Recycling of epidermal growth factor-receptor complexes in A431 cells: identification of dual pathways

The intracellular sorting of EGF-receptor complexes (EGF-RC) has been studied in human epidermoid carcinoma A431 cells. Recycling of EGF was found to occur rapidly after internalization at 37 degrees C. The initial rate of EGF recycling was reduced at 18 degrees C. A significant pool of internalized EGF was incapable of recycling at 18 degrees C but began to recycle when cells were warmed to 37 degrees C. The relative rate of EGF outflow at 37 degrees C from cells exposed to an 18 degrees C temperature block was slower (t1/2 approximately 20 min) than the rate from cells not exposed to a temperature block (t1/2 approximately 5-7 min). These data suggest that there might be both short- and long-time cycles of EGF recycling in A431 cells. Examination of the intracellular EGF-RC dissociation and dynamics of short- and long-time recycling indicated that EGF recycled as EGF-RC. Moreover, EGF receptors that were covalently labeled with a photoactivatable derivative of 125I-EGF recycled via the long-time pathway at a rate similar to that of 125I-EGF. Since EGF-RC degradation was also blocked at 18 degrees C, we propose that sorting to the lysosomal and long-time recycling pathway may occur after a highly temperature-sensitive step, presumably in the late endosomes

Percolation in Models of Thin Film Depositions

We have studied the percolation behaviour of deposits for different (2+1)-dimensional models of surface layer formation. The mixed model of deposition was used, where particles were deposited selectively according to the random (RD) and ballistic (BD) deposition rules. In the mixed one-component models with deposition of only conducting particles, the mean height of the percolation layer (measured in monolayers) grows continuously from 0.89832 for the pure RD model to 2.605 for the pure RD model, but the percolation transition belong to the same universality class, as in the 2- dimensional random percolation problem. In two- component models with deposition of conducting and isolating particles, the percolation layer height approaches infinity as concentration of the isolating particles becomes higher than some critical value. The crossover from 2d to 3d percolation was observed with increase of the percolation layer height.Comment: 4 pages, 5 figure

Features of diagnostics of gastroesophageal and duodenogastric reflux in patients with complicated forms of peptic ulcer.

Purpose – to improve the results of surgical treatment of duodenal ulcer due to preoperative diagnosis of concomitant reflux disease and its correction. Before surgery, 46 patients with complicated forms of peptic  ulcer disease underwent pH monitoring and 23 – impedance-pH monitoring. Pathological gastroesophageal reflux was found in 58 cases. Before surgery, esophageal pH monitoring was performed in 46 patients with complicated forms of peptic ulcer disease. Against the background of hyper – and normacidity of the stomach in 39 patients pathological acidic gastroesophageal reflux disease with a significant increase of De Meester index was confirmed. Impedance-pH monitoring was performed before surgery in 23 patients with complicated forms of peptic ulcer and concomitant gastroesophageal reflux. Erosive form of gastroesophageal reflux disease was confirmed endoscopically in all patients with hyperacidity (17) and normal acidity (6) of the stomach. In 19 cases pathological gastroesophageal reflux disease was found. In 13 cases the cause of disorders in anti-reflux barrier was a diaphragmatic hernia of I-II degree. Gastroesophageal reflux disease was caused by increased intragastric pressure due to ulcer stenosis in 6 patients. pH- monitoring in patients with acidic gastroesophageal reflux allows to establish a pathological or physiological reflux. Conducting impedance-pH monitoring allows to determine the number of reflux episodes and their qualitative characteristics (acidic or alkaline; liquid, gas or mixed), as well as to determine the indications for a differentiated approach in the treatment of gastroesophageal reflux

Patient routing and process approach implementation for regional oncology service

Background. Cancer care involves a multidisciplinary approach to diagnosis and treatment of patients. A complex interaction of actors in the deployment of oncology services dictates usage of modern management technologies for improving the quality and efficiency of patient care through processes optimisation.Objectives. Provision of recommendations for patient routing based on research into the oncology service inter-level information exchange, integration of the process approach and electronic services. The lack of a unified information space with a regional oncology service has been explained. Measures are proposed for the patient routing optimisation as part of establishing a unified digital oncology service circuit.Methods. The oncology service was effectively remodelled through functional and information engineering of electronic services and the process management integration to establish a horizontal decision flow between facilities and employees on a process level bypassing the supervisor coordination. Statistical approaches were used to analyse the oncological patient population.Results. The following electronic services have been implemented: specialised patient referral routing, telemedicine and teleradiology. A comprehensive information framework has been created comprising medical, laboratory and radiological information subsystems integrated through regional electronic services of the unified state healthcare information platform. The goals, objectives, general principles, architecture and expected social economic impact on healthcare of Krasnodar Krai have been defined.Conclusion. Use of electronic services ensures an improved quality of specialised care and effective routing of patients. We perceive prospects of the integrated information platform in the extension and improvement of its subsystems’ functionality and content, sourcing more data providers and the circuit expansion to the federal and regional levels

Ce-doped Li6Ln(BO3)3 (Ln = Y, Gd) Single crystals fibers grown by micro-pulling down method and luminescence properties

Ce3+-doped borate crystal fibers of Li6Gd(BO 3)3 (LGBO) and Li6Y(BO3)3 (LYBO) compositions are grown by the micro-pulling down (μ-PD) method for potential application in developing new neutron detectors. The ternary equilibrium diagram of Li2O-Gd2O3-B 2O3 is drawn and the preparations of homogeneous mixed LGBO and LYBO powders and growth conditions for single crystal fibers are discussed. Absorption, excitation and X-ray luminescence spectra are investigated. Absolute light yield derived from energy spectra and kinetic decay curves measured under α- and γ-scintillations of Ce 3+-doped LGBO and LYBO single crystal fibers is provided. © 2012 Elsevier B.V. All rights reserved

Limitations and opportunities of cancer treatment in the COVID-19 pandemic

The COVID-19 pandemic has affected all medical fields and brought up a lot of serious problems. The features of the COVID-19 infection in patients with cancer are important to understand. According to many articles, patients with cancer are more vulnerable to COVID-19 infection. Patients undergoing anticancer treatment have 1-4% morbidity rate. Patients with hematological diseases and lung cancer are at higher risk of SARS-CoV-2 infection and also have more severe symptoms and complications. In this article we discuss the effect of the tumors on the immune system and comprehend the pathogenesis of the coronavirus disease according to its impact on the immunity. Moreover, in the review we analyze available data about the influence of the different types of cancer therapy (chemotherapy, target therapy, radiotherapy and immunotherapy) on the severity of the COVID-19 infection. Evidence on the effect of chemotherapy on severity and mortality from COVID-19 is contradictory. Whereas there are some authors concluding that chemotherapy treatment is not affecting the severity of COVID-19 disease, there are also some works where the connection between these facts was established. At the same time target therapy, radio- and immunotherapy most likely do not worsen the SARS-CoV-2 infection and are not associated with the development of complications. But it’s important to say that the amount of data available for today is insufficient to make a unambiguous conclusion

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health