Indirect Action Research Articles

Analysis of Oxidative Stress Markers in Plasma Derived from Individuals Exposed to Ionizing Radiation

Ionizing radiation with low-linear energy transfer generates reactive oxygen species (ROS) or free radicals such as superoxide, hydrogen peroxide, and hydroxyl radicals by indirect action of energy on water molecules and simultaneously generating doublestrand breaks (DSBs), which are known to be lethal, by direct action on DNA itself, with sequence apoptosis or stress-related responses [1,2].

Enterprise functioning quality management under conditions of destructive program actions

The trends of development of modern enterprises lead to building network-connected territorially dispersed structures, which determine the enhanced requirements to control systems. Therefore, the control systems are compelled to use general technological resource — cyber-domain, which is the reason for transition of competitive confrontation to technological sphere and leads to the emergence of premeditated direct or indirect destructive program actions as one of the most efficient facilities for getting competitive advantage. The enterprise functioning quality control under new conditions requires provision of a subsystem of taking decisions with timely, authentic and complete information on the state of cyber-domain. The task of getting such information can be realized using modeling methods. The analysis of the existing modeling methods of communication networks has demonstrated availability of an essential deficiency — absence of keeping record of destructive program actions with simultaneous functioning of two conflicting enterprise control systems at the unified technological resource. The article describes a new method of simulating communication networks rectifying the revealed deficiency. The presented method can make a basis of the model, which is capable to enhance information awareness of the subsystem of taking decisions on the state of a simulated network, enhancing by the same the quality of enterprise control and, accordingly, the quality of functioning of the enterprise proper. The article is the development of the method of simulating of premeditated damages of elements of communication network patented by the authors.

New thiazolidinones reduce iron overload in mouse models of hereditary hemochromatosis and β-thalassemia.

Genetic iron-overload disorders, mainly hereditary hemochromatosis and untransfused β-thalassemia, affect a large population worldwide. The primary etiology of iron overload in these diseases is insufficient production of hepcidin by the liver, leading to excessive intestinal iron absorption and iron efflux from macrophages. Hepcidin agonists would therefore be expected to ameliorate iron overload in hereditary hemochromatosis and β-thalassemia. In the current study, we screened our synthetic library of 210 thiazolidinone compounds and identified three thiazolidinone compounds, 93, 156 and 165, which stimulated hepatic hepcidin production. In a hemochromatosis mouse model with hemochromatosis deficiency, the three compounds prevented the development of iron overload and elicited iron redistribution from the liver to the spleen. Moreover, these compounds also greatly ameliorated iron overload and mitigated ineffective erythropoiesis in β-thalassemic mice. Compounds 93, 156 and 165 acted by promoting SMAD1/5/8 signaling through differentially repressing ERK1/2 phosphorylation and decreasing transmembrane protease serine 6 activity. Additionally, compounds 93, 156 and 165 targeted erythroid regulators to strengthen hepcidin expression. Therefore, our hepcidin agonists induced hepcidin expression synergistically through a direct action on hepatocytes via SMAD1/5/8 signaling and an indirect action via eythroid cells. By increasing hepcidin production, thiazolidinone compounds may provide a useful alternative for the treatment of iron-overload disorders.

Непрямые действия агентов и авторитетные отношения в STIT и PDL

Непрямые действия агентов и авторитетные отношения в STIT и PDL

Elucidation of molecular expression associated with abnormal development and sterility caused by electron beam irradiation in Spodoptera litura (F.) (Lepidoptera: Noctuidae)

Purpose: The objective of the present study was to elucidate the mode of indirect action of electron beam irradiation at the molecular level against a quarantine pest, Spodoptera litura (F.).Material and methods: Electron beam irradiation (50–200 Gy) was applied to S. litura eggs, larvae, pupae, and adults, after which the feeding area, body weight, deformity of pupae and adults, ovarian development, expression levels of vitellogenin (Vg) and vitellogenin receptor (VgR) genes, and protein levels were analyzed.Results: The amount of feeding by S. litura larvae and the synthesis level of 70 kDa storage protein significantly decreased as the electron beam dose increased. When larvae were treated with the electron beam, morphological deformities appeared in the pupae, and abnormal wing disc (AWD) expression significantly decreased. Ovarian development was completely inhibited in emerged adults that had undergone 200 Gy electron beam irradiation as pupae. Quantitative real-time PCR (qRT-PCR) assays showed significant downregulation of the Vg and VgR genes due to electron beam irradiation; whereas the synthesis level of Vg protein (190 kDa) did not decrease with time in eggs unlike in non-irradiated (control) S. litura eggs, exhibiting irradiation induced impairment of Vg functioning.Conclusions: These findings of radiation-induced abnormal development and sterility in S. litura together with the correlated changes at the molecular level may facilitate the development of a phytosanitary strategy against this quarantine pest using electron beam irradiation.

Computational strategy for studying structural change of tritium-substituted macromolecules by a beta decay to helium-3

We propose a computational strategy for investigating structural change of tritium-substituted macromolecules. Effects of radiation on macromolecules such as polymeric materials and DNA are classified into three categories: (1) direct action, (2) indirect action, and (3) decay effect. In this study, we focus on the decay effect exclusively. After a beta decay of substituted tritium in macromolecules to helium-3, the generated inert helium-3 is assumed to be deleted quickly. To get an insight into the decay effect to the damage of macromolecules, we perform molecular dynamics simulations of tritium-deleted macromolecules and analyze their structural change. Preliminary simulation results of decay effect on polymeric materials and DNA are presented.

Acute Infectious Diarrhea.

Acute infectious diarrhea (AID) is one of the most common diseases in pediatric age with relevant burden both in high- and in low-income countries.Thanks to their direct action on enterocyte functions and indirect actions on mucosal and systemic immune system and intestinal microenvironment, probiotics are an ideal intervention to manage AID in childhood. However, their efficacy is strictly related to strains and indications, and practitioners should take this information into account in clinical practice.This chapter summarizes the main mechanisms of action of probiotics in AID, with a focus on proof of efficacy supporting their use in prevention and treatment of infant AID.The use of selected strains in appropriate doses is strongly recommended by guidelines of AID, based on large and consistent proofs of efficacy and safety. At present, therapy with probiotics of AID is arguably the strongest indication for probiotics in medicine. Future research should investigate probiotic efficacy in at-risk populations and settings where the evidence is missing.Their role in prevention of AID is however questionable in healthy population, whereas it should be considered in at-risk population. Evidence for prevention of diarrhea in day-care centers and communities is lacking, but consistent evidence supports efficacy in prevention of hospital acquired diarrhea.Overall, AID is the most convincing area for probiotic use in children, and effective strains should be used early after onset of symptoms.

Modeling and Investigation of the Process of Hot Rolling of Large-Sized Ingots from Aluminum Alloy of the Al-Mg System, Economically Alloyed by Scandium

Results of researches of process of hot rolling of ingots from the experimental aluminum alloy which is economically alloyed by scandium are given. The computer model of process of hot rolling with the use of which the straining, temperature and speed processing modes conditions is calculated and also power parameters of processing is calculated in applied to industrial conditions. It is shown that the use in the model of a certain shape of the ingot faces (Petrov's lock) and indirect rolling action in the edging stand is made it possible to reduce the likelihood of the formation and further development of micro cracks on the edges of rolled metal. The adequacy of results of modeling was confirmed by carrying out pilot-industrial tests when rolling large-size ingots from the experimental alloy and obtaining batches of hot-rolled plates and sheets of various sizes. The tensile test was used to study deformed samples after rolling and samples obtained on five regimes of heat treatment with varying heating temperatures of 300, 350 and 380 oС and holding time in the furnace for 1 and 3 hours. The results of the studies on samples of hot-rolled sheets 10 mm thick showed that, compared with the initial state, the strength characteristics of the metal after heat treatment are reduced by an average of 12-20%, and plastic characteristics increase by 50-65%. In this case, the heat treatment regimes 1 - 3 give a good ratio of the ductility and plastic properties of the metal.

Discursos médicos disciplinadores y experiencias emocionales de aborto farmacológico de mujeres en Cuyo, Argentina.

Objectives The aim of this article is to recognize and understand how certain discourses and practices carried out by health professionals and sonographers shape the emotional experiences of women who aborted with medication in two provinces of Cuyo, Argentina. Method The research was carried out with a qualitative design through a biographical method and thematic life-stories that emphasize the experience with medical abortion in conditions where abortion is legally and socially restricted. For this research, 18 in-depth interviews were conducted and analysed with women who underwent at least one voluntary pharmacological abortion made in a clandestine way between 2010 and 2019 and who registered interactions with professionals. The interviews were conducted between 2016 and 2019. Results Criminalizing, disciplinary and/or normativizing discourses implemented through direct and indirect actions affected the configuration of women's emotional experiences. The emotional effects of clandestinity were reinforced: they intensified the fear for their own lives and the fear of being denounced and imprisoned; promoted feelings of vulnerability, uncertainty, lack of control over one’s life, persecution and imposed certain silences. Conversely, moralizing and blaming discourses did not have said effects on the women interviewed. Conclusions These interventions are strategies of gender discipline that produce and reproduce criminalizing power practices and that have a central role in the experiences of women: said discourses affect negatively their emotional health; they push them to take avoidable risks and they violently limit their right to an integral health. Nonetheless, they do not take away women’s power to make decisions about their own body.

Fences in the borderland: technique, landscape and the architectures of domestication in the Brazilian-Uruguayan Pampa

Abstract Recent perspectives on domestication have emphasized the importance of technical objects and other environmental elements as mediators of the relations between humans, animals and the many landscapes they inhabit. Using the concept of “architecture of domestication”, proposed by Anderson and others (2017), this article investigates the role of alambrados (wire and wooden fences) in the context of animal husbandry in the Brazilian-Uruguayan Pampa, the technical processes involved in their construction, as well as the new configurations and uses for these structures that have emerged along with the biological invasion of European wild boars (Sus scrofa) in the region. I will show that the alambrados are key elements in the difference between positive direct action and negative indirect action in relation to the animals of the herd within the Pampeano system of domestication.

Development and evaluation of a remotely controlled and monitored self-propelled sprayer in tomato crops

The tomato is one of the main crops in Brazil. In large-scale cultivation, pesticides are applied to the plant to prevent the direct or indirect action of animal or vegetable life, aiming at higher productivity and better quality fruit. However, the products, if used incorrectly, may affect the health of workers involved in the activity. A prototype of a self-propelled sprayer, remotely controlled and monitored via radio signals, was therefore developed to be used in tomato crops, thus minimising worker contact with the chemical substances used when spraying. The basic prototype comprises an agricultural mini-tractor, a motorised pneumatic sprayer (atomiser) and a set of electronic and mechanical sensors and actuators, which allow the assembly to be controlled remotely and images captured by a video camera to be viewed on a tablet. After development, the principal dimension, weight and operational characteristics of the prototype were identified; the prototype was also used for spraying ten tomato plants in the crop, with seven different points being observed for each plant. The results were analysed statistically, giving the following coefficients of variation: 15.13% for spray coverage, 18.70% for droplet density and 16.68% for product deposition on the folioles. Based on these values, it was concluded that the development of a remotely controlled and monitored self-propelled sprayer prototype, and its use in spraying tomato crops, were viable.

CASE OF ACQUIRED COAGULOPATHY

In recent years, the number of patients receiving anticoagulant therapy worldwide is growing rapidly. This is due to the rapidly expanding scope of their application: an increasing number of patients with non-valvular heart disease, including atrial fibrillation, the risk of thromboembolic events, an increase in the number of surgical interventions, especially in cardiac surgery (in the treatment of valvular heart disease, cardiac anomalies, infective endocarditis, staging of heart pacemakers, conducting electric cardioversion), the use of anticoagulants in the treatment of other organs and systems (in neurology, angiosurgery, obstetrics and gynecology). Despite the presence of a large number of anticoagulants in the arsenal of the modern physician, one of the most studied and often prescribed is varfarin. Warfarin is an anticoagulant of the indirect action of the coumarin group, a competitive antagonist of vitamin K. However, along with high availability and efficiency of its use, it has a large number of possible contraindications and features of the reception, such as: many drug-drug and other interactions, the need for careful control of the dosage and the regimen of the drug, strict control of the international normalized ratio throughout therapy. With caution, this drug should be used in patients who abuse alcohol and have cognitive impairment. In this group of patients, in addition to personal awareness of patients, it is necessary to conduct explanatory conversations with relatives / caregivers about all possible side effects and measures for their prevention. Non-observance of precautionary measures at therapy by warfarin can lead to heavy, and in rare instances even lethal consequences, one of which is warfarin-induced coagulopathy. This clinical case presents a case of the development of severe acquired (warfarin-induced) coagulopathy in a patient with cognitive dysfunction.

Antioxidant and Anti-Inflammatory Effects of Delphinidin on Glial Cells and Lack of Effect on Secretase Enzyme

Beneficial health effects of anthocyanin extracts such as antioxidation and anti-inflammatory effects have been demonstrated in many studies. However, studies focusing on these effects exerted specifically by delphinidin (anthocyanin extract) are generally poor. The purpose of this study was to explore the in vitro protective functional role of anthocyanin extract, delphinidin, on oxidation- and inflammation-induced injury in C6 neuroglial cells, and to examine its effect on suppression of secretase enzyme, a key factor in Alzheimer’s disease development. Cytotoxicity assay results revealed that delphinidin at high concentrations enhanced cell viability of spiked cells. Moreover, in a dose-dependent manner, delphinidin caused glutathione levels to increase in cells, a critical indicator of the cellular redox state, versus cells treated with hydrogen peroxide. Delphinidin decreased the expression of MCP-1 and CINC-1, two major cytokines markers in inflammatory situations versus tumor necrosis factor-α-induced damage. However, delphinidin, even at higher concentrations, did not suppress the secretase enzyme activity, indicating its indirect action in ameliorating the underlying cause of the disease. Our findings suggested that delphinidin could be a promising candidate for the development of therapeutics for the management of diseases associated with oxidative stress and inflammatory expressions such as neurodegenerative diseases.

The NMDA receptor intracellular C-terminal domains reciprocally interact with allosteric modulators

N-methyl-d-aspartate receptors (NMDARs) have multiple prominent roles in CNS function but their excessive or insufficient activity contributes to neuropathological/psychiatric disorders. Consequently, a variety of positive and negative allosteric modulators (PAMs and NAMs, respectively) have recently been developed. Although these modulators bind to extracellular domains, in the present report we find that the NMDAR’s intracellular C-terminal domains (CTDs) significantly influence PAM/NAM activity. GluN2 CTD deletion robustly affected NAM and PAM activity with both enhancing and inhibiting effects that were compound-specific and NMDAR subunit-specific. In three cases, individual PAMs became NAMs at specific GluN2-truncated receptors. In contrast to GluN2, GluN1 CTD removal only reduced PAM activity of UBP684 and CIQ, and did not affect NAM activity. Consistent with these findings, agents altering phosphorylation state or intracellular calcium levels displayed receptor-specific and compound-specific effects on PAM activity. It is possible that the GluN2′s M4 domain transmits intracellular modulatory signals from the CTD to the M1/M4 channel gating machinery and that this site is a point of convergence in the direct or indirect actions of several PAMs/NAMs thus rendering them sensitive to CTD status. Thus, allosteric modulators are likely to have a marked and varied sensitivity to post-translational modifications, protein-protein associations, and intracellular ions. The interaction between PAM activity and NMDAR CTDs appears reciprocal. GluN1 CTD-deletion eliminated UBP684, but not pregnenolone sulfate (PS), PAM activity. And, in the absence of agonists, UBP684, but not PS, was able to promote movement of fluorescently-tagged GluN1-CTDs. Thus, it may be possible to pharmacologically target NMDAR metabotropic activity in the absence of channel activation.

Theory of mind and peer cooperation in two play contexts

We examined the associations between theory of mind (ToM) and peer cooperation among preschoolers in two play contexts. Fifty-eight 3-to-5-year-old children from middle class suburbs of Brisbane, Australia were tested for ToM and observed in same-age and same-gender dyads for peer cooperation. To measure ToM, we administered the 5-step ToM scale. With an implicit false belief task, children's eye gaze responses to indirect action anticipation prompt were assessed. To measure peer cooperation, we used independent and joint play contexts and coded communicative and coordinated behaviours. Performance on the ToM scale, but not implicit false belief, was associated with peer cooperation in the independent play, but not the joint play context. Dyadic data analysis showed that in the independent play context, ToM played a critical role for cooperation, both as an actor and a partner. These results support recommendations for ToM training in early childhood to support children's cooperative behaviours.

Degradation of antibiotics and antibiotic resistance genes in fermentation residues by ionizing radiation: A new insight into a sustainable management of antibiotic fermentative residuals

Antibiotic fermentative residues are categorized into hazardous wastes in China due to the existence of antibiotic resistance genes (ARGs) and residual antibiotics How to treat and manage these wastes is a new challenge. This paper investigated the treatment of erythromycin thiocyanate fermentation (EryTcF) residues using ionizing radiation technology for removing ARGs and antibiotics from the fermentation residues. The results showed that as exposed the EryTcF residues to gamma radiation, the abundance of four macrolide resistance genes (ereA, ermB, mefA and mpfB) decreased 1.0–1.3 log with 90–95% removal, and around 56% of erythromycin was removed at absorbed dose of 30 kGy and room temperature (19–22 °C). Direct action of γ-ray radiation contributed to 42–53% of ARGs removal and indirect action (radicals' reaction) was mainly responsible for erythromycin removal (84%). The positive correlation between total ARGs and Shannon index was observed. The potential ARGs-linked hosts were assigned to genera Aeromonas and Enterobacteriaceae and their abundance decreased by 36–43% at 30 kGy. Radiation has not obvious influence on the nutrient components of residues, such as protein content, suggesting that the radiation treated fermentative residues can be used as fertilizer, which is favorable for the development of recycling economy in antibiotic pharmaceutical factory. The results could provide a new insight into a sustainable management of antibiotic fermentative residuals.

Robotic Technology in Orthopaedic Surgery.

* Robotic technology used in orthopaedics can be classified on the basis of direct and indirect action and according to the mechanism of cutting, including autonomous, haptic, and boundary control.* Robotics have been used in multiple orthopaedic subspecialties including spine, total joint arthroplasty, trauma, shoulder, and foot and ankle.* Advantages of using robotic technology in orthopaedics include the possibility of improving implant placement (e.g., reducing outliers), accessing certain anatomic areas, reducing complications, decreasing fluoroscopy use, and performing remote surgery.* Disadvantages of using robotics in orthopaedics include increased costs, the need for updated software, the surgeon learning curve and increased operative time, imaging for preoperative templating, potential incorrect placement of implants with poor input of data from the surgeon, and possibly no difference in long-term outcomes.

Active full-length DNA A\u03b242 immunization in 3xTg-AD mice reduces not only amyloid deposition but also tau pathology

BackgroundAlzheimer’s disease (AD) is the most well-known and most common type of age-related dementia. Amyloid deposition and hyperphosphorylation of tau protein are both pathological hallmarks of AD. Using a triple-transgenic mouse model (3xTg-AD) that develops plaques and tangles in the brain similar to human AD, we provide evidence that active full-length DNA amyloid-β peptide 1–42 (Aβ42) trimer immunization leads to reduction of both amyloid and tau aggregation and accumulation.MethodsImmune responses were monitored by enzyme-linked immunosorbent assay (ELISA) (antibody production) and enzyme-linked immunospot (cellular activation, cytokine production). Brains from 20-month-old 3x Tg-AD mice that had received DNA Aβ42 immunotherapy were compared with brains from age- and gender-matched transgenic Aβ42 peptide-immunized and control mice by histology, Western blot analysis, and ELISA. Protein kinase activation and kinase levels were studied in Western blots from mouse hemibrain lysates.ResultsQuantitative ELISA showed a 40% reduction of Aβ42 peptide and a 25–50% reduction of total tau and different phosphorylated tau molecules in the DNA Aβ42 trimer-immunized 3xTg-AD mice compared with nonimmunized 3xTg-AD control animals. Plaque and Aβ peptide reductions in the brain were due to the anti-Aβ antibodies generated following the immunizations. Reductions of tau were likely due to indirect actions such as less Aβ in the brain resulting in less tau kinase activation.ConclusionsThe significance of these findings is that DNA Aβ42 trimer immunotherapy targets two major pathologies in AD—amyloid plaques and neurofibrillary tangles—in one vaccine without inducing inflammatory T-cell responses, which carry the danger of autoimmune inflammation, as found in a clinical trial using active Aβ42 peptide immunization in patients with AD (AN1792).

Methylhexaneamine causes tachycardia and pressor responses indirectly by releasing noradrenaline in the rat

We have investigated the mode of cardiovascular action of the stimulant methylhexaneamine (MHA) in terms of direct or indirect adrenergic actions in anaesthetised rats. Male and female rats were anaesthetised with pentobarbitone and pressor (changes in diastolic blood pressure) and cardioaccelerator responses to MHA were examined in vehicle treated or chemically sympathectomised rats. MHA produced pressor and cardioaccelerator responses over the same dose range in vehicle treated animals, with significant cardioaccelerator and pressor responses occurring at MHA (0.1 mg/kg). However, tachycardia was more marked than pressor responses. In sympathectomised rats, cardiac and pressor actions of MHA were greatly attenuated. MHA was also studied in isolated tissues. In rat vas deferens, MHA produced small tonic contractions, but these were virtually abolished by sympathectomy In rat aorta, MHA produced almost no contractions. These results are also consistent with largely indirect actions. There were no differences between male and female rats. It is concluded that MHA acts predominantly indirectly in both male and female rats causing noradrenaline release to produce cardiovascular actions and that as a result pressor and cardiac responses occur at similar doses. This propensity for MHA to cause tachycardia and rises in blood pressure at similar doses range may have implications for adverse cardiovascular actions.

Glucagon-like peptide-1 receptor agonists and cardiovascular protection in type 2 diabetes: a pathophysiology-based review of clinical implications.

Cardiovascular outcome trials (CVOT) with glucagon-like peptide-1 receptor agonists (GLP-1 RA) have had variable results to date: with two CVOTs being positive and two concluding neutrality/safety results for primary cardiovascular outcome. Mechanistic insights delving into the pathophysiologic mechanisms that may link certain GLP-1 RA to cardioprotection may help define the application of this medication class in clinical practice based on the evidence of the CVOT data. We discuss the various mechanisms that have been postulated from animal and preclinical human studies to help explain the benefits observed in CVOTs with GLP-1 RA. Cardiovascular benefits of GLP-1 may be dependent on the complex interactions of this incretin hormone with the atherosclerotic pathways, either through its direct actions on the cardiovascular system or indirectly through intermediary actions on metabolism, energy transfer, inflammation or thrombosis. An indirect metabolic action of GLP-1 RA, via an initial step of achieving glucose homeostasis or balancing inter-organ energy metabolism, leading to favorable downstream effects on the inflammation-thrombosis pathways, finally impacting atherosclerosis, appears compelling. In addition to their metabolic benefits, specific GLP-1 RA medications offer cardiovascular protection in high-risk type 2 diabetes. Further mechanistic studies and clinical trials in lower cardiovascular risk populations may help cement the place of this class of medications across the spectrum of type 2 diabetes.