Сell clusters isolation in glioblastomas and their functional and molecular characterization using new morphometric approaches.

BACKGROUND: Digital pathology has come a long way in terms of creating tools to improve existing diagnostic approaches. However, several pathology fields, such as neuropathology, are still characterized by low coverage from machine learning tools and neural network analysis, which may be due to the complexity of the internal cellular and molecular structure of the corresponding neoplasms, including glioblastomas. METHOD: In the framework of this study, using advanced proprietary tools for obtaining images of histological slides and their deep morphometric analysis, we studied samples of 198 patients with glioblastoma with the selection of morphometric cell clusters. Also, cells of each cluster were isolated, and their proliferative, migratory, invasive activity, survival ability, aerobic glycolysis activity, and chemo- and radioresistance were studied. RESULTS: Four morphometric clusters were identified, including small-cell cluster, paracirculonuclear cluster, hypochromic cluster, and macronuclear cluster, which significantly differed in morphometric parameters and functional parameters. Hypochromic cluster cells demonstrated the highest proliferation activity; macronuclear cluster was the most active glucose consumer; paracirculonuclear cluster had the most prominent migratory and invasive activity and hypoxia resistance; small-cell cluster demonstrated predominantly average values of all parameters. Moreover, additional analysis revealed the presence of a separate subcluster of stem cell elements that correspond in their molecular properties to glioma stem cells and are present in all four clusters. It also turned out that several key molecular parameters of glioblastoma, such as mutational modifications in the EGFR, PDGFRA, and NF1 genes, along with the molecular GBM subtype, are significantly correlated with the identified cell clusters. CONCLUSIONS: Thus, the results represent an up-and-coming innovation in the practical field of digital pathology and fundamental questions of glioma carcinogenesis.

[The Concept of Patient-Oriented Model of Organization of Medical Care].

The efficient and rational support of quality om medical care rendering is an important aspect of the system of organization of health care functioning. The study considers the development of concept of patient-oriented model of medical care rendering and also system analysis of main parameters of the model. The study was based on the analysis of publications and normative legislative documents of Minzdrav of Russia and the Federal Foundation of mandatory medical insurance, control boards of health care and territorial Foundations of mandatory medical insurance, subjects of the Russian Federation. The comprehensive analysis resulted in formulation of main parameters and propositions of the patient-oriented model. The concept of related model of organization of medical care rendering to population was presented too. The implementation of the proposed concept in case of its appropriate implementation will favor amelioration of clinical outcomes, increasing of satisfaction and compliance of patients, that will permit to optimize organization of medical care rendering.

Ultrastructurural picture of cyclophosphamide-induced damage to the liver.

We studied the ultrastructural reorganization of hepatocytes and other populations of liver cells after cyclophosphamide treatment. Single administration of cyclophosphamide was followed by significant ultrastructural changes in two major populations of liver cells (hepatocytes and sinusoidal endothelial cells). This treatment was also accompanied by reactive changes in Kupffer cells, lymphocytes, and plasma cells migrating into the spaces of Disse. Cyclophosphamide-induced spatial reorganization of hepatocytes was associated with a progressive decrease in the structural density of mitochondria, significant reduction of the smooth endoplasmic reticulum, and increase in autophagocytosis (e.g., sequestration of glycogen). Intracellular reorganization of endothelial cells was related to the following two factors: damage (necrobiosis) of some cells; and increase in metabolic processes, phagocytosis, and regenerative reactions in other cells.