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One of the fundamental problems in management is the issue of correlation of occupational rationality and human factor. The highest recognition of this issue was achieved in the Russian management thought in the early 1900s. The authors have concentrated their attention on the Russian management thought, since it is studied less in comparison with classical Western management schools. This article analyzes the works by the major philosophers and theoreticians of management, their approaches and attitudes to the mentioned issue are considered, the main results of conferences on scientific organization of labor held in the USSR are studied. The main aim of the article is retrospective analysis and systematization of approaches of the Russian scientists to the correlation between occupational rationality and human capital. The results of the study are arranged in the form of correlation matrix of various sides and attitudes on this issue in the works by various Russian philosophers of management. It should be mentioned that solution to this problem is relevant at present, since digitization minimizes the significance and opportunities of human factor.

BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium. METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction. RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions. CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.

The study aims the estimation of incidence of traumas and poisonings, and mortality from them at workers of the Russian nuclear industry, participants in the rectification of the consequences of the accident at the Chernobyl Atomic Electric Power Station, in view of their social structure. Material and methods. Carrying out this research, we used the information base of the Register of the persons exposed by radiation after the Chernobyl accident. There had been registered as of January, 1, 1998: liquidators of 1986-1987 years — 12882 people (men — 84,3%), liquidators of 1988-1990 years —2313 people (men — 88,3%). There had been presented parameters of case rate and mortality of men, separately workers and employees of the given cohort. Results. Lower level of traumas and poisonings incidence at employees had been revealed (2-2,4 times lower), than at the workers, the mortality of traumas and poisonings at employees were also 1,1-2,9 times lower (on the average — in 2,0 times) is revealed. The alcoholism essentially raises a traumatism at liquidators. The traumatism above at the liquidators, suffering a chronic alcoholism, in 1,9-3,3 times. The distinctions in coefficients of the mortality from traumas and poisonings and the incidence by them for age groups of the men-liquidators were revealed. Conclusion. The essential difference in parameters of men-liquidators' health, workers of the nuclear industry, and workers shows that a social factor renders significant influence on health of a studied contingent of persons. Age features in many respects define value of parameters of incidence of traumas and poisonings and death rates from them a studied contingent. In radiation epidemiological researches it is necessary to consider biological and social factors necessarily.

Abstract Background Glioblastoma multiforme (GBM) stands as a formidable challenge in oncology because of its aggressive nature and severely limited treatment options. Despite decades of research, the survival rates for GBM remain effectively stagnant. A defining hallmark of GBM is a highly acidic tumor microenvironment, which is thought to activate pro-tumorigenic pathways. This acidification is the result of altered tumor metabolism favoring aerobic glycolysis, a phenomenon known as the Warburg effect. Low extracellular pH confers radioresistant tumors to glial cells. Notably GPR68, an acid sensing GPCR, is upregulated in radioresistant GBM. Usage of Lorazepam, which has off target agonism of GPR68, is linked to worse clinical outcomes for a variety of cancers. However, the role of tumor microenvironment acidification in GPR68 activation has not been assessed in cancer. Here we interrogate the role of GPR68 specifically in GBM cells using a novel highly specific small molecule inhibitor of GPR68 named Ogremorphin (OGM) to induce the iron mediated cell death pathway: ferroptosis. Method OGM was identified in a non-biased zebrafish embryonic development screen and validated with Morpholino and CRISPR based approaches. Next, A GPI-anchored pH reporter, pHluorin2, was stably expressed in U87 glioblastoma cells to probe extracellular acidification. Cell survival assays, via nuclei counting and cell titer glo, were used to demonstrate sensitivity to GPR68 inhibition in twelve immortalized and PDX GBM lines. To determine GPR68 inhibition’s mechanism of cell death we use DAVID pathway analysis of RNAseq. Our major indication, ferroptosis, was then confirmed by western blotting and qRT-PCR of reporter genes including TFRC. This finding was further validated by transmission electron microscopy and liperfluo staining to assess lipid peroxidation. Lastly, we use siRNA and CRISPRi to demonstrate the critical role of ATF4 suppression via GPR68 for GBM survival. Results We used a pHLourin2 probe to demonstrate how glioblastoma cells acidify their microenvironment to activate the commonly over expressed acid sensing GPCR, GPR68. Using our small molecule inhibitor OGM and genetic means, we show that blocking GPR68 signaling results in robust cell death in all thirteen glioblastoma cell lines tested, irrespective of genetic and phenotypic heterogeneity, or resistance to the mainstay GBM chemotherapeutic temozolomide. We use U87 and U138 glioblastoma cell lines to show how selective induction of ferroptosis occurs in an ATF4-dependent manner. Importantly, OGM was not-acutely toxic to zebrafish and its inhibitory effects were found to spare non-malignant neural cells. Conclusion These results indicate GPR68 emerges as a critical sensor for an autocrine pro-tumorigenic signaling cascade triggered by extracellular acidification in glioblastoma cells. In this context, GPR68 suppresses ATF4, inhibition of GPR68 increases expression of ATF4 which leads to ferroptotic cell death. These findings provide a promising therapeutic approach to selectively induce ferroptosis in glioblastoma cells while sparing healthy neural tissue.

Abstract Gut microbiota metabolites have been mechanistically linked to inflammatory pathway activation and atherosclerosis, which are major causes of vascular stiffness (VS). Aiming to investigate if the gut microbiome might be involved in VS development, we performed a cross-sectional study (n = 3,087), nested within the population-based European Prospective Investigations into Cancer and Nutrition (EPIC) Potsdam. We investigated the correlation of the gut microbiota (alpha diversity and taxa abundance) with 3 vascular stiffness measures: carotid-femoral (PWV), aortic augmentation index (AIX) and ankle-brachial index (ABI). Shannon index was not significantly associated with VS but the number of observed Amplicon Sequence Variants (ASV) was positively associated with PWV and AIX. We found a total of 19 ASVs significantly associated with at least one VS measure in multivariable-adjusted models. One ASV (classified as Sutterella wadsworthensis) was associated with 2 VS measures, AIX (− 0.11 ± 0.04) and PWV (-0.14 ± 0.03). Other examples of ASVs associated with VS were Collinsella aerofaciens, previously reported to be affected by diet and Bacteroides uniformis, commercially available as probiotics. In conclusion, our study suggests a potential role of individual components of the gut microbiota in the aetiology of VS.

Abstract Background Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology. Materials & Methods We investigated associations of age at menarche and age at menopause, pregnancy‐related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Results During 15 years of follow‐up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs.

Background: Impairment of the blood-brain barrier (BBB) is considered to be a common feature among neurodegenerative diseases, including Alzheimer's, Parkinson's and prion diseases. In prion disease, increased BBB permeability was reported 40 years ago, yet the mechanisms behind the loss of BBB integrity have never been explored. Recently, we showed that reactive astrocytes associated with prion diseases are neurotoxic. The current work examines the potential link between astrocyte reactivity and BBB breakdown. Results: In prion-infected mice, the loss of BBB integrity and aberrant localization of aquaporin 4 (AQP4), a sign of retraction of astrocytic endfeet from blood vessels, were noticeable prior to disease onset. Gaps in cell-to-cell junctions along blood vessels, together with downregulation of Occludin, Claudin-5 and VE-cadherin, which constitute tight and adherens junctions, suggested that loss of BBB integrity is linked with degeneration of vascular endothelial cells. In contrast to cells isolated from non-infected adult mice, endothelial cells originating from prion-infected mice displayed disease-associated changes, including lower levels of Occludin, Claudin-5 and VE-cadherin expression, impaired tight and adherens junctions, and reduced trans-endothelial electrical resistance (TEER). Endothelial cells isolated from non-infected mice, when co-cultured with reactive astrocytes isolated from prion-infected animals or treated with media conditioned by the reactive astrocytes, developed the disease-associated phenotype observed in the endothelial cells from prion-infected mice. Reactive astrocytes were found to produce high levels of secreted IL-6, and treatment of endothelial monolayers originating from non-infected animals with recombinant IL-6 alone reduced their TEER. Remarkably, treatment with extracellular vesicles produced by normal astrocytes partially reversed the disease phenotype of endothelial cells isolated from prion-infected animals. Conclusions: To our knowledge, the current work is the first to illustrate early BBB breakdown in prion disease and to document that reactive astrocytes associated with prion disease are detrimental to BBB integrity. Moreover, our findings suggest that the harmful effects are linked to proinflammatory factors secreted by reactive astrocytes.

Cholesterol-25-hydroxylase (CH25H), the biosynthetic enzyme for 25-hydroxycholesterol (25HC), is most highly expressed in the lung, but its role in lung biology is poorly defined. Recently, we reported that Ch25h is induced in monocyte-derived macrophages recruited to the airspace during resolution of lung inflammation and that 25HC promotes liver X receptor–dependent (LXR-dependent) clearance of apoptotic neutrophils by these cells. Ch25h and 25HC are, however, also robustly induced by lung-resident cells during the early hours of lung inflammation, suggesting additional cellular sources and targets. Here, using Ch25h–/– mice and exogenous 25HC in lung injury models, we provide evidence that 25HC sustains proinflammatory cytokines in the airspace and augments lung injury, at least in part, by inducing LXR-independent endoplasmic reticulum stress and endothelial leak. Suggesting an autocrine effect in endothelium, inhaled LPS upregulates pulmonary endothelial Ch25h, and non-hematopoietic Ch25h deletion is sufficient to confer lung protection. In patients with acute respiratory distress syndrome, airspace 25HC and alveolar macrophage CH25H were associated with markers of microvascular leak, endothelial activation, endoplasmic reticulum stress, inflammation, and clinical severity. Taken together, our findings suggest that 25HC deriving from and acting on different cell types in the lung communicates distinct, temporal LXR-independent and -dependent signals to regulate inflammatory homeostasis.

The medical literature speaks about the influence of the oral cavity environment on the orthodontic archwires containing nickel (Ni) in their structure, causing corrosion of the archwires with the release of nickel ions into the patient’s oral fluids leading to its ingestion. If the nickel content in the body exceeds certain proportions, it is considered hazardous and can cause negative effects on the patient’s body.Aim. To assess whether the clinical application of round thermoactive nickel-titanium (NiTi) archwires will risk increasing the concentration of (Ni) ions in the patient’s oral fluids within first two months of the orthodontic treatment.Materials and methods. The Research was conducted on 17 patients, aged 14 to 27 years, fixed metallic orthodontic appliances were used for treatment. Using an atomic absorption spectrophotometer, oral fluid Samples were analyzed to determine the preliminary рН. Oral fluid samples were gathered from all participants of the study groups during different periods of time, observation was as follows: Before installation of fixed appliances, immediately after fixing the braces and tying up the thermoactive NiTi archwires, in 7 days, one month and two months after fixation.Results. There were no statistically significant differences in concentration of (Ni) ions in first two months of treatment. However, in (25 %) of samples taken from patients in 1-2 months after the beginning of treatment a small increase in concentration of Ni ions (by 7,5 %) was observed.Conclusions. It is improbable that a thermoactive NiTi archwire has a significant additional Ni load for patients undergoing orthodontic treatment.

Lung endothelium resides at the interface between the circulation and the underlying tissue, where it senses biochemical and mechanical properties of both the blood as it flows through the vascular circuit and the vessel wall. The endothelium performs the bidirectional signaling between the blood and tissue compartments that is necessary to maintain homeostasis while physically separating both, facilitating a tightly regulated exchange of water, solutes, cells, and signals. Disruption in endothelial function contributes to vascular disease, which can manifest in discrete vascular locations along the artery-to-capillary-to-vein axis. Although our understanding of mechanisms that contribute to endothelial cell injury and repair in acute and chronic vascular disease have advanced, pathophysiological mechanisms that underlie site-specific vascular disease remain incompletely understood. In an effort to improve the translatability of mechanistic studies of the endothelium, the American Thoracic Society convened a workshop to optimize rigor, reproducibility, and translation of discovery to advance our understanding of endothelial cell function in health and disease. [ABSTRACT FROM AUTHOR]

Truncated phospholipid oxidation products (Tr-OxPL) increase in blood circulation with aging; however, their role in the severity of vascular dysfunction and bacterial lung injury in aging groups remains poorly understood. We investigated the effects of six Tr-OxPL species: KOdiA-PC, POVPC, PONPC, PGPC, Paz-PC, and Lyso-PC on endothelial dysfunction and lung inflammation caused by heat-killed Staphylococcus aureus (HKSA) in young (aged 2–4 months) and old (aged 12–18 months) mice, organotypic culture of precisely cut lung slices, and endothelial cells (mLEC) isolated from young and old mice. HKSA and Tr-OxPL combination caused a higher degree of vascular leak, the accumulation of inflammatory cells and protein in bronchoalveolar lavage, and inflammatory gene expression in old mice lungs. HKSA caused a greater magnitude of inflammatory gene activation in cell and ex vivo cultures from old mice, which was further augmented by Tr-OxPLs. L37pA peptide targeting CD36 receptor attenuated Tr-OxPL-induced endothelial cell permeability in young and old mLEC and ameliorated KOdiA-PC-induced vascular leak and lung inflammation in vivo. Finally, CD36 knockout mice showed better resistance to KOdiA-PC-induced lung injury in both age groups. These results demonstrate the aging-dependent vulnerability of pulmonary vasculature to elevated Tr-OxPL, which exacerbates bacterial lung injury. CD36 inhibition is a promising therapeutic approach for improving pneumonia outcomes in aging population.

Abstract Traumatic brain injury (TBI) has been associated with the development of indirect acute respiratory distress syndrome (ARDS). However, the causative relationship between TBI and lung injury remains unclear. To explore potential mechanisms linking TBI with the development of ARDS, we characterized the effects of serum factors released following TBI and hemorrhagic shock (HS) in a rat model on the pulmonary endothelial cell (EC) barrier dysfunction, a key feature of ARDS. We found that serum samples from animals exposed to both controlled cortical impact (CCI) and HS, but not from sham‐operated rats induced significant barrier dysfunction in human pulmonary artery EC monolayers at 2 days post injury. Thrombin inhibitor and thrombin receptor antagonist attenuated the acute phase of the serum‐induced trans‐endothelial resistance (TER) decline caused by CCI‐HS serum, but not in later time points. However, both the early and late phases of CCI‐HS‐induced EC permeability were inhibited by heparin. The barrier disruptive effects of CCI‐HS serum were also prevented by serum preincubation with heparin‐sepharose. Pulmonary EC treated for 3 h with serum from CCI‐HS rats demonstrated a significant decline in expression of EC junctional protein, VE‐Cadherin, and disassembly of peripheral EC adherens junction complexes monitored by immunostaining with VE‐cadherin antibody. These results suggest that exposure to CCI‐HS causes early and late‐phase barrier disruptive effects in vascular endothelium. While thrombin‐PAR1 signaling has been identified as a mechanism of acute EC permeability increase by CCI‐HS serum, the factor(s) defining long‐term EC barrier disruption in CCI‐HS model remains to be determined.

INTRODUCTION. Coronary artery bypass surgery is the most popular method of surgical treatment of patients with chronic heart failure of ischemic origin. Modern direction of developing the cardiac surgery in treating patients with chronic heart failure of ischemic origin is «off-pump» techniques. However, the high risk of emergency conversion to«on pump» reduce the availability for using «off pump» techniques with this kind of patients. Preoperative risk factors for unplanned conversion to cardiopulmonary bypass have not been studied.The OBJECTIVE was to determine preoperative risk factors of urgent conversion to bypass in patients with congestive ischemic heart failure during off-pump coronary artery bypass grafting.METHODS AND MATERIALS. The results of 44 coronary artery bypass grafting (CABG) off-pump procedures in patients with ischemic cardiomyopathy were retrospectively analyzed. Emergent conversion to artificial circulation was needed due to acute heart failure in 8 (18 %) patients. All patients were divided into 2 groups depending on the necessity for emergency using the cardiopulmonary bypass. Then the patients’ preoperative status was analyzed.RESULTS. We determined that the risk factors of emergent conversion to cardiopulmonary bypass were observed in the following cases: patients after 70 years old with a combined left main coronary artery lesion and right coronary artery occlusion; left ventricle end-diastolic size more than 70 mm; mild mitral insufficiency; the presence of atrial or ventricle rhythm disturbances; EuroSCORE logistic score more than 4.9 %.CONCLUSION. The identified risk factors allow to minimize the risk of urgent conversion to bypass circulation during off-pump myocardial revascularization in patients with congestive ischemic heart failure. When these risk factors are present, it is recommended to use on-pump or on-pump beating heart techniques of coronary artery bypass grafting in these patients.

The most important result of the effect of interparticle interactions of ferromagnetic particles in suspensions is the formation of aggregates and modification of their physical properties, which allows changing the kinetics of separation processes. The interest of the authors to this problem is dictated by both its theoretical content and purely applied aspects within mineral processing. Based on the block-structural approach to technological equipment modeling within the framework of the ideal mixing model, a mathematical model of processes occurring in the working volumes of apparatuses using magnetic forces to intensify the separation of mineral suspensions was created. The use of the MATHCAD software has allowed obtaining analytical solutions of the differential equations system of the model and predictions of the kinetics of aggregation of ferromagnetic particles and physical properties of the formed aggregates, such as coarseness, density, deposition velocity in the gravity field as functions of medium parameters and external magnetic fields. The analytical solutions are necessary for developing simulation models of magnetic separation processes in strong, weak, uniform and non-uniform magnetic fields, magnetic deslammers and filters.

Orthodontic treatment planning is a practice that depends on the accuracy of teeth and dental arches’ size measurement. The purpose of the study is to compare the accuracy and the duration of teeth and dental arches’ measurement, utilizing different approaches from conventional plaster models to virtual 3D models obtained by intraoral and extraoral scanners. Fifteen patients were included in the study (7 males, 8 females, mean age 21.7 ± 0.7 years), with a moderate anterior teeth crowding and class I Angle’s classification of malocclusion. Plaster models, as well as virtual 3D scans were obtained by intraoral and extraoral scanners prior to the orthodontic treatment, crown sizes of incisors, transverse and longitudinal sizes of dentitions, as well as the length of dental arches’ segments were measured, the duration of each measurement was also evaluated. Material and Methods: groups were allocated according to the four different ways the measurements were obtained: 1) biometric measurements on plaster models of the jaws; 2) virtual 3D data of the dentition using intraoral scanner; 3) 3D scanning data of plaster models; 4) 3D scanning data of silicone impressions. Results: The differences between the same type of measurements using a 3D scanner and measurements on plaster models when compared to the same control points in the oral cavity were, on average, 0.3 ± 0.01 mm. The time required to work with plaster models compared to the time taken to obtain virtual models on a 3D scanner was significantly greater, respectively, 15.3 ± 0.7 min. and 5.1 ± 0.2 min. Thus, 3D scanning is the most accurate standardized method for assessing the size of teeth and dental arches with shorter duration of manipulations, although it requires laboratory equipment and certain manual skills.

RationalePhosPhatidic Acid Phosphatase type 2B (PPAP2B), an integral membrane protein known as lipid phosphate phosphatase (LPP3) that inactivates lysophosphatidic acid, was implicated in coronary artery disease (CAD) by genome-wide association studies. However, it is unclear whether genome-wide association studies-identified coronary artery disease genes, including PPAP2B, participate in mechanotransduction mechanisms by which vascular endothelia respond to local atherorelevant hemodynamics that contribute to the regional nature of atherosclerosis.ObjectiveTo establish the critical role of PPAP2B in endothelial responses to hemodynamics.Methods and resultsReduced PPAP2B was detected in vivo in mouse and swine aortic arch (AA) endothelia exposed to chronic disturbed flow, and in mouse carotid artery endothelia subjected to surgically induced acute disturbed flow. In humans, PPAP2B was reduced in the downstream part of carotid plaques where low shear stress prevails. In culture, reduced PPAP2B was measured in human aortic endothelial cells under atherosusceptible waveform mimicking flow in human carotid sinus. Flow-sensitive microRNA-92a and transcription factor KLF2 were identified as upstream inhibitor and activator of endothelial PPAP2B, respectively. PPAP2B suppression abrogated atheroprotection of unidirectional flow; inhibition of lysophosphatidic acid receptor 1 restored the flow-dependent, anti-inflammatory phenotype in PPAP2B-deficient cells. PPAP2B inhibition resulted in myosin light-chain phosphorylation and intercellular gaps, which were abolished by lysophosphatidic acid receptor 1/2 inhibition. Expression quantitative trait locus mapping demonstrated PPAP2B coronary artery disease risk allele is not linked to PPAP2B expression in various human tissues but significantly associated with reduced PPAP2B in human aortic endothelial cells.ConclusionsAtherorelevant flows dynamically modulate endothelial PPAP2B expression through miR-92a and KLF2. Mechanosensitive PPAP2B plays a critical role in promoting anti-inflammatory phenotype and maintaining vascular integrity of endothelial monolayer under atheroprotective flow.