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.
MiRNAs are essential mediators of many biological processes. The aim of this study was to investigate the dynamics of miRNA-mRNA regulatory networks during exercise and the subsequent recovery period.
Here we monitored the transcriptome changes using microarray analysis of the whole blood of eight highly trained athletes before and after 30 min of moderate exercise followed by 30 min and 60 min of recovery period. We combined expression profiling and bioinformatics and analysed metabolic pathways enriched with differentially expressed mRNAs and mRNAs which are known to be validated targets of differentially expressed miRNAs. Finally we revealed four dynamically regulated networks comprising differentially expressed miRNAs and their known target mRNAs with anti-correlated expression profiles over time. The data suggest that hsa-miR-21-5p regulated TGFBR3, PDGFD and PPM1L mRNAs. Hsa-miR-24-2-5p was likely to be responsible for MYC andKCNJ2 genes and hsa-miR-27a-5p for ST3GAL6. The targets of hsa-miR-181a-5p included ROPN1L and SLC37A3. All these mRNAs are involved in processes highly relevant to exercise response, including immune function, apoptosis, membrane traffic of proteins and transcription regulation.
We have identified metabolic pathways involved in response to exercise and revealed four miRNA-mRNA networks dynamically regulated following exercise. This work is the first study to monitor miRNAs and mRNAs in parallel into the recovery period. The results provide a novel insight into the regulatory role of miRNAs in stress adaptation.
The performance of the three methods depends on the amount of averaged trials. Moreover, differences are found on both amplitude and latency of ERP components recorded in two environments (0 T vs 3 T). We showed that, while ERPs can be extracted from simultaneous EEG–fMRI data at 3 T, the static magnetic field might affect the physiological processes under investigation.The reproducibility of the ERPs in different recording environments (0 T vs 3 T) is a relevant issue that deserves further investigation to clarify the equivalence of cognitive processes in both behavioral and imaging studies.
The processing of sound changes and involuntary attention to them has been widely studied with event-related brain potentials (ERPs). Recently, functional magnetic resonance imaging (fMRI) has been applied to determine the neural mechanisms of involuntary attention and the sources of the corresponding ERP components. The gradient-coil switching noise from the MRI scanner, however, is a challenge to any experimental design using auditory stimuli. In the present study, the effects of MRI noise on ERPs associated with preattentive processing of sound changes and involuntary switching of attention to them were investigated. Auditory stimuli consisted of frequently presented “standard” sounds, infrequent, slightly higher “deviant” sounds, and infrequent natural “novel” sounds. The standard and deviant sounds were either sinusoidal tones or musical chords, in separate stimulus sequences. The mismatch negativity (MMN) ERP associated with preattentive sound change detection was elicited by the deviant and novel sounds and was not affected by the prerecorded background MRI noise (in comparison with the condition with no background noise). The succeeding positive P3a ERP responses associated with involuntary attention switching elicited by novel sounds were also not affected by the MRI noise. However, in ERPs to standard tones and chords, the P1, N1, and P2 peak latencies were significantly prolonged by the MRI noise. Moreover, the amplitude of the subsequent “exogenous” N2 to the standard sounds was significantly attenuated by the presence of MRI noise. In conclusion, the present results suggest that in fMRI the background noise does not interfere with the imaging of auditory processing related to involuntary attention.
To test a novel social network HIV risk-reduction intervention for MSM in Russia and Hungary, where same-sex behavior is stigmatized and men may best be reached through their social network connections.DESIGN:
A two-arm trial with 18 sociocentric networks of MSM randomized to the social network intervention or standard HIV/STD testing/counseling.SETTING:
St. Petersburg, Russia and Budapest, Hungary.PARTICIPANTS:
Eighteen 'seeds' from community venues invited the participation of their MSM friends who, in turn, invited their own MSM friends into the study, a process that continued outward until eighteen three-ring sociocentric networks (mean size = 35 members, n = 626) were recruited.INTERVENTION:
Empirically identified network leaders were trained and guided to convey HIV prevention advice to other network members.MAIN OUTCOME AND MEASURES:
Changes in sexual behavior from baseline to 3-month and 12-month follow-up, with composite HIV/STD incidence, measured at 12 months to corroborate behavior changes.RESULTS:
There were significant reductions between baseline, first follow-up, and second follow-up in the intervention versus comparison arm for proportion of men engaging in any unprotected anal intercourse (UAI) (P = 0.04); UAI with a nonmain partner (P = 0.04); and UAI with multiple partners (P = 0.002). The mean percentage of unprotected anal intercourse acts significantly declined (P = 0.001), as well as the mean number of UAI acts among men who initially had multiple partners (P = 0.05). Biological HIV/STD incidence was 15% in comparison condition networks and 9% in intervention condition networks.CONCLUSION:
Even where same-sex behavior is stigmatized, it is possible to reach MSM and deliver HIV prevention through their social networks.
The effects of functional magnetic resonance imaging (fMRI) acoustic noise were investigated on the parameters of event-related responses (ERPs) elicited during auditory matching-to-sample location and pitch working memory tasks. Stimuli were tones with varying location (left or right) and frequency (high or low). Subjects were instructed to memorize and compare either the locations or frequencies of the stimuli with each other. Tape-recorded fMRI acoustic noise was presented in half of the experimental blocks. The fMRI noise considerably enhanced the P1 component, reduced the amplitude and increased the latency of the N1, shortened the latency of the N2, and enhanced the amplitude of the P3 in both tasks. The N1 amplitude was higher in the location than pitch task in both noise and no-noise blocks, whereas the task-related N1 latency difference was present in the no-noise blocks only. Although the task-related differences between spatial and nonspatial auditory responses were partially preserved in noise, the finding that the acoustic gradient noise accompanying functional MR imaging modulated the auditory ERPs implies that the noise may confound the results of auditory fMRI experiments especially when studying higher cognitive processing
Optimal choice of glucocorticoids (GC), like dexamethasone (DEXA) vs (methyl)prednisolone (MePRED) for remission induction in childhood acute lymphoblastic leukemia (ALL) remains controversial. The favorable antileukemic efficacy of DEXA is off-set by its dose-limiting toxicity. Hence, one objective of trial ALL-Moscow/Berlin (MB) 2002 was to evaluate whether an equiactive dose of MePRED leads to superior event-free survival (EFS) rates by reducing mortality, while maintaining the low relapse rates and central nervous system (CNS) protection obtained with DEXA previously. Of 1163 pediatric patients with newly diagnosed B-cell precursor or T-cell ALL, 1064 were randomized to induction with either 6 mg/m^2 DEXA (n=539) or 60mg/m^2 MePRED(n=525).
Background Timely assessment of HIV/AIDS burden is essential for policy-setting and program evaluation. Based on the Global Burden of Disease study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, ART coverage and mortality for 195 countries and territories from 1980 to 2015. Methods For countries without high quality vital registration data, we estimated prevalence and incidence from antenatal clinic data and population-based sero-prevalence surveys and assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates, on and off antiretroviral therapy mortality (ART), and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. Estimation of incidence, prevalence and death uses GBD versions of the EPP and Spectrum software originally developed by UNAIDS. These versions have been recoded for speed and use updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high quality vital registration data, we developed the Cohort Incidence Bias Adjustment model to estimate HIV incidence and prevalence largely from the number of deaths due to HIV recorded in cause of death statistics. Cause of death statistics have been corrected for garbage coding and HIV misclassification. Findings Globally, HIV incidence reached its peak in 1997 at 3.3 million. Annual incidence has stayed relatively constant at about 2.5 million since 2005 after a period of faster decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38.8 million in 2015. At the same time, mortality due to HIV/AIDS has been declining at a steady pace from its peak at 1.8 million deaths in 2005 to 1.2 million deaths in 2015. There is substantial heterogeneity in the levels and trends of HIV/AIDS across countries. While success stories can be found in many countries with improved mortality due to HIV/AIDS and declines in annual new infections, slowdowns or increases in rate of change in annual new infections has been observed elsewhere. Manuscript Interpretation The global scale-up of ART and PMTCT has been one of the great successes of global health in the last two decades. In the last decade, progress reducing new infections has been very slow, development assistance for health devoted to HIV has stagnated, and low-income country resources for health have grown slowly. New ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90- 90 UNAIDS targets will be hard to achieve
Fragmentation in organization and discontinuities in the provision of medical care are problems in all health systems. A major challenge is to strengthen integration in order to enhance efficiciency and health outcomes. This artickle assesses issues related to fragmentation and integration in concptual terms and argues that key attributes of integration are teamwork, coordination and continuity of care. It then presents a summary of service integration problems in Russia and the results of a large survey of physicians concerning the attributes of integration. It is argued that characteristics of the national service delivery model don't ensure integration. Teh Senashko model is not an equivalent to the integrated model. Big organizational forms of service provision, like polyclinics and integrated hospitals-polyclinics don't have higher scores of integration indicators than smaller ones. Proposals to improve integration in Russia are presented with the focus on the regular evaluation of integration/fragmentation, regulation of integration activities, enhancing the role of PHC providers, economic incentives.
A large body of evidence indicates modified expression of protein-coding genes in response to different kinds of physical activity. Recent years have exposed another level of regulation of cellular processes mediated by non-coding RNAs. MicroRNAs (miRNAs) are one of the largest families of non-coding RNAs. MiRNAs mediate post-transcriptional regulation of gene expression. The amount of data supporting the key role of miRNAs in the adaptation of the immune and other body systems to exercise steadily grows. MiRNAs change their expression profiles after exercise and seem to be involved in regulation of exercise-responsive genes in immune and other cell types. Here we discuss existing data and future directions in the field.
How do human brain networks react to dynamic changes in the sensory environment? We measured rapid changes in brain network organization in response to brief, discrete, salient auditory stimuli. We estimated network topology and distance parameters in the immediate central response period, <1 s following auditory presentation of standard tones interspersed with occasional deviant tones in a mismatch-negativity (MMN) paradigm, using magnetoencephalography (MEG) to measure synchronization of high-frequency (gamma band; 33-64 Hz) oscillations in healthy volunteers. We found that global small-world parameters of the networks were conserved between the standard and deviant stimuli. However, surprising or unexpected auditory changes were associated with local changes in clustering of connections between temporal and frontal cortical areas and with increased interlobar, long-distance synchronization during the 120- to 250-ms epoch (coinciding with the MMN-evoked response). Network analysis of human MEG data can resolve fast local topological reconfiguration and more long-range synchronization of high-frequency networks as a systems-level representation of the brain's immediate response to salient stimuli in the dynamically changing sensory environment.
Status epilepticus (SE) provokes changes, which lead to neuronal alterations. Endocannabinoids (eCBs) can affect the neuronal survival during excitotoxicity and brain damage. Using a kainic acid (KA)-induced experimental SE model, we investigated whether cellular changes entail damage to endoplasmic reticulum (ER), mitochondria, and nuclei in hippocampal cells (CA1 field), and whether these alterations can be diminished by treatment with URB597, an inhibitor of eCB enzymatic degradation.
Material and methods
SE was induced in Wistar rats by the microinjection of KA into the lateral ventricle. URB597 or a vehicle (10% DMSO) were injected in the same way into the brain of animals 24 h after the KA infusion and then daily for the next nine days. The behavior of animals was controlled visually and recorded with a video system. The intensity of SE significantly varied in different animals. Convulsive (stages 3–5 according to the Racine scale) and nonconvulsive seizures (mainly stages 1, 2 and rarely 3, 4) were recognized.
Two weeks after SE, a significant loss of hippocampal cells occurred in animals with KA injections. In survived cells, ultrastructural alterations in ER, mitochondria, and nuclei of hippocampal neurons were observed. The degree of cell injury depended on the severity of SE. Alterations evoked by moderate seizures were prevented or diminished by URB597, but strong seizures induced mostly irreversible damage.
The beneficial impact of the FAAH inhibitor URB597 can give impetus to the development of novel neuroprotective strategies.
The paper deals with the Forrester’s approach to analysis of heart electrical dynamics based on the hypothesis that heart belongs to the class of Complex Systems and its dynamics can be described by coupled Van der Pol differential equations with a time lag. The chain of such equations suggested by Ginzburg and Landau was used to describe such states of heart dynamics as normal beatings, fibrillation and ischemia through the kinds of the chain dynamics as regular oscillations, chaotic dynamics and intermittency dynamics of order – disorder type correspondingly. The mathematical model supporting the hypothesis demonstrated all mentioned model modes of heart functioning. During the computer, study of the model another hypothesis has been put forward concerning the existence in the heart dynamics a special oscillatory region, which interacts with ischemia oscillatory region lowering its energy. According to the prediction, both regions had to have different resonant parameters. Taking into account the results of the model study there has been made another prediction about possible synchronization of the heartbeats by applying external periodical perturbation at frequency of about 1 Hz. The pilot data supporting the proposed hypothesis have demonstrated the reality of the suggested hypothesis. In particular, the real ECG and their Fourier spectra of healthy patients corresponded to the model regular ECG and their Fourier spectra. The ECG Fourier spectrum of the patient with a cardio stimulator corresponded to the model synchronization of the ECG and its Fourier spectrum generated by the developed mathematical model. As far as the ECGs and Fourier spectra in patients with differently developed ischemia are concerned, they confirmed the hypothesis about the existing of two interacting oscillatory regions in myocardium: the ischemic and the defending ones. The defending region decreases the volume of the ischemic process through lowering its energy. Summing it up one can conclude that the experimental results confirmed the suggested hypothesis and the prediction following from it.