Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year)1. Minor cervical traumas, infection, migraine and hypertension are putative risk factors1, 2, 3, and inverse associations with obesity and hypercholesterolemia are described3, 4. No confirmed genetic susceptibility factors have been identified using candidate gene approaches5. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69–0.82; P = 4.46 × 10−10), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10−3; combined P = 1.00 × 10−11). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction6, 7, 8, 9. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.
Prior to 2010, medical care for people living with HIV/AIDS was provided at an outpatient facility near the center of St. Petersburg. Since then, HIV specialty clinics have been established in more outlying regions of the city. The study examined the effect of this decentralization of HIV care on patients' satisfaction with care in clinics of St. Petersburg, Russia. We conducted a cross-sectional study with 418 HIV-positive patients receiving care at the St. Petersburg AIDS Center or at District Infectious Disease Departments (centralized and decentralized models, respectively). Face-to-face interviews included questions about psychosocial characteristics, patient's satisfaction with care, and clinic-related patient experience. Abstraction of medical records provided information on patients' viral load. To compare centralized and decentralized models of care delivery, we performed bivariate and multivariate analysis. Clients of District Infectious Disease Departments spent less time in lines and traveling to reach the clinic, and they had stronger relationships with their doctor. The overall satisfaction with care was high, with 86% of the sample reporting high level of satisfaction. Nevertheless, satisfaction with care was strongly and positively associated with the decentralized model of care and Patient-Doctor Relationship Score. Patient experience elements such as waiting time, travel time, and number of services used were not significant factors related to satisfaction. Given the positive association of satisfaction with decentralized service delivery, it is worth exploring decentralization as one way of improving healthcare services for people living with HIV/AIDS.
Rigid amphipathic fusion inhibitors (RAFIs) are potent antivirals based on a perylene core linked with a nucleoside moiety. Sugar-free analogues of RAFIs, 5-(perylen-3-ylethynyl)uracil-1-acetic acid 1 and its amides 2, were synthesized using combined protection group strategy. Compounds 1 and 2 appeared to have low toxicity on porcine embryo kidney (PEK) or rhabdomiosarcoma (RD) cells together with remarkable activity against enveloped tick-borne encephalitis virus (TBEV): EC50 values vary from 0.077 mM to subnanomolar range. Surprisingly, 3-pivaloyloxymethyl (Pom) protected precursors 7 and 8 showed even more pronounced activity. All the compounds showed no activity against several nonenveloped enteroviruses, except 4-hydroxybutylamides 2d,g, which inhibited the reproduction of enterovirus A71 with EC50 50e100 mM, with a non-specific mode of action. The results suggest that the carbohydrate moiety of RAFI nucleosides does not play a crucial role in their antiviral action, and biological activity of the 5-(perylen-3-ylethynyl)uracil scaffold can be effectively modulated by substituents in positions 1 and 3. The high antiviral activity of these new compounds, coupled with low toxicity advocate their potential role in antiviral therapy.
Applying bootstrapped quantile regression to the Russian Longitudinal Monitoring Survey (RLMS) data, we examine the channels through which individuals experience and seek to cope with changes in consumption. We find that married individuals living in small households, with educated heads in urban areas are better equipped to smooth consumption. Investigating the impact of idiosyncratic shocks, we find that the labour market is an important transmission mechanism allowing households to smooth their consumption but also exposing them to risk, mainly through job loss. Outside of pension payments the formal social safety net does not facilitate consumption smoothing, thus heightening the importance of informal coping institutions. It transpires that both support from relatives/friends and home production act as important insurance mechanisms for the most vulnerable.
The cooperative dynamics of cellular populations emerging from the underlying interactions determines cellular functions and thereby their identity in tissues. Global deviations from this dynamics, on the other hand, reflect pathological conditions. However, how these conditions are stabilized from dysregulation on the level of the single entities is still unclear. Here, we tackle this question using the generic Hodgkin–Huxley type of models that describe physiological bursting dynamics of pancreatic -cells and introduce channel dysfunction to mimic pathological silent dynamics. The probability for pathological behavior in -cell populations is ~100% when all cells have these defects, despite the negligible size of the silent state basin of attraction for single cells. In stark contrast, in a more realistic scenario for a mixed population, stabilization of the pathological state depends on the size of the subpopulation which acquired the defects. However, the probability to exhibit stable pathological dynamics in this case is less than 10%. These results, therefore, suggest that the physiological bursting dynamics of a population of -cells is cooperatively maintained, even under intercellular communication defects induced by dysfunctional channels of single cells.
Diffusion imaging techniques such as DTI and HARDI are difficult to implement in infants because of their sensitivity to subject motion. A short acquisition time is generally preferred, at the expense of spatial resolution and signal-to-noise ratio. Before estimating the local diffusion model, most pre-processing techniques only register diffusion-weighted volumes, without correcting for intra-slice artifacts due to motion or technical problems. Here, we propose a fully automated strategy, which takes advantage of a high orientation number and is based on spherical-harmonics decomposition of the diffusion signal.Material and methods
The correction strategy is based on two successive steps: 1) automated detection and resampling of corrupted slices; 2) correction for eddy current distortions and realignment of misregistered volumes. It was tested on DTI data from adults and non-sedated healthy infants.Results
The methodology was validated through simulated motions applied to an uncorrupted dataset and through comparisons with an unmoved reference. Second, we showed that the correction applied to an infant group enabled to improve DTI maps and to increase the reliability of DTI quantification in the immature cortico-spinal tract.Conclusion
This automated strategy performed reliably on DTI datasets and can be applied to spherical single- and multiple-shell diffusion imaging.
Understanding neurocognitive mechanisms supporting the use of multiple languages is a key question in language science. Recent neuroimaging studies in monolinguals indicated that core language areas in human neocortex together with sensorimotor structures form a highly interactive system underpinning native language comprehension. While the experience of a native speaker promotes the establishment of strong action-perception links in the comprehension network, this may not necessarily be the case for L2 where, as it has been argued, the most a typical L2 speaker may get is a link between an L2 wordform and its L1 translation equivalent. Therefore, we investigated, whether the motor cortex of bilingual subjects shows differential involvement in processing action semantics of native and non-native words. We used high-density EEG to dynamically measure changes in the cortical motor system's activity, indexed by event-related desynchronisation (ERD) of the mu-rhythm, in response to passively reading L1 (German) and L2 (English) action words. Analysis of motor-related EEG oscillations at the sensor level revealed an early (starting ~150ms) and left-lateralised coupling between action and semantics during both L1 and L2 processing. Crucially, source-level activation in the motor areas showed that mu-rhythm ERD, while present for both languages, is significantly stronger for L1 words. This is the first neurophysiological evidence of rapid motor-cortex involvement during L2 action-semantic processing. Our results both strengthen embodied cognition evidence obtained previously in monolinguals and, at the same time, reveal important quantitative differences between L1 and L2 sensorimotor brain activity in language comprehension.
The review considers the roles cortisol (Crt), dehydroepiandrosterone (DHEA), and DHEA sul fate (DHEAS) play in the stress response. Agerelated, sexrelated, and circadian fluctuations in normal conditions and in acute or chronic stress are described for Crt, DHEA, and DHEAS. The main techniques used to estimate the Crt level in the blood, urine, and saliva are described, and approaches to the interpretation of the results discussed. Special attention is paid to Crt assays in anthropological and psychological studies.
Computer model coupled blood pressure dynamics in magisterial and small arteries networks and its stabilizing effect on heart functioning has been suggested. The Fermi-Pasta-Ulam auto recurrence in the description of the electrical activity of the heart has demonstrated the universal role of the FPU recurrence in the study of distributed dynamical systems. The heart electrical dynamics was described by the coupled Van der Pol differential equations with a time lag, linked with two additively coupled nonlinear differential equations circumscribing the blood pressure dynamics in the networks of magisterial and small arteries. The mathematical model developed by Yuen and Lake for description of the deep wave dynamics within the nonlinear Shrodinger (NSE) equation was used for description of the magisterial arterial blood pressure whereas for small arteries blood pressure dynamics was used the approach elaborated by Zabusky and Kruskal within the framework of the Korteveg de Vries (KdV) equation. The arterial blood pressure dynamics was interpreted as coupled FPU recurrences showing a rich variety of resulting FPU spectra, which were referred to different states of Cardio Vascular System. Synchronous registering of the real ECG and Pulse Wave Fourier dynamic images allowed to unify the characteristic Fourier pictures of the heart electrical activity with the hydrodynamic blood parameters developing in the networks of two types of arteries. The computer study of the suggested model and comparison of its results with the real data proved that the ECG Fourier parameters coupled with the Pulse Wave Fourier parameters form the FPU spectra that increase stability of Cardio Vascular System and can be used for diagnostics as well as for evaluation of the therapeutic arrangements results.
Background: Laminins are a major family of extracellular matrix proteins and the main component of basement membranes. Laminins are involved in many if not all stages of cancer progression, and expression of laminin genes has prognostic value in various types of cancer, including colorectal. Only single laminin genes or components of a single laminin trimer with significant differential expression have been regarded as potential biomarkers to date.
Results: Here we compared prognostic power of classifiers constructed from sets of laminin genes with that of any single laminin gene. The analysis showed that cumulative prognostic power of sets of laminin genes was higher and was achieved already with pairs and triples of the genes. Interestingly, components of the pairs and the triples did not belong to any known laminin trimer, but, taken together with the gene weights, suggested higher LAMA4/ LAMA5 expression ratio in patients with poor prognosis.
Conclusions: Analysis of the laminin expression profile rather than expression of the single genes or components of laminin trimers is useful for colorectal cancer prognosis in patients. High LAMA4/LAMA5 ratio is associated with increased permeability of basement membranes suggesting that basement membranes produced by colorectal tumors might be an important hindrance to their own dissemination in patients.
The paper is devoted to analysis of the debates on sex education in the Russian press. ‘Risk narrative structure’ of media articles on sex education was determined. This structure represents a system of mutually constituting elements, which include object of risk, risks themselves, solutions to their prevention, solutions opponents, and type of society these solutions presuppose. It is argued that analysis of risks with the aid of ‘risk narrative structures’ can be a useful development of sociocultural theory of risk, as competing risk narratives can befully grasped only when considered not as discrete claims about different ‘risks’ but as coherent systems of interrelated meanings. On the basis of this structure, competent risk media narratives of proponents and opponents of sex education were reconstructed. In these narratives different definitions of ‘children’ as objects of risk were constructed, and so were types of risks, and types of society. It would be oversimplifying to consider debates on sex education as a battle of ‘enlightened rationality’ against ‘dark irrationality.’ In each risk narrative the solution (introduction or ban of sex education) is a logically following element in the respective risk narrative. While sex education advocates were concerned about negative consequences of children’s sexual behaviour and defence of the ‘civilised society’s moral boundaries, the opposite side was concerned about retaining children’s moral purity and defence of ‘traditional’ moral boundaries.
A neural expert network system for diagnostis and prognosis of cardiovascular diseasas was developed.
Objectives: Development of a mathematical model and its implementation as a computer program for diagnostics and prediction of progression of the most widespread cardiovascular diseases; the program is to model different variants of disease progression for an observed patient, and to select individual recommendations for correction of his or her lifestyle, regimen and diet. Methods: Combination of technologies of neural networks and expert systems with a resulting synergistic effect. Results and Conclusion: Investigations of the developed mathematical model showed that it is able to reveal new knowledge which is yet unknown to medical science. In the course of software experiments performed by means of a diagnostics-and-prediction system, we revealed the facts showing that modern medical practice patterns of giving one and the same recommendations to all the cardiac patients without exception (including keeping to a hypocholesteric diet, giving up pernicious habits, limiting coffee and alcoholic drinks, losing weight and limiting intellectual and physical activity) are not always correct. Our investigations showed that some of these recommendations are not just unhealthy, but harmful for a number of patients. The neuro-expert diagnostics-and-prediction system presented in this paper allows doctors to reveal such non-typical patients and to develop individual recommendations especially for them.
A recent article in the Lancet, by David Stuckler, Larry King and Martin McKee,
investigated anew the fluctuations in adult male mortality rates that have come to
characterise the so-called post-communist mortality crisis. Adopting a cross-country,
time-series perspective the authors examined how the economic policy strategies of the
1990s impacted upon observed fluctuations in mortality. They conclude that the adoption
of a strategy of rapid (mass) privatisation contributed to the adverse mortality trends. We
subject that finding to closer scrutiny using the same data from which the Stuckler et al
claim stems. We find that their claim that mass privatisation adversely affected male
mortality trends in the post-Communist world does not stand up to closer examination. It
is not supported empirically and is at odds with what we know about both transition in
the post-communist world and about health trends over time in this region.
There is growing evidence that verbs are more difficult to processes than nouns (Cappa & Perani, 2002) and that verb retrieval is more commonly affected in aphasia compared to nouns (Jonkers & Bastiaanse, 1998). However, existing observations are largely based on naming and semantic judgment tasks. We investigate whether this processing difficulty is modality general. In this study for the first time we directly compare difficulty of comprehension of verbs versus nouns in Russian in individuals with and without aphasia using a novel instrument – a single-word comprehension test presented on a tablet.
The endogenous opioid system (EOS) controls the processing of nociceptive stimuli and is a pharmacological target for opioids. Alterations in expression of the EOS genes under neuropathic pain condition may account for low efficacy of opioid drugs. We here examined whether EOS expression patterns are altered in the lumbar spinal cord of the rats with spinal nerve ligation (SNL) as a neuropathic pain model. Effects of the left- and right-side SNL on expression of EOS genes in the ipsi- and contralateral spinal domains were analysed. The SNL-induced changes were complex and different between the genes; between the dorsal and ventral spinal domains; and between the left and right sides of the spinal cord. Prodynorphin (Pdyn) expression was upregulated in the ipsilateral dorsal domains by each the left and right-side SNL, while changes in expression of μ-opioid receptor (Oprm1) and proenkephalin (Penk) genes were dependent on the SNL side. Changes in expression of the Pdyn and κ-opioid receptor (Oprk1) genes were coordinated between the ipsi- and contralateral sides. Withdrawal response thresholds, indicators of mechanical allodynia correlated negatively with Pdyn expression in the right ventral domain after right side SNL. These findings suggest multiple roles of the EOS gene products in spinal sensitization and changes in motor reflexes, which may differ between the left and right sides.
Over the past half century the global tendency for improvements in longevity has been uneven across countries. This has resulted in widening of inter-country disparities in life expectancy. Moreover, the pattern of divergence appears to be driven in part by processes at the level of country groupings defined in geopolitical terms. A systematic quantitative analysis of this phenomenon has not been possible using demographic decomposition approaches as these have not been suitably adapted for this purpose. In this paper we present an elaboration of conventional decomposition techniques to provide a toolkit for analysis of the inter-country variance, and illustrate its use by analyzing trends in life expectancy in developed countries over a 40-year period.
We analyze trends in the population-weighted variance of life expectancy at birth across 36 developed countries and three country groups over the period 1970–2010. We have modified existing decomposition approaches using the stepwise replacement algorithm to compute age components of changes in the total variance as well as variance between and within groups of Established Market Economies (EME), Central and Eastern Europe (CEE), and the Former Soviet Union (FSU). The method is generally applicable to the decomposition of temporal changes in any aggregate index based on a set of populations.
The divergence in life expectancy between developed countries has generally increased over the study period. This tendency dominated from the beginning of 1970s to the early 2000s, and reversed only after 2005. From 1970 to 2010, the total standard deviation of life expectancy increased from 2.0 to 5.6 years among men and from 1.0 to 3.6 years among women. This was determined by the between-group effects due to polarization between the EME and the FSU. The latter contrast was largely fueled by the long-term health crisis in Russia. With respect to age, the increase in the overall divergence was attributable to between-country differences in mortality changes at ages 15–64 years compared to those aged 65 and older. The within-group variance increased, especially among women. This change was mostly produced by growing mortality differences at ages 65 and older.
From the early 1970s to the mid-2000s, the strong divergence in life expectancy across developed countries was largely determined by the between-group variance and mortality polarization linked to the East–West geopolitical division.
N-Methyl-D-aspartate receptors (NMDAr) are involved in multiple physiological functions and neuropsychiatric disorders. Dizocilpine (commonly referred to as MK-801) is a well-known non-competitive NMDAr antagonist with psychotomimetic properties. A combination of electrophysiological and molecular analyses reveals not only the synchrony of baseline oscillations by MK-801, but also more importantly new insight into differential gene expressions in the cerebral cortex, midbrain, hippocampus, ventral striatum, amygdala, and hypothalamus regions after acute low-dose (0.08 mg/kg) MK-801 treatment; only the ventral striatum showed increased gene expression at a high dose (0.16 mg/kg) of MK-801. We believe that our present study will contribute in the understanding of the pathogenic mechanisms of neuropsychiatric disorders.
Deep generative adversarial networks (GANs) are the emerging technology in drug discovery and biomarker development. In our recent work, we demonstrated a proof-of-concept of implementing deep generative adversarial autoencoder (AAE) to identify new molecular fingerprints with predefined anticancer properties. Another popular generative model is the variational autoencoder (VAE), which is based on deep neural architectures. In this work, we developed an advanced AAE model for molecular feature extraction problems, and demonstrated its advantages compared to VAE in terms of (a) adjustability in generating molecular fingerprints; (b) capacity of processing very large molecular data sets; and (c) efficiency in unsupervised pretraining for regression model. Our results suggest that the proposed AAE model significantly enhances the capacity and efficiency of development of the new molecules with specific anticancer properties using the deep generative models.