Analysis of Changes in Microcirculation Parameters of Symmetrical Areas of the Human Head under Conditions of Hypoxic Influences.

The reactions of microcirculation parameters of symmetrical areas of the human head to hypoxic loads were studied. The study was conducted in 10 healthy male volunteers aged 18-19 years. Short-term hypoxia was modeled using a ReOxy Cardio normobaric device (S. A. Aimediq). Synchronous measurements of microcirculation parameters in symmetrical temporal regions of the head at the basal state and immediately after short-term hypoxic exposure were carried out by the method of laser Doppler flowmetry. We evaluated statistical characteristics of perfusion of both sides, as well as regression characteristics of the relationship between changes in the microcirculation parameters and the initial values of these parameters. It was shown that the reaction of the microcirculation parameters in symmetrical regions of the head to hypoxia depends on the initial microcirculation parameters in ipsi- and contralateral sides. 3D graphs were constructed and regression equations describing these relationships were formulated. A new method of geometric sensing is proposed, which allows predicting the direction of reactions to hypoxic effects. The obtained data illustrate the specificity of regulation of microcirculation of paired organs determined by the presence of functional asymmetry. A new method of geometric zoning is proposed, which allows solving the problems of personalized assessments of the state of the microcirculation system in patients.

Clinical activity of brigatinib in ROS1-rearranged non-small cell lung cancer.

BACKGROUND: Brigatinib is a potent ROS1 inhibitor. The existing data on its clinical activity in ROS1-rearranged non-small cell lung cancer (NSCLC) are limited to four cases. METHODS: Six patients with ROS1-rearranged advanced NSCLC treated with brigatinib were identified through search of the internal databases of four participating cancer centers. Four additional patients were selected by PubMed and Google Scholar search. The objective response rate (ORR), progression-free survival (PFS) (RECIST v.1.1), duration of treatment (DOT), and safety were assessed. RESULTS: Of eight patients evaluable for response assessment (crizotinib naive-1, crizotinib resistant -7), three patients demonstrated a partial response (ORR-37%). One crizotinib-naive patient had an ongoing response at 21.6 months. Of seven crizotinib-resistant patients, two patients demonstrated a partial response (ORR-29%), and one patient (14%) had stable disease. PFS, available in four crizotinib-resistant patients, was 7.6 + , 2.9, 2.0, and 0.4 months. In crizotinib-resistant patients, DOT was 9.7 + , 7.7 + , 7.6 + , 4.0, 2.0, 1.1, 0.4 months, and was not reported in two patients. Genomic profiling in one responder revealed no ROS1 alteration, suggesting that the response was attributable to "off-target" brigatinib activity. In two patients with progressive disease, genomic profiling demonstrated a cMET exon 14 mutation + KRAS G12A mutation in one case, and a persisting ROS1-CD74 fusion + TP53 K139N, FGFR2 E250G, ATM G2695D, and NF1 R2258Q mutations in the other. No grade 3-5 toxicity was observed. CONCLUSION: Brigatinib demonstrated modest activity in crizotinib-resistant ROS1-rearranged NSCLC. Its intracranial and systemic activity should be assessed in correlation with the underlying molecular mechanism of crizotinib resistance.

Our series is the first to describe brigatinib activity in ROS1-altered NSCLC. In crizotinib-resistant patients, ORR with brigatinib was 29%. PFS with brigatinib was 7.6+, 2.9, 2.0, and 0.4 months. DOT with brigatinib was 9.7+, 7.7+, 7.6+, 4.0, 2.0, 1.1, 0.4 months. The correlation between response and molecular resistance needs further exploration.

[Adaptation to dosed hypoxia-hyperoxia as a factor in improving the quality of life of elderly patients with cardiac pathology.]

In order to substantiate new approaches to maintain the quality of life of elderly patients with cardiac pathology, the current study is made to evaluate the effectiveness and safety of technology, based on the principles of adaptive medicine, the method of interval hypoxic-hyperoxic training (IHHT). It was proved the use of IHHT technology in elderly people with HIBS in the prescribed regime leads to a substantial increase in the subjective perception of the quality of life, their psycho-emotional status, the number of attacks of angina pectoris, which was accompanied by an increase in the level of physical working capacity, exercise tolerance, normalization of lipid and carbohydrate metabolism. Treatments by interval hypoxic-hyperoxic training are well tolerated, do not cause side effects; when developing optimal individualized regimens' principles IHHT can be used in the complex rehabilitation of elderly patients with cardiac and co-morbid pathology.

[Adaptation to Intermittent Hypoxia-Hyperoxia in the Rehabilitation of Patients With Ischemic Heart Disease: Exercise Tolerance and Quality of Life].

AIM: to assess effect of interval hypoxic-hyperoxic training (IT) on exercise tolerance and quality of life of patients with ischemic heart disease (IHD) receiving optimal medical therapy, as well as the safety of IHHT use. METHODS: Patients with stable IHD with functional class II and III angina (n=46) were randomized into two groups: IHHT (n=27, 15 treatments in 3 weeks), and IHHT imitation (n=19). Cardiopulmonary stress test was performed to evaluate the following parameters of exercise tolerance: peak oxygen consumption (VO2peak, VO2peak/kg), % of predicted peak oxygen consumption (%VO2 peak) and anaerobic threshold (VO2AT). MOS SF-36, SAQ, HADS questionnaires were used for assessment of quality of life (QL). RESULTS: Exercise tolerance (VO2peak/kg) after course of IHHT significantly increased (p=0.03) and remained significantly elevated during subsequent month (p=0.036). Marked improvement was also observed in patients subjective perception of QL. This was evidenced by dynamics of characteristics of physical functioning as well as of psychological state, significant increase of values on all scales of disease-specific questionnaire SAQ, reduction of depression and anxiety according to dynamics of HADS scores. These effects persisted in 1 month after IHHT. IHHT was safe and well tolerated. Side effects were minimal (transient slight dizziness, feeling of shortage of air) and did not require IHHT termination. CONCLUSION: We received clinical confirmation of safety and effectiveness in of IHHT in medically treated patients with stable angina. IHHT was associated with significant improvement of exercise tolerance, subjective perception of QL, reduction of number of angina attacks. Thus, IHHT has significant potential as component of complex treatment and rehabilitation of patients with stable angina.

Spatial Organization of Alpha Range Potentials on EEG and Logical Thinking Effectiveness.

We studied spatial organization of EEG alpha range potentials in volunteers with different results of tasks requiring logical thinking. The examinees with higher cognitive test performance have more labile coherent associations of EEG alpha range potentials, which manifested in changes in the level and structure of these associations at different stages of the test. In individuals with poor results, the number of significant coherent associations and their structure do not change during the problem solving process.

[Dynamics of EEG Alpha-Activity and Heart Rate Variability in Subjects Performing Cognitive Tests].

Changes in the power and coherence of α-activity and heart rate variability (HRV) were studied in students with different performance levels in logical tasks. In those students who reached high scores in the cognitive tests, we observed higher lability of α-activity and HRV; the values and their ratios varied among the stages of intellectual activity. In these subjects, a decrease in the spectral power of α-band was more pronounced than in other groups. We also observed changes in the interhemispheric coherence and in the structure of coherent interactions in the α-range at different stages of task performance. In contrast, the number and structure of coherent interactions in individuals who showed lower results did not significantly vary at different stages of task performance. As compared with this group, the students with higher test results showed a more pronounced decrease in the total spectral power (TP) and an increase in the low frequency/high frequency (LF/HF) ratio which returned to the initial level after the end of the tests. In students with better results in these cognitive tests, the dynamics of RRNN, TP, HF, and LF/H F during task performance correlated with the dynamics of interhemispherical α-band coherence.

[Monitoring of human physiological functions during the daily night sleep].

The basic somnological methodology, which is extensively used in the present time, focuses only on clinical practice. However, this approach is not appropriate for monitoring of physiological functions during natural sleep under home conditions. Our work was designed to develop a new information-and-equipment device for the reliable study of human physiological functions during sleep in the real everyday life. The information complex is a new portable microprocessor device and original software, which is constructed on the basis of PC and provides a control of vital physiological functions during sleep in the real everyday life. We developed a new methodology for the objective comprehensive study of sleep under real day-to-day conditions. This approach allows us to identify the phase structure of sleep and to control cardiovascular functions and breathing on the basis of a cross-correlation analysis of the heart rate and respiratory rate (that reflects the degree of emotional strain). The information system for control of sleep under living conditions is composed from interrelated units, which perform the following functions: registration, identification, and analysis of the phase structure of sleep; wake-up of a subject in a certain time during the pre-determined optimal phase of sleep (as regards the psychophysiological state of this subject); and interruption of a long-lasting hazardous phase of sleep. Due to a complex analysis of physiological functions, the information system provides monitoring of sleep under real living conditions and interruption of hazardous phases of sleep that can be accompanied by serious cardiovascular disorders (i.e., leading to cerebral stroke, myocardial infarction, and sudden death).

Dynamics of heart rhythm characteristics and efficiency of intellectual activity during computer work.

Heart rhythm variability characteristics were studied in volunteers with different stability of the results upon switching from one type of intellectual activity to another. Individuals with stable results differed from those with worse accuracy of information reproduction by high initial CV, total power of heart rhythm variability and power of VLF, LF, and HF spectra. Volunteers with stable results were characterized by high lability manifesting by changing values and proportions of heart rhythm variability characteristics at different stages of activity and by the absence of a relationship between these parameters at different stages of activity and initial status of the volunteer. VLF spectrum power decreased with impairing the accuracy of information reproduction.

Cytokine levels in rat blood and brain structures after administration of lipopolysaccharide.

We compared cytokine profile of rat serum and brain structures after immune status modulation by LPS (30 µg/kg intraperitoneally). The content of inflammatory (IL-1α, IL-1ß, IL-2, IL-6, IFN-γ, and TNF-α) and anti-inflammatory (IL-4 and IL-10) cytokines in biological samples of animals was measured on days 1 and 7 after antigenic stimulation. LPS administration reduced the levels of both inflammatory and anti-inflammatory cytokines in the peripheral blood of the rats, especially on the 1st day. LPS administration was also accompanied by specific changes in cytokine content in the dorsal hippocampus and anterior cingulate cortex. Antigenic stimulation increased the level of anti-inflammatory cytokines IL-4 and IL-10 in the examined brain tissues, the changes were most pronounced on day 1 after LPS injection. No significant changes in the levels of proinflammatory cytokines in the brain tissue of animals were found at the above terms after LPS injection. Thus, peripheral LPS administration to rats shifts the balance between the inflammatory and anti-inflammatory cytokines in the CNS structures towards the latter.

[The autonomic correlates of individual differences in the time parameters and effectiveness of intellectual activity of the person].

The individual differences of autonomic support of intellectual activity (simple and complex sensorimotor reaction, storing and reproduction to the screen of the monitor of the visual information) were studied. Intellectual computer tests passing speed is a relatively steady individual characteristic, revealed in different kinds of activity. Students who reached high speed and accuracy in performance of intellectual visually-motor tasks were characterized high lability of autonomic indices, which manifests itself in a change in the absolute values and relationship of the characteristics of heart and respiration rate in accordance with activity stages. These changes were specific for each form of activity and were connected with the results of the tests. In an initial condition these students differed high values of TP and power of LF and HF ranges of heart rate variability at a LF/HF ratio close to unity.

[Microcirculatory reactivity features in almost healthy people during acute moderate hypoxia and hyperoxia modeling].

The dynamics of the microvascular circulation and tissue oxygenation in the hypoxic test and subsequent hyperoxia are considered. In 30 healthy young men indicators of microcirculation and tissue oxygenation (laser Doppler flowmetry, and the optical tissue oximetry) during the hypoxic test - HT (10 min breathing by gas mixture with 10% O2 followed by hyperoxia (30% O2) were registered. It is found that the HT does not entail changes in the relative level of tissue oxygen saturation (SO2), but leads to a relative degree of tissue oxygen extraction significant reduction (δSaO2-SO2) with a rapid recovery in the hyperoxic phase. This is accompanied by activation of neurogenic sympathetic-related vasomotor mechanisms, as well as the endothelium-dependent microvascular tone component with a reduction in blood shunting (BSh) mostly in the hyperoxic phase and not during hypoxia. The nature of the microcirculatory response to hypoxia depends on the initial individual resistance--sensitivity level to hypoxia. Among the subjects sensitive to hypoxia HT led to a significant reduction in SaO2 and δSaO2-SO2 in the absence of changes in the microcirculation regulation. Among the subjects resistant to hypoxia HT leads to the nutritive blood flow activation by increasing the initially decreased endothelium-dependent and neurogenic sympathetic components in regulation of microhaemodynamics activity, reduction of blood shunting. At the same time δSaO2-SO2 has not significantly changed, and the activation of micro blood circulation remains in the hyperoxic recovery stage. Identified functional criteria for contribution of endothelial and neurogenic vasomotor component in the regulation of microhemodynamics in HT substantiate the contribution of the microcirculatory part and confirm the important role of hyperoxic phase in the body' hypoxia-hyperoxia adaptive response.

[The microcirculatory blood flow and autonomic regulation's functional state in young people with different levels of subjectively experienced psychological stress].

A comprehensive comparative analysis of hemodynamics, microcirculation (the method of laser Doppler flowmetry with occlusal probe and the optical tissue oxymetry), blood circulation neuro-humoral regulation (analysis of heart rate variability - HRV) between almost healthy young people with different levels of subjectively experienced emotional stress is given. Depending on the degree of everyday stress (acute and/or chronic) the character of neuro-autonomic regulation of blood circulation, as well as the state of the microcirculatory blood flow and its regulation are substantially different. Moderate stress is accompanied sympathetic-parasympathetic regulatory mechanisms co-activation with augmented HRV baroreflex regulation circuits that compensate hemodynamic changes and is not accompanied by hypertensive reactions. An increase in the activity of neurogenic and myogenic tone microhemodynamics in the examinees with moderate stress is discovered, which determines a high probability of blood shunting in tested tissue and decrease of relative oxygen extraction. Moderate levels of stress are also associated with increase in a latency of post-occlusive vasoreactive hyperemia, which is considered to be an initial sign of the endothelium-mediated dysfunction of microcirculation.

[Adaptation to hypoxia and hyperoxia improves physical endurance: the role of reactive oxygen species and redox-signaling].

We have conducted theoretical foundation, experimental analysis and a pilot study of a new method of adaptation to hypoxia and hyperoxia in the prevention of hypoxic and stress-induced disorders and improving the body's tolerance to physical stress. It has been shown in the experimental part that a combination of physical exercise with adaptation to hypoxia-hyperoxia significantly increased tolerance to acute physical load (APL) and its active phase. Analysis of lipid peroxidation processes, antioxidant enzymes and HSPs showed that short-term training for physical exercise by itself compensates the stressor, but not the hypoxic component of the APL, the combination of training with adaptation to hypoxia-hyperoxia completely normalizes the stressor and hypoxic components of APL. The pilot study has been performed to evaluate the effectiveness of hypoxic-hyperoxic training course in qualified young athletes with over-training syndrome. After completing the course of hypoxia-hyperoxia adaptation, 14 sessions, accompanied by light mode sports training, the athletes set the normalization of autonomic balance, increased resistance to acute hypoxia in hypoxic test, increased physical performance--increased PWC170, maximal oxygen consumption (VO2max) parameters, their relative values to body mass, diminished shift of rate pressure product in the load. Thus, we confirmed experimental findings that hypoxic-hyperoxic training optimizes hypoxic (increased athletes resistance to proper hypoxia) and stress (myocardium economy in acute physical stress testing) components in systemic adaptation and restoration of athletes' with over-training syndrome.

The effect of a Radiology Conference consultation on cancer patients management.

BACKGROUND: The quantitative effect of consultation on cancer patient's management at a Radiology Conference was studied. PATIENTS AND METHODS: This prospective study included consecutive patients presented at the Radiology Conference of the Division of Oncology. Following the case presentation and discussion, the patient's oncologist completed a questionnaire which asked whether the consultation at the conference added new information regarding the patient's disease status, whether it influenced patient management and, if so, to what extent. RESULTS: Three hundred and eighty-three patients were included in the study. Significant new information was added for 189 (49%) patients and less consequential information was added for 134 (35%) patients. Major changes in management occurred in 143 (37%) patients after the Radiology Conference and minor changes were made in 56 (15%) patients. The influence of the cancer type on the rate of significant change in treatment and on the rate of major information addition was not statistically significant. CONCLUSION: Consultation at a Radiological Conference in a tertiary center led to major changes in the management of 37% of the cancer patients presented and provided important information regarding the patient's disease in up to 50% of patients.

[Interval hypoxic-hyperoxic training in the treatment of the metabolic syndrome].

AIM: to investigate the possibility of a new method--interval hypo-hyperoxic training (IHHT)--in the correction of the individual components of metabolic syndrome. MATERIALS AND METHODS: The study included 35 patients with metabolic syndrome (alimentary obesity 1-3rd stage [BMI over 30 kg/m2], violation of carbohydrate tolerance or diabetes mellitus type II, hypertension and dyslipidemia). All patients were random separated into three groups: control (11 pers., basic therapy), trial 1 (13 pers. who have undergone 12 procedures of the IHHT) and trial 2 (11 pers. who have undergone IHHT in parallel with systemic hyperthermia and vibrating massage hardware). Course duration was 21 days average. Prior to the course procedures IHHT and the 3-day 4 upon completion all patients were fully examined. This examination included history taking, assessment of diet, psychometric testing, counseling psychologist to determine the type of feeding behavior, anthropometric measurements; body impendansemetria, biochemical study of blood determining the level of total cholesterol, HDL, LDL, TG, fasting plasma glucose (GP), 6-minute walk test to assess physical performance. Was established that the use of hypo-hyperoxic exercise (alone or in combination with systemic hyperthermia and hardware vibratory) leads to a significant reduction in body weight. It mainly arise by reducing fat mass accompanied by a reduction of total cholesterol, LDL, GPN, optimization of blood pressure, increased hypoxic stability, physical endurance, improved mental status. At individual selection of the course structure, dosing of hypoxic effects, combined with other physiotherapy method has some promise in treatment and rehabilitation of patients with metabolic syndrome.

[Assessment of cardiorespiratory functions in patients receiving suggestive psychotherapy].

It is shown that suggestive psychotherapy based on verbal suggestions provides a tool for individual correction of the patient's functional state. It reduces sympathetic and promotes parasympathetic influences, decreases high initial level of psychoemotional tension, and normalizes relationship between cardiac and respiratory rhythms. Also, suggestive psychotherapy has beneficial effect on the psychological sphere and subjective feeling of well-being, reduces anxiety, strengthens the sense of confidence and hope for a cure.