The search for novel parameters to predict the risk of relapse in breast cancer was conducted. Significant correlation between the risk of relapse and α-2A adrenergic receptor (ADRA2A) expression was revealed using public microarray datasets. This relationship was confirmed by validation on independent microarray dataset. It was found that when assessing the risk of BC relapse, the accuracy of prediction based solely on the expression of ADRA2A gene is close to that made using OncotypeDX and MammaPrint test systems. In this case, addition of only one or two supplemental prognostic markers (for instance, expression of SQLE gene or SQLE andDSCC1genes) to ADRA2A ensures the accuracy of prediction not inferior to reliability of these test systems.
The paper presents a formalized statement of the problem of selecting parameters and construction of a genomic classifier for medical test systemswith mathematical methods of machine learning without the use of biological and medical knowledge. A method is proposed to solve this problem. The results of testing the method using microarray datasets containing information on genome-wide transcriptome of the samples of estrogen positive breast tumors are discussed. Testing showed that the quality of classification provided by the constructed test system and implemented on the basis of assessments of expression of 12 genes is not inferior to the quality of classification carried out by such test systems as OncotypeDX and MammaPrint.
Sensory and cognitive deficits are common in schizophrenia. They are associated with abnormal brain rhythms, including disturbances in γ frequency (30–80 Hz) oscillations (GFO) in cortex-related networks. However, the underlying anatomofunctional mechanisms remain elusive. Clinical and experimental evidence suggests that these deficits result from a hyporegulation of glutamate N-methyl-D-aspartate receptors. Here we modeled these deficits in rats with ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist and a translational psychotomimetic substance at subanesthetic doses. We tested the hypothesis that ketamine-induced sensory deficits involve an impairment of the ability of the thalamocortical (TC) system to discriminate the relevant information from the baseline activity. Furthermore, we wanted to assess whether ketamine disrupts synaptic plasticity in TC systems. We conducted multisite network recordings in the rat somatosensory TC system, natural stimulation of the vibrissae and high-frequency electrical stimulation (HFS) of the thalamus. A single systemic injection of ketamine increased the amount of baseline GFO, reduced the amplitude of the sensory-evoked TC response and decreased the power of the sensory-evoked GFO. Furthermore, cortical application of ketamine elicited local and distant increases in baseline GFO. The ketamine effects were transient. Unexpectedly, HFS of the TC pathway had opposite actions. In conclusion, ketamine and thalamic HFS have opposite effects on the ability of the somatosensory TC system to discriminate the sensory-evoked response from the baseline GFO during information processing. Investigating the link between the state and function of the TC system may conceptually be a key strategy to design innovative therapies against neuropsychiatric disorders.
The significance of biotechnologies for solving global problems and making social and economic progress is recognized in many countries, including Russia. Managing this field requires up-to-date and reliable information about technological trends and the emergence and diffusion of innovations. This paper examines the possibility of applying a patent-based methodological approach to the study of biotechnologies in Russia, and assesses its explanatory potential.
This review presents current data on possible mechanisms forming synergies in health, particularly at the cortical level. The mechanisms of formation of pathological synergies, taking account of the anatomical and physiological characteristics of the upper limbs and the hypothesis, that synergistic patterns are transformed in patients with spastic hemiparesis are discussed. Current views of the pathophysiological bases of the formation of pathological synergies based on neuroimaging and neurophysiological study data are presented, along with a method for noninvasive stimulation of the brain. The question of the correction and transformation of pathological synergies in rehabilitation practice is discussed. Particular attention is paid to clinical and instrumented evaluation of synergies and the use of validated clinical scales and instrumented methods such as video movement analysis, electromyography, magnetic and contactless tracking systems, and virtual reality technologies.
Many countries have recently started the search for new payments methods with the specific objective to encourage the integration in service delivery. This paper suggests their typology. A brief overview of these methods in the USA and Europe, including Russia, indicates that there is still no strong evidence of their effects on integration and other dimensions of service delivery performance. It is argued that relative to other integrated methods global payment is the most promising method, since it provides incentives for comprehensive organizational changes. But this method is hard to implement – mostly due to a high probability of excessive financial risks placed on providers in integrated networks. The activities to mitigate these risks are discussed based on the approaches used in the Alternative Quality Contract in Massachusetts and fundholding scheme in Russia. The major pre-conditions for global payment implementation are specified: involvement of hospitals in global payment schemes, shared savings arrangements, special set of activities to mitigate financial risks, performance transparency system. It is also argued that there is a dilemma of strong economic incentives with serious implementation problems and lower economic incentives with less substantial implementation problems.
Allostatic load theory implies a relationship between exposure to psychological stress and multi-system physiological dysregulation. We used data from population-based samples of men and women in Russia (Moscow; n = 1800; age, mean 68.6 years), Taiwan (n = 1036; 65.6 years) and the United States (US; n = 1054; 58.0 years) -- which are likely to vary widely with respect to levels of stress exposure and biological markers -- to determine the magnitude of the association between perceived stress and physiological dysregulation. The measure of overall dysregulation was based on 15 markers including standard cardiovascular/metabolic risk factors as well as markers of inflammation and neuroendocrine activity. Subjective psychological stress was measured by the perceived stress scale. Only the Moscow sample demonstrated a positive association with overall dysregulation in both sexes. In the US, we found an association among women but not men. Among the Taiwanese, who report the lowest perceived stress, there was no association in women but an unexpected inverse relationship in men. The effects also varied across system-level subscores: the association with perceived stress was most consistent for standard cardiovascular/metabolic factors. Perceived stress was associated with inflammation and neuroendocrine activity in some samples. Although the evidence that perceived stress is the primary source of physiological dysregulation is generally modest, it was stronger in Russia where the level of perceived stress was particularly high. For Russia only, we had information about heart function based on a 24 h ambulatory electrocardiogram; perceived stress was consistently associated with heart rate dysregulation in Russian men and women.
An analysis of international data on opinions on how health care systems should be organized and on the ways in which care should be delivered shows that inequality in accessis seen as a problem in all countries, but that Russians rank highest on this value.
Increasing evidence suggests that neuronal communication is a defining property of functionally specialized brain networks and that it is implemented through synchronization between population activities of distinct brain areas. The detection of long-range coupling in electroencephalography (EEG) and magnetoencephalography (MEG) data using conventional metrics (such as coherence or phase-locking value) is by definition contaminated by spatial leakage. Methods such as imaginary coherence, phase-lag index or orthogonalized amplitude correlations tackle spatial leakage by ignoring zero-phase interactions. Although useful, these metrics will by construction lead to false negatives in cases where true zero-phase coupling exists in the data and will underestimate interactions with phase lags in the vicinity of zero. Yet, empirically observed neuronal synchrony in invasive recordings indicates that it is not uncommon to find zero or close-to-zero phase lag between the activity profiles of coupled neuronal assemblies. Here, we introduce a novel method that allows us to mitigate the undesired spatial leakage effects and detect zero and near zero phase interactions. To this end, we propose a projection operation that operates on sensor-space cross-spectrum and suppresses the spatial leakage contribution but retains the true zero-phase interaction component. We then solve the network estimation task as a source estimation problem defined in the product space of interacting source topographies. We show how this framework provides reliable interaction detection for all phase-lag values and we thus refer to the method as Phase Shift Invariant Imaging of Coherent Sources (PSIICOS). Realistic simulations demonstrate that PSIICOS has better detector characteristics than existing interaction metrics. Finally, we illustrate the performance of PSIICOS by applying it to real MEG dataset recorded during a standard mental rotation task. Taken together, using analytical derivations, data simulations and real brain data, this study presents a novel source-space MEG/EEG connectivity method that overcomes previous limitations and for the first time allows for the estimation of true zero-phase coupling via non-invasive electrophysiological recordings.
Background: The oxytocin (OT) system is known to be implicated in the regulation of complex social behavior, particularly empathy and parenting. The goal of this study was to estimate the gender and population differences in polymorphisms of two oxytocin receptor gene SNPs, rs53576 and rs2254298, in four populations. Results: These data were compared with each other and with 14 samples from the corresponding regions retrieved from the 1000 Genomes database. Low level of heterozygosity was observed for both SNPs in all populations in this study (rs53576: Catalonian, Hobs = 0.413; Hadza, Hobs = 0.556; sr2254698: Khanty-Mansi, Hobs = 0.250; Datoga, Hobs = 0.550). The amount of variance due to regional variability was almost equal for both SNPs (rs53576: FRT = 0.086, rs2554298: FRT = 0.072), whereas variance for the population level of variability was twice bigger for rs2554298 (rs53576: FST = 0.127, rs2554298: FST = 0.162). Pairwise coefficients of fixation demonstrate that the Hadza were well differentiated from other African populations except of Datoga, the Datoga were weakly differentiated from other African origin populations, the Ob Ugric people were extremely differentiated from all other populations. Catalans were extremely differentiated of Asian populations. Conclusions: It is hypothesized on the base of spatial distribution of the evolutionary novel A alleles of the both OXTR gene loci, that the spread of alleles of rs22542298 and rs53376 SNPs may be associated to some extant with manipulation of parental investment in humans.
This article of the International Epidemiological Association commissioned paper series stocktakes the population health and status of epidemiology in 21 of the 53 countries of the WHO European Region. Published data were used to describe population health indicators and risk factors. Epidemiological training and research was assessed based on author knowledge, information searches and E-mail survey of experts. Bibliometric analyses determined epidemiological publication outputs.
Between-country differences in life expectancy, amount and profile of disease burden and prevalence of risk factors are marked. Epidemiological training is affected by ongoing structural reforms of educational systems. Training is advanced in Israel and several Eastern European countries. Epidemiological research is mainly university-based in most countries, but predominantly conducted by governmental research institutes in several countries of the former Soviet Union. Funding is generally external and limited, partially due to competition from and prioritization of biomedical research. Multiple relevant professional societies exist, especially in
Poland, the Czech Republic and Hungary. Few of the region’s 39 epidemiological academic journals have international currency. The number of epidemiological publications per population is highest for Israel and lowest for South-Central Asian countries.
Epidemiological capacity will continue to be heterogeneous across the region and depend more on countries’ individual historical, social, political and economic conditions and contexts than their epidemiologists’ successive efforts
In June 2016 the European Commission presented criteria to identify endocrine disruptors in the field of plant protection products and biocides(1). The documents approved are instruments for the move to the practice from the WHO general approach with its definition “Endocrine disruptors are substances, both natural and chemical, that can alter the functions of the hormonal system and consequently cause adverse effects on people or animals.”(2) The further excerpt provides the understanding of the state of the science under the regulatory efforts: “although it is clear that certain environmental chemicals can interfere with normal hormonal processes, there is weak evidence that human health has been adversely affected by exposure to endocrine-active chemicals. However, there is sufficient evidence to conclude that adverse endocrine‐mediated effects have occurred in some wildlife species”. This was concluded in 2002, and in 2012 (latest report(2)) evidence base did not improved significantly. Especially it is weak for the effects in humans. It would not be a hyperbolae to say that there is no direct evidence that “endocrine disruptors” as natural or synthetic substances in the environment harms people.
An analysis of prevalence and associated common risk factors of ED and lower urinary tract symptoms (LUTS) was performed in Russian Federation by cross-sectional multicenter survey. International Index of Erectile Function (IIEF) score and International Prostate Symptom Score (IPSS) were used for data collection in 1225 men between 20 and 77 years interviewed in six regions of Russian Federation. In addition, each participant's social, demographic, lifestyle, sexual and medical history was taken with special emphasis on risk factors for ED. Upon the basis of IIEF erectile domain score interpretation, ED was found in 530 (48.9%) men, consisting of mild and mild to moderate, moderate and severe ED in 375 (34.6%), 78 (7.2%) and 77 (7.1%) respondents, respectively. According to IPSS assessment, LUTSs were present in 649 (59.9%) responders; inclusive 370 (34.2%), 216 (19.9%) and 63 (5.8%) men with mild, moderate and severe LUTS, respectively. Men with both ED and LUTS shared common co-morbidities and lifestyle risk factors with age-adjusted odds ratio between 1.2 and 5.2. In logistic regression model (R2=0.361), the strongest associated with ED factor found was IPSS symptom score, followed by hypertension, IPSS-related quality of life, age, diabetes mellitus, obesity and unmotivated fatigue
In studies of massive changes in social life, researchers often have to rely on low-quality retrospective data such as memoirs and manipulated government reports as opposed to reliable data such as vital registration. The dissolution of the Soviet Union in 1991 was an unpredictable event with large-scale consequences for the lives of millions of Russians. Beginning in the 1960s, the Soviet Union started to fall into a deep demographic crisis.1 The end of Communism was accompanied by a further increase in total mortality, with unprecedented fluctuations during the next two decades. Several studies were done in a bid to explain this.2
This paper briefly analyzes the quality of cause-specific mortality statistics at old ages in Russia. Two aspects were the focus of the work: the regional differences in approaches for choosing the underlying cause of death and the comparison of the Russian coding practice with the practices of several other European countries. The results of the study indicate that there are certain problems with the quality of cause-of-death coding at old ages in Russia. No unified approach to coding deaths caused by senility is used at the subnational level, which leads to the distortion of the regional cause-specific mortality structures. Furthermore, for many groups of causes Russian death rates are much lower than those in European countries. This peculiarity is caused by the specificity of the Russian cause-of-death coding practice, which results in underestimating the mortality from certain causes at old ages.
BACKGROUND AND PURPOSE Acid-sensing ion channels (ASICs) play an important role in synaptic plasticity and learning, as well as in nociception and mechanosensation. ASICs are involved in pain and in neurological and psychiatric diseases, but their therapeutic potential is limited by the lack of ligands activating them at physiological pH. EXPERIMENTAL APPROACH We extracted, purified and determined the structure of a bisbenzylisoquinoline alkaloid, lindoldhamine, (LIN) from laurel leaves. Its effect on ASIC3 channels were characterized, using two-electrode voltage-clamp electrophysiological recordings from Xenopus laevis oocytes. KEY RESULTS At pH 7.4 or higher, LIN activated a sustained, proton-independent, current through rat and human ASIC3 channels, but not rat ASIC1a or ASIC2a channels. LIN also potentiated proton-induced transient currents and promoted recovery from desensitization in human, but not rat, ASIC3 channels. CONCLUSIONS AND IMPLICATIONS We describe a novel ASIC subtype-specific agonist LIN, which induced proton-independent activation of human and rat ASIC3 channels at physiological pH. LIN also acts as a positive allosteric modulator of human, but not rat, ASIC3 channels. This unique, species-selective, ligand of ASIC3, opens new avenues in studies of ASIC structure and function, as well as providing new approaches to drug design.
To explore the influence of psychiatric distress and substance use on viral load suppression in HIV-infected patients taking ART we analyzed socio-demographic characteristics, CD4+ cells count and viral loads, the Symptom Check List-90 and the Addiction Severity Index of 75 patients who had taken ART for at least 6 month. Using viral load data as the marker of ART success, we divided the sample into two groups. Comparison of the groups showed that education, marriage, and female gender are predictors of optimal viral load suppression. Overall results failed to demonstrate substance use and psychiatric distress as predictors of viral load suppression
Adenosine serves many functions within the CNS, including inhibitory and excitatory control of neurotransmission. The understanding of adenosine dynamics in the brain is of fundamental importance. The goal of the present study was to explore subsecond adenosine fluctuations in the rat brain in vivo.
Long Evans rats were anesthetized and a carbon fiber electrode was positioned in the motor cortex or dorsal striatum. Real time electrochemical recordings were made at the carbon fiber electrodes every 100ms by applying a triangular waveform (-0.4 to +1.5V, 400V/s). Adenosine spikes were identified by the background-subtracted cyclic voltammogram.
The frequency of detected adenosine spikes was relatively stable in both tested regions, and the time intervals between spikes were regular and lasted from 1 to 5s within an animal. Spike frequency ranged from 0.5 to 1.5Hz in both the motor cortex and the dorsal striatum. Average spike amplitudes were 85±11 and 66±7nM for the motor cortex and the dorsal striatum, respectively.
COMPARISON WITH EXISTING METHODS:
The current study established that adenosine signaling can operate on a fast time scale (within seconds) to modulate brain functions.
This finding suggests that spontaneous adenosine release may play a fast, dynamic role in regulating an organism's response to external events. Therefore, adenosine transmission in the brain may have characteristics similar to those of classical neurotransmitters, such as dopamine and norepinephrine.