Genetic and epigenetic changes in primary metastatic and nonmetastatic colorectal cancer

Colorectal cancer (CRC) develops as multistep process, which involves genetic and epigenetic alterations. K-Ras, p53 and B-Raf mutations and RASSF1A, E-Cadherin and p16INK4A promoter methylation were investigated in 202 CRCs with and without lymph node and/or liver metastasis, to assess whether gene abnormalities are related to a metastogenic phenotype. K-Ras, B-Raf and p53 mutations were detected in 27, 3 and 32% of the cases, with K-Ras mutations significantly associated with metastatic tumour (P=0.019). RASSF1A, E-Cadherin and p16INK4A methylation was documented in 20, 44 and 33% of the cases with p16INK4A significantly associated with metastatic tumours (P=0.001). Overall, out of 202 tumours, 34 (17%) did not show any molecular change, 125 (62%) had one or two and 43 (21%) three or more. Primary but yet metastatic CRCs were prevalent in the latter group (P=0.023) where the most frequent combination was one genetic (K-Ras in particular) and two epigenetic alterations. In conclusion, this analysis provided to detect some molecular differences between primary metastatic and nonmetastatic CRCs, with K-Ras and p16INK4A statistically altered in metastatic tumours; particular gene combinations, such as coincidental K-Ras mutation with two methylated genes are associated to a metastogenic phenotype

Study of social network interference of memory processes in adolescence

Memory is the fundamental basis of human learning. Conceptual assessment and study of the memory mechanisms, its formation, consolidation and preservation at different levels of the structural and functional organization of the nervous system constitutes the necessary knowledge for solving many problems of practical and fundamental psychology. This article presents the study of memory, namely the process of its transition from a short-term to a more stable long-term form in a digital environment under the influence of the interference factor of social networks. The aim of the work is to study the influence of the social network interference factor on the processes of consolidation and reconsolidation of memory in adolescence. The total sample size was 68 adolescents aged 12–17 years. The authors conducted an experiment to achieve this goal. Its results showed that adolescents have difficulty remembering information in the form of short, successive videos in the digital space. It was found that videos that are characterized not only by visual accompaniment, but also by speech production are subject to better memorization. Under the influence of the interfering factor of social networks, adolescents faced difficulties in linking individual elements of stimuli with each other – they connected elements of one video with elements of another. According to one of the provisions of the theory of interference, information storage is characterized by the “unbinding” of representations of objects, followed by their reverse linking in an arbitrary combination during further reproduction

Polarization Switching Between Electric and Magnetic Quasi-Trapped Modes in Bianisotropic All-Dielectric Metasurfaces

A general strategy for the realization of electric and magnetic quasi-trapped modes located at the same spectral position is presented. This strategy's application makes it possible to design metasurfaces allowing switching between the electric and magnetic quasi-trapped modes by changing the polarization of the incident light wave. The developed strategy is based on two stages: the application of the dipole approximation for determining the conditions required for the implementation of trapped modes at certain spectral positions and the creation of the energy channels for their excitation by introducing a weak bianisotropy in nanoparticles. Since excitation of trapped modes results in a concentration of electric and magnetic energies in the metasurface plane, the polarization switching provides possibilities to change and control the localization and distribution of optical energy at the sub-wavelength scale. A practical method for spectral tuning of quasi-trapped modes in metasurfaces composed of nanoparticles with a preselected shape is demonstrated. As an example, the optical properties of a metasurface composed of silicon triangular prisms are analyzed and discussed

Bioregulation of amplitude-phase biological activity of Candida albicans by women reproductive tract microsymbionts

In this study, we propose a chronobiological method for examining inter-microbial interactions in bacterial and fungal associations in female reproductive tract. Fungal and bacterial species were isolated in 45 women of reproductive aged 19–35, with regular menstrual cycle, applying no hormonal contraceptives, without previous gynecological surgery, abortions, miscarriages with vaginal eubiosis and dysbiosis in history. Sexually transmitted diseases (HIV infection, syphilis, gonorrhea, trichomoniasis, chlamydiosis) were excluded in all subjects. Proliferation rate, morphogenesis and phospholipase activity were examined within the 48-hour period every 4 hours, in winter time, Moon phase IV. The data obtained were assessed by using Student’s t-test, Wilcoxon test, and least squares method. All subjects were divided into the groups: group 1 — women with vaginal eubiosis, group 2 — women with vaginal dysbiosis. It was shown that in all subjects experimental parameters of C. albicans cultures showed a diurnal dynamics characterized in healthy women by circadian rhythms with a single peak of activity. However, in women with vaginal dysbiosis C. albicans was characterized by significant ultradian (around 12 hours long) rhythms with two peaks of biological activity. Concurrence and consistency in manifested physiological functions related to clinical isolates was coupled to temporal pattern of distributed biological resources in fungi depending on course of infectious process. It was found that in vaginal eubiosis exometabolites released by dominant associated microbiota did not significantly change microbiota-related amplitude-phase parameters. The data obtained evidenced that temporal pattern of parameters related to C. albicans from healthy individuals was stable and independent on bacterial metabolites. In contrast, dominant microsymbiont in vaginal dysbiosis inhibited fungi-related rhythms, which might be important in establishing lactobacillus-associated biotope colonization resistance. Effects of metabolites released by the associated microbiota typical to dysbiosis was revealed by increased mesor, amplitude, preserved biorhythm spectral pattern in examined properties as well as amplitude-phase characteristics indicating at enhanced or sustained C. albicans adaptive potential. Therefore, the amplitude-phase parameter of C. albicans physiological activity served as a marker of opposite (enhanced/weakened) effect of microsymbiont survival described in “microbial dominant-associate” pairs

The combined effects of the microcirculatory status and cardiopulmonary bypass on platelet count and function during cardiac surgery

ACKGROUND: Cardiac surgery with cardiopulmonary bypass is associated with important changes in the microcirculation, usually attributed to endothelial dysfunction. Another common finding of cardiac surgery is postoperative thrombocytopenia and platelet loss of function. OBJECTIVE: To investigate the association between microvascular flow pattern and postoperative changes in platelet count and function in cardiac surgery patients. METHODS: Twelve adult cardiac surgery patients received microvascular circulation (sidestream darkfield sublingual mucosa analysis) and platelet count and function (multiple electrode aggregometry ADPtest and TRAPtest) assessment before and after cardiopulmonary bypass. RESULTS: After cardiopulmonary bypass, sublingual microcirculation showed a significantly (P = 0.001) decreased microvascular flow index and increased heterogeneity index (P = 0.006). Platelet function significantly decrease after cardiopulmonary bypass both at ADPtest (P = 0.011) and TRAPtest (P = 0.002). Preoperative patterns of poor microvascular perfusion (low perfused vessels density and total vessels density) were significantly associated with lower values of post-cardiopulmonary bypass platelet function (ADPtest, P = 0.009, TRAPtest, P = 0.031) and count (P = 0.048). CONCLUSIONS: A preoperative disturbance of the microcirculation is associated with a greater postoperative platelet dysfunction. Endothelial damage, chemical and mechanical stimuli are the possible link between the two patterns

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies

Эффективная модель диспансеризации и динамического наблюдения за пациентами с глаукомой

Open-angle glaucoma is a chronic progressive optic neuropathy characterized by morphological changes in the optic nerve head and retinal nerve fibers layer in the absence of other eye diseases.Regular medical check-ups are necessary to assess the progression of glaucoma, to correct the treatment regimen or prescribe surgical interventions, to control the stabilization of the glaucoma process and to preserve visual functions for longer period. When planning the number of monitoring visits, it is necessary to carefully study the prognostic risk factors, since they are statistically associated with the development and progression of glaucoma. Closer observation of patients with glaucoma reduces the risk of irreversible changes in the organ of vision.Patient compliance is of particular importance in the progression of glaucoma. The adherence rate in the treatment of glaucoma is relatively lower compared to other chronic diseases that require lifelong treatment.Currently, there is no effective model of regular checkups for glaucoma patients, therefore this direction requires improvement and development, both in the standards and timing of patient examination, and in the use of remote methods of glaucoma control. The disadvantage of the current medical check-ups routine is the lack of individual approach to patients, lack of equipment in the offices of regional ophthalmologists, and lack of specialized glaucoma offices.The tense epidemiological situation during the Covid-19 pandemic, gave understanding that while in-person consultations and remote consultations (telemedicine) cannot replace each other, a combination of these methods is cost-effective, can reduce the uneven distribution of ophthalmic resources, reduce the burden on the doctor and the rate of misdiagnosis. The situation was aggravated by the closure of ophthalmological hospitals and an increase in the waiting time for consultation in higher specialized medical institutions, which probably entails an increase in patients with progression of the glaucomatous process and the economic burden on both the state and the patients themselves.Telemedicine should be gradually introduced into everyday practice, for which it is advisable to create a single database of glaucoma patients to track the glaucomatous process.Открытоугольная глаукома — хроническая прогрессирующая оптиконейропатия, характеризующаяся морфологическими изменениями диска зрительного нерва и слоя нервных волокон сетчатки при отсутствии других глазных заболеваний.Диспансерное наблюдение необходимо для оценки прогрессирования глаукомы, коррекции лечения или назначения хирургических вмешательств, для контроля стабилизации глаукомного процесса и более долгого сохранения зрительных функций. При планировании количества диспансерных осмотров необходимо тщательное изучение прогностических факторов риска, так как статистически они связаны с развитием и прогрессированием глаукомы. Более внимательное наблюдение за пациентами с глаукомой снижает риск необратимых изменений органа зрения.Особо важное место в прогрессировании глаукомы занимает комплаентность пациентов. Показатель приверженности при лечении глаукомы относительно ниже по сравнению с другими хроническими заболеваниями, которые также требуют пожизненного лечения.В настоящее время отсутствует эффективная модель диспансерного наблюдения глаукомных пациентов, поэтому данное направление требует усовершенствования и развития как в стандартах и сроках обследования пациентов, так и в использовании дистанционных методов контроля глаукомы. Недостатком нынешней диспансеризации является отсутствие индивидуального подхода к заболевшему, недостаточность оснащения районных кабинетов офтальмологов и недостаток глаукомных кабинетов.Благодаря напряженной эпидемиологической обстановке во время эпидемии COVID-19 было выявлено, что методы очной консультации и телемедицины не могут заменить друг друга, но комбинация этих методов экономически эффективна, может уменьшить неравномерное распределение офтальмологических ресурсов, снизить нагрузку на врача и уровень ошибочного диагноза. Усугубило ситуацию закрытие офтальмологических стационаров и увеличение времени ожидания консультации в вышестоящих специализированных медучреждениях, что наверняка влечет за собой увеличение числа пациентов с прогрессированием глаукомного процесса и экономической нагрузки как на государство, так и на самих пациентов.Следует постепенно внедрять в каждодневную практику телемедицину, для чего целесообразно создание единой базы глаукомных пациентов для отслеживания глаукомного процесса

Milestones in the Observations of Cosmic Magnetic Fields

Magnetic fields are observed everywhere in the universe. In this review, we concentrate on the observational aspects of the magnetic fields of Galactic and extragalactic objects. Readers can follow the milestones in the observations of cosmic magnetic fields obtained from the most important tracers of magnetic fields, namely, the star-light polarization, the Zeeman effect, the rotation measures (RMs, hereafter) of extragalactic radio sources, the pulsar RMs, radio polarization observations, as well as the newly implemented sub-mm and mm polarization capabilities. (Another long paragraph is omitted due to the limited space here)Comment: Invited Review (ChJA&A); 32 pages. Sorry if your significant contributions in this area were not mentioned. Published pdf & ps files (with high quality figures) now availble at http://www.chjaa.org/2002_2_4.ht