Different environmental factors (i.e., toxins, heavy metals, ultraviolet (UV) rays, and X-radiation) cause damage to DNA, cell membranes and other organelles and induce oxidative stress, which results in the excessive production of reactive oxygen species (ROS) by phagocytes. All types of cell stress are accompanied by the activation of anti-stress genes that can suppress ROS synthesis. We hypothesized that different environmental factors would affect organisms through the activation of anti-stress genes by autologous serum (AS) proteins, followed by the synthesis of molecules that increase cell resistance to oxidative stress. The goal of this work was to study the influence of AS on ROS production by peripheral blood neutrophils isolated from donors in different age groups. Neutrophils were isolated from 59 donors (38-94 years old). AS was heated at 100°C for 30 s. or irradiated by UV light at 200-280 nm and 8 W for 10 min. Neutrophils were exposed to heat shock at 42°C for 1 min. (short-term heating stress) or 43°C for 10 min., followed by the determination of the chemiluminescence reaction induced by zymosan. AS can increase or decrease ROS production by neutrophils depending on the structure of the proteins in the serum; these structures can be changed by heating or UV treatment and the temperature of their interaction (4 or 37°C). We propose that the effect of environmental factors on AS proteins can cause an adverse increase in oxidative stress levels due to the functional reduction of anti-stress genes. We found a negative correlation between the quantity of intracellular Hsp70 and levels of intracellular ROS production following 10 min of heat shock at 43°C. Short-term heating stress (1 min) at 42°C was followed by a prominent reduction in ROS production. This effect may be a result of the impact of the hormone adrenaline on the functions of anti-stress genes. Indeed, the same effect was observed after treatment of the neutrophils with adrenaline at concentrations of 10-4 and 10-5 M. In contrast, dexamethasone from the other stress hormone group did not evoke the same effect at the same concentrations. © 2015 Semenkov, Michalski and Sapozhnikov.
PWID were recruited using respondent-driven sampling (RDS) in eight Russian cities. A standardized survey was administered to collect sociodemographic and behavioral information. Blood specimens were obtained for serological testing for HCV and HIV-1. Data across the eight sites were pooled to identify individual-, network-, and city-level factors associated with positive HCV serostatus.
Among 2,596 PWID participating in the study, 1,837 tested positive for HCV (71%). The sample was 73% male and the mean age was 28. Very few PWID reported regular contact with harm reduction programs. Factors associated with testing positive for HCV were longer duration of injection drug use, testing positive for HIV-1, sharing non-syringe injection paraphernalia and water for rinsing syringes, and larger social network size. Factors negatively associated with HCV-positive serostatus were injecting with a used syringe and two city-level factors: longer mean RDS recruitment chain in a city and higher levels of injecting stimulants.
HCV prevalence in all eight Russian cities is at the higher end of the range of HCV prevalence among PWID in Europe, which provides evidence that more resources, better prevention programs, and accelerated treatment targeting PWID are needed to control the HCV epidemic.
A part of the auditory system automatically detects changes in the acoustic environment. This preattentional process has been studied extensively, yet its cerebral origins have not been determined with sufficient accuracy to allow comparison to established anatomical and functional parcellations. Here we used event-related functional MRI and EEG in a parametric experimental design to determine the cortical areas in individual brains that participate in the detection of acoustic changes. Our results suggest that automatic change processing consists of at least three stages: initial detection in the primary auditory cortex, detailed analysis in the posterior superior temporal gyrus and planum temporale, and judgment of sufficient novelty for the allocation of attentional resources in the mid-ventrolateral prefrontal cortex.
High-definition transcranial direct current stimulation (HD-tDCS) is a novel brain stimulation method that has high potential for use in language therapy for speakers with aphasia, due to its safety and focality. This study aimed to obtain foundational data on using HD-tDCS to modulate language processing in healthy speakers. Participants received stimulation either of Broca’s area or of the left angular gyrus (20 min of anodal, cathodal, and sham stimulation on separate days), followed by naming and lexical decision tasks with single-word verb and noun stimuli. We found that cathodal stimulation over both Broca’s area and the left angular gyrus increased naming speed for both verbs and nouns, challenging the traditional view of cathodal stimulation as suppressive or leading to decreased performance. The effect did not extend to the lexical decision task. Additionally, effects of specific stimulation types depended on the order of their administration, suggesting possible physiological carry-over and/or task novelty effects. These results are relevant to the application of HD-tDCS to enhance and direct neural plasticity in patients with neurogenic language disorders.
Genes with significant differential expression are traditionally used to reveal the genetic background underlying phenotypic differences between cancer cells. We hypothesized that informative marker sets can be obtained by combining genes with a relatively low degree of individual differential expression. We developed a method for construction of highly informative gene combinations aimed at the maximization of the cumulative informative power and identified sets of 2–5 genes efficiently predicting recurrence for ER-positive breast cancer patients. The gene combinations constructed on the basis of microarray data were successfully applied to data acquired by RNA-seq. The developed method provides the basis for the generation of highly efficient prognostic and predictive gene signatures for cancer and other diseases. The identified gene sets can potentially reveal novel essential segments of gene interaction networks and pathways implied in cancer progression.
Quantification and normalization of RT-qPCR data critically depends on the expression of so called reference genes. Our goal was to develop a strategy for the selection of reference genes that utilizes microarray data analysis and combines known approaches for gene stability evaluation and to select a set of appropriate reference genes for research and clinical analysis of breast samples with different receptor and cancer status using this strategy.
A preliminary search of reference genes was based on high-throughput analysis of microarray datasets. The final selection and validation of the candidate genes were based on the RT-qPCR data analysis using several known methods for expression stability evaluation: comparative ∆Ct method, geNorm, NormFinder and Haller equivalence test.
A set of five reference genes was identified: ACTB, RPS23, HUWE1, EEF1A1 and SF3A1. The initial selection was based on the analysis of publically available well-annotated microarray datasets containing different breast cancers and normal breast epithelium from breast cancer patients and epithelium from cancer-free patients. The final selection and validation were performed using RT-qPCR data from 39 breast cancer biopsy samples. Three genes from the final set were identified by the means of microarray analysis and were novel in the context of breast cancer assay. We showed that the selected set of reference genes is more stable in comparison not only with individual genes, but also with a system of reference genes used in commercial OncotypeDX test.
A selection of reference genes for RT-qPCR can be efficiently performed by combining a preliminary search based on the high-throughput analysis of microarray datasets and final selection and validation based on the analysis of RT-qPCR data with a simultaneous examination of different expression stability measures. The identified set of reference genes proved to be less variable and thus potentially more efficient for research and clinical analysis of breast samples comparing to individual genes and the set of reference genes used in OncotypeDX assay.
This article is based on the results of research into the professional status and professionalisation of homeopathy in Russia. The theoretical framework is based on the connection of concepts such as social closure, autonomy and professionalisation, which accords to the Anglo-Saxon tradition of studying professions. This framework helps analyze some of the parameters of professional homeopaths’ status, namely the economic, power-related and socio-cultural aspects. The examination is based on qualitative and quantitative data obtained from semi-structured interviews with homeopaths and a survey conducted by the author at the Annual Moscow Conference of Homeopathy as well as information gained in the course of the secondary data analysis. The survey was used, in part, to clarify and add to the questions that had arisen in the interviews. In order to define the level of individual autonomy among homeopaths we developed quantitative indicators. The data demonstrates that the economic status of Russian homeopathy specialists is relatively low, that professional associations play a limited role in the self-regulation of the group, and that the mechanisms of social closure are weak. All this hinders homeopaths’ professionalisation. Nonetheless, homeopaths find a sufficiently high level of individual autonomy as homeopathic practice is not strictly standardised. Today homeopaths as a group face the choice between two professionalisation strategies. One offers the standardisation of homeopathy, which will allow it to better integrate into conventional medicine but threatens ordinary homeopathy practices with a loss of autonomy. Another strategy proposes the rejection of standardisation and integration, instead focusing on the preservation of the unique identity and autonomy of the practice. The choice to move in one direction or the other is a dilemma for homeopaths as each option possesses its own advantages and restrictions.
The Russian health care system retains the main characteristics of medical care delivery in the Soviet Union. However the transition from socialism to capitalism in the 90s and the economic growth in the 2000s had a significant impact on accessibility of medical care.
OBJECTIVE: Despite the long history of digital radiology, one of its most critical aspects-information security-still remains extremely underdeveloped and poorly standardized. To study the current state of radiology security, we explored the worldwide security of medical image archives. MATERIALS AND METHODS: Using the DICOM data-transmitting standard, we implemented a highly parallel application to scan the entire World Wide Web of networked computers and devices, locating open and unprotected radiology servers. We used only legal and radiology-compliant tools. Our security-probing application initiated a standard DICOM handshake to remote computer or device addresses, and then assessed their security posture on the basis of handshake replies. RESULTS: The scan discovered a total of 2774 unprotected radiology or DICOM servers worldwide. Of those, 719 were fully open to patient data communications. Geolocation was used to analyze and rank our findings according to country utilization. As a result, we built maps and world ranking of clinical security, suggesting that even the most radiology-advanced countries have hospitals with serious security gaps. CONCLUSION: Despite more than two decades of active development and implementation, our radiology data still remains insecure. The results provided should be applied to raise awareness and begin an earnest dialogue toward elimination of the problem. The application we designed and the novel scanning approach we developed can be used to identify security breaches and to eliminate them before they are compromised. © American Roentgen Ray Society.
Perceptual decisions not only depend on the incoming information from sensory systems but constitute a combination of current sensory evidence and internally accumulated information from past encounters. Although recent evidence emphasizes the fundamental role of prior knowledge for perceptual decision making, only few studies have quantified the relevance of such priors on perceptual decisions and examined their interplay with other decision-relevant factors, such as the stimulus properties. In the present study we asked whether hysteresis, describing the stability of a percept despite a change in stimulus property and known to occur at perceptual thresholds, also acts as a form of an implicit prior in tactile spatial decision making, supporting the stability of a decision across successively presented random stimuli (i.e., decision hysteresis). We applied a variant of the classical 2-point discrimination task and found that hysteresis influenced perceptual decision making: Participants were more likely to decide 'same' rather than 'different' on successively presented pin distances. In a direct comparison between the influence of applied pin distances (explicit stimulus property) and hysteresis, we found that on average, stimulus property explained significantly more variance of participants' decisions than hysteresis. However, when focusing on pin distances at threshold, we found a trend for hysteresis to explain more variance. Furthermore, the less variance was explained by the pin distance on a given decision, the more variance was explained by hysteresis, and vice versa. Our findings suggest that hysteresis acts as an implicit prior in tactile spatial decision making that becomes increasingly important when explicit stimulus properties provide decreasing evidence.
Background Reliable and comparable data on causes of death are crucial for public health analysis, but the usefulness of these data can be markedly diminished when the approach to coding is not standardized across territories and/or over time. Because the Russian system of producing information on causes of death is highly decentralized, there may be discrepancies in the coding practices employed across the country. In this study, we evaluate the uniformity of cause-of-death coding practices across Russian regions using an indirect method. Methods Based on 2002–2012 mortality data, we estimate the prevalence of the major causes of death (70 causes) in the mortality structures of 52 Russian regions. For each region-cause combination we measured the degree to which the share of a certain cause in the mortality structure of a certain region deviates from the respective inter-regional average share. We use heat map visualization and a regression model to determine whether there is regularity in the causes and the regions that is more likely to deviate from the average level across all regions. In addition to analyzing the comparability of cause-specific mortality structures in a spatial dimension, we examine the regional cause-of-death time series to identify the causes with temporal trends that vary greatly across regions. Results A high level of consistency was found both across regions and over time for transport accidents, most of the neoplasms, congenital malformations, and perinatal conditions. However, a high degree of inconsistency was found for mental and behavioral disorders, diseases of the nervous system, endocrine disorders, ill-defined causes of death, and certain cardiovascular diseases. This finding suggests that the coding practices for these causes of death are not uniform across regions. The level of consistency improves when causes of death can be grouped into broader diagnostic categories. Conclusion This systematic analysis allows us to present a broader picture of the quality of cause-of-death coding at the regional level. For some causes of death, there is a high degree of variance across regions in the likelihood that these causes will be chosen as the underlying causes. In addition, for some causes of death the mortality statistics reflect the coding practices, rather than the real epidemiological situation.
Background: Krokodil is an informal term for a cheap injectable illicit drug domestically prepared from codeine-containing medication (CCM). The method of krokodil preparation may produce desomorphine as well as toxic reactants that cause extensive tissue necrosis. The first confirmed report of krokodil use in Russia took place in 2004. In 2012, reports of krokodil-related injection injuries began to appear beyond Russia in Western Europe and the United States.
Objective: This exploratory study had two main objectives: (1) to determine if Internet search patterns could detect regularities in behavioral responses to Russian CCM policy at the population level, and (2) to determine if complementary data sources could explain the regularities we observed.
Methods: First, we obtained krokodil-related search pattern data for each Russia subregion (oblast) between 2011 and 2012. Second, we analyzed several complementary data sources included krokodil-related court cases, and related search terms on both Google and Yandex to evaluate the characteristics of terms accompanying krokodil-related search queries.
Results: In the 6 months preceding CCM sales restrictions, 21 of Russia's 83 oblasts had search rates higher than the national average (mean) of 16.67 searches per 100,000 population for terms associated with krokodil. In the 6 months following restrictions, mean national searches dropped to 9.65 per 100,000. Further, the number of oblasts recording a higher than average search rate dropped from 30 to 16. Second, we found krokodil-related court appearances were moderately positively correlated (Spearman correlation=.506, P≤.001) with behaviors consistent with an interest in the production and use of krokodil across Russia. Finally, Google Trends and Google and Yandex related terms suggested consistent public interest in the production and use of krokodil as well as for CCM as analgesic medication during the date range covered by this study. Conclusions: Illicit drug use data are generally regarded as difficult to obtain through traditional survey methods. Our analysis suggests it is plausible that Yandex search behavior served as a proxy for patterns of krokodil production and use during the date range we investigated. More generally, this study demonstrates the application of novel methods recently used by policy makers to both monitor illicit drug use and influence drug policy decision making.
Building on long-term benefits of early intervention (Paper 2 of this Series) and increasing commitment to early childhood development (Paper 1 of this Series), scaled up support for the youngest children is essential to improving health, human capital, and wellbeing across the life course. In this third paper, new analyses show that the burden of poor development is higher than estimated, taking into account additional risk factors. National programmes are needed. Greater political prioritisation is core to scale-up, as are policies that afford families time and financial resources to provide nurturing care for young children. Effective and feasible programmes to support early child development are now available. All sectors, particularly education, and social and child protection, must play a role to meet the holistic needs of young children. However, health provides a critical starting point for scaling up, given its reach to pregnant women, families, and young children. Starting at conception, interventions to promote nurturing care can feasibly build on existing health and nutrition services at limited additional cost. Failure to scale up has severe personal and social consequences. Children at elevated risk for compromised development due to stunting and poverty are likely to forgo about a quarter of average adult income per year, and the cost of inaction to gross domestic product can be double what some countries currently spend on health. Services and interventions to support early childhood development are essential to realising the vision of the Sustainable Development Goals.
Most common drug development failures originate from either bioavailability problems, or unexpected toxic effects. The culprit is often the liver, which is responsible for biotransformation of a majority of xenobiotics. Liver may be modeled using "liver on a chip" devices, which may include established cell lines, primary human cells, and stem cell-derived hepatocyte-like cells. The choice of biological material along with its processing and maintenance greatly influence both the device performance and the resultant toxicity predictions. Impediments to the development of "liver on a chip" technology include the problems with standardization of cells, limitations imposed by culturing and the necessity to develop more complicated fluidic contours. Fortunately, recent breakthroughs in the development of cell-based reporters, including ones with fluorescent label, permits monitoring of the behavior of the cells embed into the "liver on a chip" devices. Finally, a set of computational approaches has been developed to model both particular toxic response and the homeostasis of human liver as a whole; these approaches pave a way to enhance the in silico stage of assessment for a potential toxicity.
On the web page of British medical Journal, the outpost of evidence based medicine (EBM) the voting collected 500 voices and 52% agreed that “EBM is broken” (as of June 22). Readers did vote in relation to the article, published by a group of EBM promoters 1. In this article, Trisha Greenhalgh et al. listed for the “Evidence Based Medicine Renaissance Group” number of problems with the development of the EBM practice. Despite successfully addressing these problems, the article call for the “Return to real evidence based medicine”. The call is addressed mostly to clinicians, but three points make it relevant for public health.
The study explores the so-called ‘Kyrgyz clinics’ and their place in the migrant infrastructure of Moscow, Russia. We focus on the unique status of these clinics specifically aimed at and tailored for the migrants’ medical and psychosocial needs. We have found that the role of Kyrgyz clinics is not limited to the provision of affordable medical services. It is a milieu where the migrant patients come with their problems to migrant doctors, and where they can use their native language and cultural code to talk about their health problems. In particular, Kyrgyz doctors at such clinics play the role of intermediaries between migrants and other medical institutions of Moscow, as migrants often lack information about budget healthcare services in Moscow. We also briefly outline how migrants use informal strategies and networks to overcome the barriers to receiving medical care.
Neuronal activity in the subthalamic nucleus (STN) of patients with Parkinson's disease (PD) is characterised by excessive neuronal synchronization, particularly in the beta frequency range. However, less is known about the temporal dynamics of neuronal oscillations in PD. In this respect long-range temporal correlations (LRTC) are of special interest as they quantify the neuronal dynamics on different timescales and have been shown to be relevant for optimal information processing in the brain. While the presence of LRTC has been demonstrated in cortical data, their existence in deep brain structures remains an open question. We investigated (i) whether LRTC are present in local field potentials (LFP) recorded bilaterally from the STN at wakeful rest in ten patients with PD after overnight withdrawal of levodopa (OFF) and (ii) whether LRTC can be modulated by levodopa treatment (ON). Detrended fluctuation analysis was utilised in order to quantify the temporal dynamics in the amplitude fluctuations of LFP oscillations. We demonstrated for the first time the presence of LRTC (extending up to 50 s) in the STN. Importantly, the ON state was characterised by significantly stronger LRTC than the OFF state, both in beta (13-35 Hz) and high-frequency (> 200 Hz) oscillations. The existence of LRTC in subcortical structures such as STN provides further evidence for their ubiquitous nature in the brain. The weaker LRTC in the OFF state might indicate limited information processing in the dopamine-depleted basal ganglia. The present results implicate LRTC as a potential biomarker of pathological neuronal processes in PD.
It is a common belief that the shift to digital imaging some 20 years ago helped medical image exchange and got rid of any potential image loss that was happening with printed image films. Unfortunately, this is not the case: despite the most recent advances in digital imaging, most hospitals still keep losing their imaging data, with these losses going completely unnoticed. As a result, not only does image loss affect the faith in digital imaging but it also affects patient diagnosis and daily quality of clinical work. This paper identifies the origins of invisible image losses, provides methods and procedures to detect image loss, and demonstrates modes of action that can be taken to stop the problem from happening.
Autism spectrum conditions (ASC) are characterised by deficits in understanding and expressing emotions and are frequently accompanied by alexithymia, a difficulty in understanding and expressing emotion words. Words are differentially represented in the brain according to their semantic category and these difficulties in ASC predict reduced activation to emotion-related words in limbic structures crucial for affective processing. Semantic theories view 'emotion actions' as critical for learning the semantic relationship between a word and the emotion it describes, such that emotion words typically activate the cortical motor systems involved in expressing emotion actions such as facial expressions. As ASC are also characterised by motor deficits and atypical brain structure and function in these regions, motor structures would also be expected to show reduced activation during emotion-semantic processing. Here we used event-related fMRI to compare passive processing of emotion words in comparison to abstract verbs and animal names in typically-developing controls and individuals with ASC. Relatively reduced brain activation in ASC for emotion words, but not matched control words, was found in motor areas and cingulate cortex specifically. The degree of activation evoked by emotion words in the motor system was also associated with the extent of autistic traits as revealed by the Autism Spectrum Quotient. We suggest that hypoactivation of motor and limbic regions for emotion-word processing may underlie difficulties in processing emotional language in ASC. The role that sensorimotor systems and their connections might play in the affective and social-communication difficulties in ASC is discussed.