON3 genes in the placentas of patients with physiological pregnancy. The placental expression of the PON2 gene depends on the severity of preeclampsia; is lower in severe preeclampsia than in moderate preeclampsia.
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The technology of laser fabrication of cell 3D scaffolds based on proteins and carbon nanoparticles
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01.01.2018 |
Gerasimenko A.
Zhurbina N.
Kurilova U.
Polokhin A.
Ryabkin D.
Savelyev M.
Suetina I.
Mezentseva M.
Ichkitidze L.
Ignatov D.
Garcia-Ramirez M.
Guzman Gonzalez J.
Podgaetsky V.
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Proceedings of SPIE - The International Society for Optical Engineering |
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© 2018 SPIE. The technology of cell 3D scaffolds laser fabrication is developed. 3D scaffolds are designed to repair osteochondral defects, which are poorly restored during the organism's life. The technology involves the use of an installation, the laser beam of which moves along a liquid nanomaterial and evaporates it layer by layer. Liquid nanomaterial consists of the water-protein (collagen, albumin) suspension with carbon nanoparticles (single-walled carbon nanotubes). During laser irradiation, the temperature in the region of nanotubes defects increases and nanotubes are combined into the scaffold. The main component of installation is a continuous laser operating at wavelengh of 810 nm. The laser beam moves along 3 coordinates, which makes it possible to obtain samples of the required geometric shape. The internal and surface structure of the samples at the micro- A nd nanoscale levels were studied using the X-ray microtomography and scanning electron microscopy. In vitro studies of cell growth during 48 and 72 hours demonstrated the ability of cell 3D scaffolds to support the proliferation of osteoblasts and chondroblasts. Using fluorescence and atomic force microscopy, it was found that the growth and development of cells on a sample with a larger concentration of nanotubes occurred faster compared to samples with a smaller concentration of nanotubes.
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