Integrating a dynamic central metabolism model of cancer cells with a hybrid 3D multiscale model for vascular hepatocellular carcinoma growth.

We develop here a novel modelling approach with the aim of closing the conceptual gap between tumour-level metabolic processes and the metabolic processes occurring in individual cancer cells. In particular, the metabolism in hepatocellular carcinoma derived cell lines (HEPG2 cells) has been well characterized but implementations of multiscale models integrating this known metabolism have not been previously reported. We therefore extend a previously published multiscale model of vascular tumour growth, and integrate it with an experimentally verified network of central metabolism in HEPG2 cells.

AFFECTIVE-COGNITIVE INDICATOR OF EMOTIONAL INTELLIGENCE FORMEDNESS IN HIGH SCHOOLERS WITH INTELLECTUAL DISABILITIES.

Objective: The aim is to determine the peculiarities of the affective-cognitive indicator of emotional intelligence in high schoolers with intellectual disabilities.

Patients And Methods: Materials and methods: The study, which was conducted during 2019-2020, involved 76 high schoolers in the age of 14-17 who studied in the 7-9th grades in Kyiv schools (Ukraine) (45 high schoolers with intellectual disabilities and 31 high schoolers with normative development). The diagnosis of the high schoolers' ability to perceive, understand and identify emotions; to assimilate emotions in thoughts, to stimulate thought processes with the help of emotions was carried out.

Synergistically applying 1-D modeling and CFD for designing industrial scale bubble column syngas bioreactors.

The reduction of greenhouse gas emissions and future perspectives of circular economy ask for new solutions to produce commodities and fine chemicals. Large-scale bubble columns operated by gaseous substrates such as CO, CO, and H to feed acetogens for product formations could be promising approaches. Valid in silico predictions of large-scale performance are needed to dimension bioreactors properly taking into account biological constraints, too.

N-Thiazolylamide-based free fatty-acid 2 receptor agonists: Discovery, lead optimization and demonstration of off-target effect in a diabetes model.

Free fatty acid-2 (FFA2) receptor is a G-protein coupled receptor of interest in the development of therapeutics in metabolic and inflammatory disease areas. The discovery and optimization of an N-thiazolylamide carboxylic acid FFA2 agonist scaffold is described. Dual key objectives were to i) evaluate the potential of this scaffold for lead optimization in particular with respect to safety de-risking physicochemical properties, i.

Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II).

Further lead optimization on N-acyl-triazolopiperazine antagonists to the neurokinin-3 receptor (NK3R) based on the concurrent improvement in bioactivity and ligand lipophilic efficiency (LLE) is reported. Overall, compound 3 (LLE > 6) emerged as the most efficacious in castrated rat and monkey to lower plasma LH, and it displayed the best off-target safety profile that led to its clinical candidate nomination for the treatment of sex-hormone disorders.

Discovery and optimization of novel antagonists to the human neurokinin-3 receptor for the treatment of sex-hormone disorders (Part I).

Neurokinin-3 receptor (NK3R) has recently emerged as important in modulating the tonic pulsatile gonadotropin-releasing hormone (GnRH) release. We therefore decided to explore NK3R antagonists as therapeutics for sex-hormone disorders that can potentially benefit from lowering GnRH pulsatility with consequent diminished levels of plasma luteinizing hormone (LH) and correspondingly attenuated levels of circulating androgens and estrogens. The discovery and lead optimization of a novel N-acyl-triazolopiperazine NK3R antagonist chemotype achieved through bioisosteric lead change from the high-throughput screening (HTS) hit is described.

Use of titanium mesh for middle cranial fossa skull base reconstruction.

Objectives Temporal bone encephaloceles are usually encountered in the setting of a congenital defect of the tegmen or as an acquired defect after mastoid surgery. A variety of methods have been described in the literature for rigid reconstruction of tegmen defects. We introduce a new method of repair using orbital floor titanium mesh reconstruction plates to reconstruct the floor of the middle cranial fossa, and evaluate the outcomes, complications, and recurrence rates of temporal bone encephaloceles with this technique.

Morphotype analysis of the sibling vole (Microtus rossiaemeridionalis) casually introduced to the Russian Far East.

Here, we present the morphotypic variety of the m1 and M3 teeth diagnostics for the recently formed isolated population of the sibling vole in Far Eastern Russia. In the Far Eastern population, the prevalence of the individuals with m1 with a complicated crown of the forward unpaired loop of the paraconid is characteristic. Namely, m1 in these individuals shows well-expressed sixth exterior and fifth interior salient angles.

[Accumulation of sodium and potassium ions in oocytes of the river lamprey Lampetra fluviatilis during prespawning period].

Accumulation of Na+ and K+ ions in oocytes of the river lamprey Lampetra fluviatilis and their transport across the plasma membrane is realized by two main mechanisms--Na,K-pump and Na,K,Cl-cotransport. At the prespawning period from December to May the intracellular Na+ concentration was observed to increase from 10 to 25 mM and the K+ concentration--from 28 to 45 mM. Results obtained on isolated oocytes with aid of 204Tl radioactive label have shown that contributions of the Na,K-pump and Na,K,Cl-cotransport to potassium accumulations were close until March.

Agent-based simulation of reactions in the crowded and structured intracellular environment: Influence of mobility and location of the reactants.

Background: In this paper we apply a novel agent-based simulation method in order to model intracellular reactions in detail. The simulations are performed within a virtual cytoskeleton enriched with further crowding elements, which allows the analysis of molecular crowding effects on intracellular diffusion and reaction rates. The cytoskeleton network leads to a reduction in the mobility of molecules.

Multiscale modelling of vascular tumour growth in 3D: the roles of domain size and boundary conditions.

We investigate a three-dimensional multiscale model of vascular tumour growth, which couples blood flow, angiogenesis, vascular remodelling, nutrient/growth factor transport, movement of, and interactions between, normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. In particular, we determine how the domain size, aspect ratio and initial vascular network influence the tumour's growth dynamics and its long-time composition. We establish whether it is possible to extrapolate simulation results obtained for small domains to larger ones, by constructing a large simulation domain from a number of identical subdomains, each subsystem initially comprising two parallel parent vessels, with associated cells and diffusible substances.

[Transport of monovalent thallium across the membrane of oocyte of the lamprey Lampetra fluviatilis].

Mechanisms of transport of monovalent thallium across the membrane of oocyte of the lamprey Lampetra fluviatilis were studied by using 204Tl. Transport of Tl+ in lamprey oocytes has been shown to be realized by at least two pathways: through Na/K-pump and by the mechanism of Na,K,Cl-cotransport. In the standard Ringer solution (mM): 4 KCl, 140 NaCl, 0.

Multi-scale spatio-temporal modeling: lifelines of microorganisms in bioreactors and tracking molecules in cells.

Agent-based models are rigorous tools for simulating the interactions of individual entities, such as organisms or molecules within cells and assessing their effects on the dynamic behavior of the system as a whole. In context with bioprocess and biosystems engineering there are several interesting and important applications. This contribution aims at introducing this strategy with the aid of two examples characterized by striking distinctions in the scale of the individual entities and the mode of their interactions.

[The 75th anniversary of the military hospital in Komsomolsk-on-Amur].

The article is devoted to the 75th anniversary of post hospital in Komsomolsk-on-Amur--chief treatment-prophylaxis institute of Far Eastern Region. Zone of it's responsibility covers 600 km with numerous taiga cities and posts. Hospital is a methodic center, where physicians, pharmaceutists and medical staff of military units improve their qualification.

Stochastic simulation of signal transduction: impact of the cellular architecture on diffusion.

The transduction of signals depends on the translocation of signaling molecules to specific targets. Undirected diffusion processes play a key role in the bridging of spaces between different cellular compartments. The diffusion of the molecules is, in turn, governed by the intracellular architecture.

Combined PCR-DGGE fingerprinting and quantitative-PCR indicates shifts in fecal population sizes and diversity of Bacteroides, bifidobacteria and Clostridium cluster IV in institutionalized elderly.

Aims: This study aimed at determining ageing-related shifts in diversity and composition of key members of the fecal microbiota by comparing institutionalized elderly (n = 17, 78-94 years) and young volunteers (n = 17, 18-31 years).

Methods And Results: A combination of molecular methods was used to characterize the diversity and relative abundance of total gastro-intestinal flora, along with relevant subsets within the genera Bacteroides, bifidobacteria and Clostridium cluster IV. The institutionalized elderly harbored significantly higher numbers of Bacteroides cells than control (28.

[Trans-cultural geriatrics: an incipient challenge].

Besides extended life expectancy, the globalization, increased mobility and migration are additionally influencing the structural change of the society. Thereafter, the problem of multiculturalism, as known within the school system, will soon also become relevant in the geriatrics. Thus, being in a foreign country as an elderly person can aggravate the common geriatric problem of isolation.

[Why should Byzantium be considered as a cradle of clinical geriatrics?].

Generally, roots of today's medical ethics are thought to have sprouted from antiquity and from classical Hebraic consciousness, while the origin of hospital medicine and institutional nursing of the elderly was assumed in Middle Age and in modern times, respectively. But even between these two periods, notably in Byzantium (324-1453) there were many famous physicians working with surprising skills in many disciplines such as surgery and ophthalmology. The most important achievement of that time, however, was in public health care.

Vegetarian diet affects genes of oxidative metabolism and collagen synthesis.

Background/aim: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians.

Methods: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa.

Investigations of reaction kinetics for immobilized enzymes--identification of parameters in the presence of diffusion limitation.

A method is proposed for identification of kinetic parameters when diffusion of substrates is limiting in reactions catalyzed by immobilized enzymes. This method overcomes conventional sequential procedures, which assume immobilization does not affect the conformation of the enzyme and, thus, consider intrinsic and inherent kinetics to be the same. The coupled equations describing intraparticle mass transport are solved simultaneously using numerical methods and are used for direct estimation of kinetic parameters by fitting modeling results to time-course measurements in a stirred tank reactor.

[Limits and relevance of the laboratory diagnosis of malnutrition in the elderly].

Despite the widespread interest in malnutrition in the elderly, the utility of laboratory tests is limited. This is because their diagnostic significance can be impaired by undercurrent diseases, pre-analytical effects and unsatisfactory standardization. This survey summarizes the most important parameters of malnutrition.

Women's use of hormone therapy before and after the Women's Health Initiative: a psychosocial model of stability and change.

Objective: This longitudinal study examined factors underlying hormone therapy (HT) use before and after termination of the landmark Women's Health Initiative (WHI) estrogen plus progestin HT trial in July 2002, after which dramatic reductions in HT use occurred.

Methods: A community sample of 324 women (aged 40-86) from Arizona was interviewed four times between 1995 and 2003. A model of medical and psychological factors underlying intentions for long-term HT use expressed in 1995/1996 was developed and employed to predict subsequent use and discontinued use pre- and post-WHI.