Infant mortality in Russia has been decreasing for several decades. In 2011, however, Russia’s infant mortality rate reached a level (7.4 per 1000 live births) more than three times higher than in countries with minimal levels. In April 2012, Russia adopted new definitions of live births and stillbirths, which are much closer to the corresponding WHO definitions than those used before. The transition to these new definitions was meant to increase the rates of perinatal, early neonatal and infant mortality in general for children weighing up to 1000 grams – those concerned by the changed definition. This paper analyzes the changes in the structure and dynamics of death in children under one year of age since the transition to the new definitions of live births and stillbirths, according to birth weight and period of death based on official and medical statistics. It looks at the possibility of distortion of both infant and perinatal mortality and their components. Particular attention is given to an analysis of the structure of infant mortality by age and cause of death in Russia in comparison with other countries. The regional aspect of changes in infant mortality for 2011-2012 is also studied herein.
Prolonged high temperatures and air pollution from wildfires often occur together, and the two may interact in their effects on mortality. However, there are few data on such possible interactions.
Methods: We analyzed day-to-day variations in the number of deaths in Moscow, Russia, in relation to air pollution levels and temperature during the disastrous heat wave and wildfire of 2010. Corresponding data for the period 2006-2009 were used for comparison. Daily average levels of PM10 and ozone were obtained from several continuous measurement stations. The daily number of nonaccidental deaths from specific causes was extracted from official records. Analyses of interactions considered the main effect of temperature as well as the added effect of prolonged high temperatures and the interaction with PM10
Hand motor recovery prognosis in stroke patients is crucial to develop a realistic individual rehabilitation plan. The aim of this study was to perform a multimodal assessment in chronic ischemic stroke patients and to compare predictive role of corticospinal tract (CST) integrity measured by diffusion tensor imaging (DTI) and navigated TMS (nTMS), and functional condition of the motor cortex measured by functional MRI (fMRI) and multi-muscle nTMS cortical mapping for hand motor recovery.Total of 30 patients with the only chronic supratentorial ischemic stroke and various severity of hand paresis were enrolled (12 females, medium age 50,0±8,0). The assessment included fractional anisotropy FA (index, %) measurement in internal capsule (ic), cerebral peduncle (pc) and pons. Functional assessment included analysis of BOLD response induced by passive motor task, assessment of intracortical inhibition (SICI) and intracortical facilitation (ICF) phenomena in Abductor Pollicis Brevis (APB) and nTMS mapping of APB and Extensor Digitorum Communis (EDC) cortical representations in both hemispheres. A group of 14 healthy volunteers (7 females, mean age 36,6±15,2) completed fMRI and nTMS investigation. A strong correlation between clinical outcome and FA let to consider FA as an available clinical measurement for hand motor prognosis. Significantly higher disinhibition in the unaffected hemisphere (UH) in well recovered and normal SICI in the UH in poorly recovered patients allow to suppose that interhemispheric interaction might change extensively by chronic phase. A software for multi-muscle nTMS mapping was developed, though this approach need deeper exploration.
In vivo evaluation of the brain white matter maturation is still a challenging task with no existing gold standards. In this article we propose an original approach to evaluate the early maturation of the white matter bundles, which is based on comparison of infant and adult groups using the Mahalanobis distance computed from four complementary MRI parameters: quantitative qT1 and qT2 relaxation times, longitudinal λ║ and transverse λ⊥ diffusivities from diffusion tensor imaging. Such multi-parametric approach is expected to better describe maturational asynchrony than conventional univariate approaches because it takes into account complementary dependencies of the parameters on different maturational processes, notably the decrease in water content and the myelination. Our approach was tested on 17 healthy infants (aged 3- to 21-week old) for 18 different bundles. It finely confirmed maturational asynchrony across the bundles: the spino-thalamic tract, the optic radiations, the cortico-spinal tract and the fornix have the most advanced maturation, while the superior longitudinal and arcuate fasciculi, the anterior limb of the internal capsule and the external capsule have the most delayed maturation. Furthermore, this approach was more reliable than univariate approaches as it revealed more maturational relationships between the bundles and did not violate a priori assumptions on the temporal order of the bundle maturation. Mahalanobis distances decreased exponentially with age in all bundles, with the only difference between them explained by different onsets of maturation. Estimation of these relative delays confirmed that the most dramatic changes occur during the first post-natal year.
Key characteristics of non-fluent (Broca, motor) aphasia are, among others, verb finding difficulties and effortful speech output. These characteristics are related to different levels of speech production (lexical retrieval and motor execution). This study was aimed at identifying patterns of its reorganization depending on the locus of the linguistic deficit in patients with non-fluent aphasia.
The efficacy of anthracycline based anticancer drugs is limited by pleiotropic drug resistance of tumor cells. Aiming at the design of anthracyclinone congeners capable of circumventing drug resistance, we synthesized naphthoindole containing derivatives of tryptophan and tryptamine. In doing so we adapted the traditional, gramine based approach for tryptophan and tryptamine synthesis. The most potent new compound, 3-(2-aminoethyl)-4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione (16), was equally cytotoxic (IC50 within low micromolar concentrations) for human K562 leukemia and HCT116 colon carcinoma cell lines and their isogenic sublines with genetically defined determinants of altered drug response, that is, the expression of the multidrug transporter P-glycoprotein and loss of pro-apoptotic p53. Each of these mechanisms conferred resistance to the reference drug adriamycin. In contrast, naphthotryptamine 16, although less potent than adriamycin, was equally toxic for wild type cell lines and drug resistant counterparts. Moreover, at 3-5 μM 16 inhibited topoisomerase I in vitro. Thus, our novel naphthoindole based derivative of tryptamine gained new activities important for anticancer therapy, namely, suppression of topoisomerase I and the ability to overcome resistance mediated by P-glycoprotein expression and p53 dysfunction.
With rapid growth of online social network sites, the issue of health-related online communities and its social and behavioral implications has become increasingly important for public health. Unfortunately, online communities often become vehicles for promotion of pernicious misinformation, in particular, that HIV virus is a myth (AIDS denialism). This study seeks to explore online users’ behavior and interactions within AIDS-denialist community to identify and estimate the number of those, who potentially are most susceptible to AIDS-denialist arguments—“the risk group” in terms of becoming AIDS denialists. Social network analysis was used for examining the most numerous AIDS-denialist community (over 15,000 members) in the most popular Russian SNS “VK.com.” In addition, content analysis was used for collecting data on attitudes toward AIDS-denialist arguments and participants’ self-disclosed HIV status. Two data sets were collected to analyze friendship ties and communication interactions among community members. We have identified the core of online community—cohesive and dedicated AIDS denialists, and the risk group: users who communicate with core members, and, thus, can be more susceptible to the AIDS-denialist propaganda and their health behaviors (e.g., refusing treatment). Analysis allowed to significantly reduce the target audience for possible intervention campaigns and simultaneously increase the accuracy of determining the risk group composition.
Humans are unique in developing large lexicons as their communication tool; to achieve this, they are able to learn new words rapidly. However, neural bases of this rapid learning, which may be an expression of a more general cognitive mechanism likely rooted in plasticity at cellular and synaptic levels, are not yet understood. In this update, the author highlights a selection of recent studies that attempted to trace word learning in the human brain noninvasively. A number of brain areas, most notably in hippocampus and neocortex, appear to take part in word acquisition. Critically, the currently available data not only demonstrate the hippocampal role in rapid encoding followed by slow-rate consolidation of cortical word memory traces but also suggest immediate neocortical involvement in the word memory trace formation. Echoing early behavioral studies in ultra-rapid word learning, the reviewed neuroimaging experiments can be taken to suggest that our brain may effectively form new cortical circuits online, as it gets exposed to novel linguistic patterns in the sensory input.
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.
Paired-pulse transcranial magnetic stimulation (TMS) allows investigating inhibitory and excitatory interactions in the human motor cortex noninvasively. Short-interval intracortical inhibition (SICI) and facilitation (SICF) are used to measure cortico–cortical excitability in patients with, e.g., stroke, dystonia, and Parkinson’s disease. However, the role of the induced electric field (E-field) orientation remains partly unclear. Posterior–anterior (PA)-oriented E-field elicits motor evoked potentials (MEPs) with the lowest stimulus intensities due to the recruitment of corticospinal neurons, indirectly via excitatory synaptic inputs to corticospinal axons (indirect (I-) waves). Stimulation in the lateral–medial (LM) orientation directly activates corticospinal axons, which leads to the generation of both direct (D-) and I-waves. Conditioning stimulus (CS) with an intensity between 50% and 90% of resting motor threshold (RMT) induces activation of GABAA inhibitory mechanisms observed as the SICI (inhibitory) effect on MEP amplitude. In contrast, if the CS intensity is above RMT, the SICF (excitatory) phenomenon can be present due to the superposition of D- and I-waves. Our aim was to investigate the dependence of inhibitory and facilitatory mechanisms on the orientation of the induced E-field of CS and TS. We developed a multi-locus TMS (mTMS) transducer, which allowed us to control the E-field orientation independently for CS and TS at a millisecond inter-pair interval (IPI). Eight healthy subjects (five males; mean age 29, range 21–35 years) participated in the study. mTMS was applied to the hotspot of the abductor pollicis brevis (APB) muscle in the left primary motor cortex. The stimulus intensities were based on the individual RMT of APB for PA and LM orientations. TS and single pulses were administered at 110% RMT. Twenty single pulses were applied for each TS orientation and for each of the 32 paired-pulse conditions. CS and TS stimuli were applied in every combination of the PA and LM orientations with four CS intensities (50, 70, 90, and 110% RMT) and two IPIs (1.5 and 2.7 ms) in a random order. Interaction between CS orientation, IPI, and CS intensity significantly affected TS MEP amplitudes. We observed no statistically significant difference between the responses induced by PA- and LM-oriented TS. CS at 70% RMT for SICI and at 110% RMT for SICF induced similar effects regardless of the TS orientation. We established that LM-oriented CS at 90% RMT produced a greater inhibition than stimuli at the same intensity in the PA orientation. Our results emphasize the minimal influence of the CS E-field dorientation on the test pulse. Additionally, we demonstrate the pivotal role of the stimulus intensity for any CS orientation. SICI and SICF evoked using perpendicular CS and TS directions indicate that we stimulated overlapping neuronal populations with both pulses.
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.