Motivational readiness of students of the Ural state medical university to work with elderly patients

Social and demographic changes in society pose new challenges to improving health and preserving the functional abilities of older persons, creating conditions for their psychological and social well-being. In this regard, in the structure of professional training of specialists with higher medical education, the need for them to develop то psychological and educational competence, focused on the social and psychological determinants of the health of older patients, is increasingСоциально-демографические изменения в обществе ставят новые задачи, связанные с укреплением здоровья и с сохранением функциональных способностей пожилых людей, с созданием условий для их психологического и социального благополучия. В связи с этим в структуре профессиональной подготовки специалистов с высшим медицинским образованием возрастает необходимость формирования у них социально-психолого-педагогической компетентности, ориентированной на социальные и психологические детерминанты здоровья пожилых пациенто

Assessment of anti-inflammatory tumor treatment efficacy by longitudinal monitoring employing sonographic micro morphology in a preclinical mouse model

<p>Abstract</p> <p>Background</p> <p>With the development of increasingly sophisticated three-dimensional volumetric imaging methods, tumor volume can serve as a robust and reproducible measurement of drug efficacy. Since the use of molecularly targeted agents in the clinic will almost certainly involve combinations with other therapeutic modalities, the use of volumetric determination can help to identify a dosing schedule of sequential combinations of cytostatic drugs resulting in long term control of tumor growth with minimal toxicity. The aim of this study is to assess high resolution sonography imaging for the in vivo monitoring of efficacy of Infliximab in pancreatic tumor.</p> <p>Methods</p> <p>In the first experiment, primary orthotopic pancreatic tumor growth was measured with Infliximab treatment. In the second experiment, orthotopic tumors were resected ten days after inoculation of tumor cells and tumor recurrence was measured following Infliximab treatment. Tumor progression was evaluated using 3D high resolution sonography.</p> <p>Results</p> <p>Sonography measurement of tumor volume in vivo showed inhibitory effect of Infliximab on primary tumor growth in both non-resected and resected models. Measurement of the dynamics of tumor growth by sonography revealed that in the primary tumor Infliximab is effective against established tumors while in the resection model, Infliximab is more effective at an early stage following tumor resection. Infliximab treatment is also effective in inhibiting tumor growth growth as a result of tumor cell contamination of the surgical field.</p> <p>Conclusions</p> <p>Clinical application of Infliximab is feasible in both the neoadjuvant and adjuvant setting. Infliximab is also effective in slowing the growth of tumor growth under the peritoneum and may have application in treating peritoneal carcinomatosis. Finally the study demonstrates that high resolution sonography is a sensitive imaging modality for the measurement of pancreatic tumor growth.</p

Modification of Silicon Carbide Ceramics by Hierarchical Systems “Multi-Walled Carbon Nanotubes-Silicon”

С использованием метода реакционного спекания под давлением были получены образцы пористой керамики на основе карбида кремния. В качестве связующего использовали мелкокристаллический кремний в совокупности с многослойными углеродными нанотрубками (МУНТ) с нанесенными частицами кремния. Давление при прессовании составляло 30 МПа, температура варьировалась в диапазоне 1420–1480 °C, содержание МУНТ от 0 до 4 масс. % и связующего Si от 20 до 25 масс. %. Структура полученной керамики исследована методами оптической и растровой электронной микроскопии. Были установлены основные закономерности формирования структуры спеченной модифицированной керамики в зависимости от условий проведения спекания. Методом трёхточечного изгиба были исследованы физико-механические свойства полученных образцовSamples of porous ceramics based on silicon carbide were obtained by reactive sintering under pressure. Fine-crystalline silicon was used as a binder in combination with multi-walled carbon nanotubes (MWCNTs) with deposited silicon particles. The pressing pressure was 30 MPa, the temperature was varied in the range of 1420–1480 °C, the MWCNTs content was from 0 to 4 wt. %, and silicon binder from 20 to 25 wt. %. The structure of the obtained ceramics was studied by optical and scanning electron microscopy. The main regularities of the structure formation of sintered modified ceramics are established depending on the sintering conditions. To study the physical and mechanical properties of the obtained samples, the three-point flexural test was use

Time-dependent effects of imatinib in human leukaemia cells: a kinetic NMR-profiling study

The goal of this study was to evaluate the time course of metabolic changes in leukaemia cells treated with the Bcr-Abl tyrosine kinase inhibitor imatinib. Human Bcr-Abl+ K562 cells were incubated with imatinib in a dose-escalating manner (starting at 0.1 μM with a weekly increase of 0.1 μM imatinib) for up to 5 weeks. Nuclear magnetic resonance spectroscopy and liquid-chromatography mass spectrometry were performed to assess a global metabolic profile, including glucose metabolism, energy state, lipid metabolism and drug uptake, after incubation with imatinib. Initially, imatinib treatment completely inhibited the activity of Bcr-Abl tyrosine kinase, followed by the inhibition of cell glycolytic activity and glucose uptake. This was accompanied by the increased mitochondrial activity and energy production. With escalating imatinib doses, the process of cell death rapidly progressed. Phosphocreatine and NAD+ concentrations began to decrease, and mitochondrial activity, as well as the glycolysis rate, was further reduced. Subsequently, the synthesis of lipids as necessary membrane precursors for apoptotic bodies was accelerated. The concentrations of the Kennedy pathway intermediates, phosphocholine and phosphatidylcholine, were reduced. After 4 weeks of exposure to imatinib, the secondary necrosis associated with decrease in the mitochondrial and glycolytic activity occurred and was followed by a shutdown of energy production and cell death. In conclusion, monitoring of metabolic changes in cells exposed to novel signal transduction modulators supplements molecular findings and provides further mechanistic insights into longitudinal changes of the mitochondrial and glycolytic pathways of oncogenesis

Сорбция платинохлористоводородной кислоты модифицированными углеродными материалами

The influence of oxidation and impregnation of the carbon materials on the sorption of H2PtCl6 was studied. The state of platinum on the surface was studied with the SEM, EDS, XPS and XAFS methods.Изучено влияние окисления и импрегнации углеродного материала на сорбцию H2[PtCl6]. Методами РЭМ, ЭДС, РФЭС и ЕXAFS изучено состояние платины на поверхности

Pattern Recognition Analysis of Proton Nuclear Magnetic Resonance Spectra of Brain Tissue Extracts from Rats Anesthetized with Propofol or Isoflurane

BACKGROUND: General anesthesia is routinely used as a surgical procedure and its safety has been endorsed by clinical outcomes; however, its effects at the molecular level have not been elucidated. General anesthetics influence glucose metabolism in the brain. However, the effects of anesthetics on brain metabolites other than those related to glucose have not been well characterized. We used a pattern recognition analysis of proton nuclear magnetic resonance spectra to visualize the changes in holistic brain metabolic phenotypes in response to the widely used intravenous anesthetic propofol and the volatile anesthetic isoflurane. METHODOLOGY/PRINCIPAL FINDINGS: Rats were randomized into five groups (n = 7 each group). Propofol and isoflurane were administered to two groups each, for 2 or 6 h. The control group received no anesthesia. Brains were removed directly after anesthesia. Hydrophilic compounds were extracted from excised whole brains and measured by proton nuclear magnetic resonance spectroscopy. All spectral data were processed and analyzed by principal component analysis for comparison of the metabolite profiles. Data were visualized by plotting principal component (PC) scores. In the plots, each point represents an individual sample. The propofol and isoflurane groups were clustered separately on the plots, and this separation was especially pronounced when comparing the 6-h groups. The PC scores of the propofol group were clearly distinct from those of the control group, particularly in the 6-h group, whereas the difference in PC scores was more subtle in the isoflurane group and control groups. CONCLUSIONS/SIGNIFICANCE: The results of the present study showed that propofol and isoflurane exerted differential effects on holistic brain metabolism under anesthesia

Metabolomic Profiling of Drug Responses in Acute Myeloid Leukaemia Cell Lines

Combined bezafibrate (BEZ) and medroxyprogesterone acetate (MPA) exert unexpected antileukaemic activities against acute myeloid leukaemia (AML) and these activities are associated with the generation of reactive oxygen species (ROS) within the tumor cells. Although the generation of ROS by these drugs is supported by preceding studies including our own, the interrelationship between the cellular effects of the drugs and ROS generation is not well understood. Here we report the use of NMR metabolomic profiling to further study the effect of BEZ and MPA on three AML cell lines and to shed light on the underlying mechanism of action. For this we focused on drug effects induced during the initial 24 hours of treatment prior to the onset of overt cellular responses and examined these in the context of basal differences in metabolic profiles between the cell lines. Despite their ultimately profound cellular effects, the early changes in metabolic profiles engendered by these drugs were less pronounced than the constitutive metabolic differences between cell types. Nonetheless, drug treatments engendered common metabolic changes, most markedly in the response to the combination of BEZ and MPA. These responses included changes to TCA cycle intermediates consistent with recently identified chemical actions of ROS. Notable amongst these was the conversion of α-ketoglutarate to succinate which was recapitulated by the treatment of cell extracts with exogenous hydrogen peroxide. These findings indicate that the actions of combined BEZ and MPA against AML cells are indeed mediated downstream of the generation of ROS rather than some hitherto unsuspected mechanism. Moreover, our findings demonstrate that metabolite profiles represent highly sensitive markers for genomic differences between cells and their responses to external stimuli. This opens new perspectives to use metabolic profiling as a tool to study the rational redeployment of drugs in new disease settings

Номограмма для прогнозирования госпитальной летальности у пациентов с COVID-19, находившихся в отделении реанимации и интенсивной терапии

The objective: to develop a predictive model for assessing the risk of death in patients with COVID-19 admitted to the intensive care unit (ICU).Subjects and Methods. This was a single-center retrospective cohort study of hospital mortality in patients admitted to ICU of V.P. Demikhov City Clinical Hospital from March 6 to June 3, 2020.Results. Case histories of 403 patients were analyzed. In-hospital 30-day mortality among patients treated in ICU was 44.9% (181/403 patients). A multivariate analysis showed that significant predictors of death in patients with COVID-19 were the age of 60 years or more (adj. OR 3.84; 95% CI 1.56‒9.44, p = 0.003), COPD (adj. OR 2.35; 95% CI 1.12‒4.95, p = 0.024), peripheral artery diseases (adj. OR: 5.08; 95% CI 1.87‒13.76, p = 0.001) and CKD stage 3b and higher (adj. OR 4.58; 95% CI 2.36‒8.90, p &lt; 0.001), LDH 300 IU/l or more (adj. OR 3.05; 95% CI 1.23‒7.58, p = 0.016), and CRP 200 mg/l or more (adj. OR 3.65; 95% CI 1.95‒6.85, p &lt; 0.001). Predictive model quality: AUC = 0.811 [0.733‒0.874], p &lt; 0.001.Conclusions. A nomogram to assess the risk of death in patients with COVID-19 has been developed. It includes the assessment of age, history of COPD, CKD stage 3b and higher, peripheral artery diseases, and monitoring of LDH and CRP.Цель: разработать прогностическую модель оценки риска развития летального исхода в течение 30 дней после госпитализации у пациентов с COVID-19, проходивших лечение в отделении реанимации и интенсивной терапии (ОРИТ).Материалы и методы. Проведено одноцентровое ретроспективное когортное исследование госпитальной летальности пациентов, находящихся на лечении в ОРИТ ГБУЗ «ГКБ им. В. П. Демихова ДЗМ» в период с 6 марта по 3 июня 2020 г.Результаты. Проведен анализ историй болезней 403 пациентов. Итоговая 30-дневная летальность составила 44,9% (181/403). Значимыми предикторами летального исхода у пациентов с COVID-19 оказались: возраст 60 лет и более (adj. OR 3,84; 95%-ный ДИ 1,56‒9,44, p = 0,003), наличие в анамнезе хронической обструктивной болезни легких (adj. OR 2,35; 95%-ный ДИ 1,12‒4,95, p = 0,024), заболеваний периферических артерий (adj. OR 5,08; 95%-ный ДИ 1,87‒13,76, p = 0,001) и хронической болезни почек 3b стадии и выше (adj. OR 4,58; 95%-ный ДИ 2,36‒8,90, p &lt; 0,001), значение уровня лактатдегидрогеназы 300 МЕ/л и более (adj. OR 3,05; 95%-ный ДИ 1,23‒7,58, p = 0,016) и С-реактивного белка 200 мг/л и более (adj. OR 3,65; 95%-ный ДИ 1,95‒6,85, p &lt; 0,001). Качество прогностической модели: AUC = 0,811 [0,733‒0,874], p &lt; 0,001.Выводы. Разработана номограмма для оценки риска наступления летального исхода у пациентов с COVID-19, предполагающая оценку возраста, наличия в анамнезе хронической обструктивной болезни легких, хронической болезни почек 3b стадии и выше, заболеваний периферических артерий, мониторинг лактатдегидрогеназы и С-реактивного белка

Metabolic assessment of a novel chronic myelogenous leukemic cell line and an imatinib resistant subline by 1H NMR spectroscopy

The goal of this study was to examine metabolic differences between a novel chronic myelogenous leukemic (CML) cell line, MyL, and a sub-clone, MyL-R, which displays enhanced resistance to the targeted Bcr-Abl tyrosine kinase inhibitor imatinib. 1H nuclear magnetic resonance (NMR) spectroscopy was carried out on cell extracts and conditioned media from each cell type. Both principal component analysis (PCA) and specific metabolite identification and quantification were used to examine metabolic differences between the cell types. MyL cells showed enhanced glucose removal from the media compared to MyL-R cells with significant differences in production rates of the glycolytic end-products, lactate and alanine. Interestingly, the total intracellular creatine pool (creatine + phosphocreatine) was significantly elevated in MyL-R compared to MyL cells. We further demonstrated that the MyL-R cells converted the creatine to phosphocreatine using non-invasive monitoring of perfused alginate-encapsulated MyL-R and MyL cells by in vivo 31P NMR spectroscopy and subsequent HPLC analysis of extracts. Our data demonstrated a clear difference in the metabolite profiles of drug-resistant and sensitive cells, with the biggest difference being an elevation of creatine metabolites in the imatinib-resistant MyL-R cells

A Cell-based Computational Modeling Approach for Developing Site-Directed Molecular Probes

Modeling the local absorption and retention patterns of membrane-permeant small molecules in a cellular context could facilitate development of site-directed chemical agents for bioimaging or therapeutic applications. Here, we present an integrative approach to this problem, combining in silico computational models, in vitro cell based assays and in vivo biodistribution studies. To target small molecule probes to the epithelial cells of the upper airways, a multiscale computational model of the lung was first used as a screening tool, in silico. Following virtual screening, cell monolayers differentiated on microfabricated pore arrays and multilayer cultures of primary human bronchial epithelial cells differentiated in an air-liquid interface were used to test the local absorption and intracellular retention patterns of selected probes, in vitro. Lastly, experiments involving visualization of bioimaging probe distribution in the lungs after local and systemic administration were used to test the relevance of computational models and cell-based assays, in vivo. The results of in vivo experiments were consistent with the results of in silico simulations, indicating that mitochondrial accumulation of membrane permeant, hydrophilic cations can be used to maximize local exposure and retention, specifically in the upper airways after intratracheal administration