The neurobiological basis and temporal dynamics of communicative language processing pose important yet unresolved questions. It has previously been suggested that comprehension of the communicative function of an utterance, i.e. the so-called speech act, is supported by an ensemble of neural networks, comprising lexico-semantic, action and mirror neuron as well as theory of mind circuits, all activated in concert. It has also been demonstrated that recognition of the speech act type occurs extremely rapidly. These findings however, were obtained in experiments with insufficient spatio-temporal resolution, thus possibly concealing important facets of the neural dynamics of the speech act comprehension process. Here, we used magnetoencephalography to investigate the comprehension of Naming and Request actions performed with utterances controlled for physical features, psycholinguistic properties and the probability of occurrence in variable contexts. The results show that different communicative actions are underpinned by a dynamic neural network, which differentiates between speech act types very early after the speech act onset. Within 50-90 ms, Requests engaged mirror-neuron action-comprehension systems in sensorimotor cortex, possibly for processing action knowledge and intentions. Still, within the first 200 ms of stimulus onset (100-150 ms), Naming activated brain areas involved in referential semantic retrieval. Subsequently (200-300 ms), theory of mind and mentalising circuits were activated in medial prefrontal and temporo-parietal areas, possibly indexing processing of intentions and assumptions of both communication partners. This cascade of stages of processing information about actions and intentions, referential semantics, and theory of mind may underlie dynamic and interactive speech act comprehension.
The prefrontal cortex (PFC) underlies higher cognitive processes1 that are modulated by nicotinic acetylcholine receptor (nAChR) activation by cholinergic inputs2 . PFC spontaneous default activity3 is altered in neuropsychiatric disorders4 , including schizophrenia5 —a disorder that can be accompanied by heavy smoking6 . Recently, genome-wide association studies (GWAS) identified single-nucleotide polymorphisms (SNPs) in the human CHRNA5 gene, encoding the α5 nAChR subunit, that increase the risks for both smoking and schizophrenia7,8. Mice with altered nAChR gene function exhibit PFC-dependent behavioral deficits9–11, but it is unknown how the corresponding human polymorphisms alter the cellular and circuit mechanisms underlying behavior. Here we show that mice expressing a human α5SNP exhibit neurocognitive behavioral deficits in social interaction and sensorimotor gating tasks. Two-photon calcium imaging in awake mouse models showed that nicotine can differentially influence PFC pyramidal cell activity by nAChR modulation of layer II/III hierarchical inhibitory circuits. In α5- SNP-expressing and α5-knockout mice, lower activity of vasoactive intestinal polypeptide (VIP) interneurons resulted in an increased somatostatin (SOM) interneuron inhibitory drive over layer II/III pyramidal neurons. The decreased activity observed in α5-SNP-expressing mice resembles the hypofrontality observed in patients with psychiatric disorders, including schizophrenia and addiction5,12. Chronic nicotine administration reversed this hypofrontality, suggesting that administration of nicotine may represent a therapeutic strategy for the treatment of schizophrenia, and a physiological basis for the tendency of patients with schizophrenia to self-medicate by smoking13.
The author deconstructs the prevailing controversial conceptualization of nonprofit marketing and concludes it rests on three principles: voluntary exchange, an open system organization, and self-interest motivation. Negative case analysis of these principles revealed that alternative principles were ignored in the social science literature. Based on a qualitative analysis a revised conceptualization of non-profit marketing was suggested which incorporated the principles of redistribution and reciprocity, the features of a closed model of formal organization, and public interest motivation. The critical theory approach to the study used non-empirical procedures that included negative case analysis. The paper presents results of negative case analysis.
The major issues hampering progress in the treatment of cancer patients are distant metastases and drug resistance to chemotherapy. Metastasis formation is a very complex process, and looking at gene signatures alone is not enough to get deep insight into it. This paper reviews traditional and novel approaches to identify gene signature biomarkers and intratumoural fluid pressure both as a novel way of creating predictive markers and as an obstacle to cancer therapy. Finally recently developed in vitro systems to predict the response of individual patient derived cancer explants to chemotherapy are discussed.
A series of novel fluorescent pyrimidine nucleosides containing 2,1,3-benzoxadiazole or naphtho[1,2,3-cd]indole-6 (2h)-one fragments was designed and synthesized. Introduction of fluorescent fragments into the position 5 of the uridine or cytidine heterocycle was carried out in two ways: by Sonogashira Coupling Reaction and CuI-catalyzed cycloaddition ("click" reaction). The obtained nucleoside derivatives became fluorescent due to the inserted fragments. The excitation wavelength (440-450 nm) was outside the absorption band of many biomolecules and significantly differed from the emission wavelength (560-600 nm). In addition, the intended nucleoside analogs were shown to kill cultured human tumor cells at submicromolar concentrations
Abstract :Telehealth systems demand standardized solutions to be cost effective and to take advantage of middleware operation and interoperability. The plug-&-play and standard-based platform that, either as individual elements or as components, can be incorporated in a simple way into different homecare environments.Many company, not traditionally involved in medical markets, increasing pressure for a standard for Personal Health Devices (PHD). As a result: ISO/IEEE11073 (X73) standards is adapting from Intensive Unit Care (ICU) scope, focused on the Point-Of-Care (PoC), to Personal Health Devices (PHD), focused on ubiquitous environments, implementing high quality sensors, supporting wireless technologies and providing a faster and more reliable communication network resources. This X73-PHD version is for the homecare challenge and might appear the best-positioned international standards to reach this goal. In this article, a X73 compliant agentand manager communication for homecare platform, as a proof of concept, will be explaining all steps implemented as well as on demand agent specific protocol plugins downloaded to X73 Manager.
In ‘Doing mental health research with children and adolescents. A Guide to qualitative Methods’ (2014), Michell O’Really and Nicola Parker present a highly practical guide to conduct qualitative research with children what extremely easy to follow. The authors show a research process step-by-step with special attention to communicative, ethical and legal issues. The guide is provided by overview of the theories, the importance of research for evidence construction, and most popular qualitative data collection and analysis techniques. In the last chapter, authors discover the successful practice of knowledge dissemination.
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.
1-Substituted 4-perylen-2(3)-y1-1,2,3-triazoles, easily accessible by 'click' reaction and combining in one molecule a polyaromatic unit and a nitrogen heterocycle, were found to strongly inhibit the reproduction of enveloped viruses. 5[4-(Perylen-3-y1)-1,2,3-triazol-1-y1]-uridine and 2-[1-(2-hydroxyethyl)-1,2,3triazol-4-yl]perylene show EC50 of 0.031 and 0.023 mu M, respectively, against tick-borne encephalitis virus (TBEV). Remarkably, the nucleoside unit appears to be not essential for antiviral activity. These results provide deeper understanding of structural basis of activity for this new class of antivirals.
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.