Synergies of THESEUS with the large facilities of the 2030s and guest observer opportunities.

The proposed THESEUS mission will vastly expand the capabilities to monitor the high-energy sky. It will specifically exploit large samples of gamma-ray bursts to probe the early universe back to the first generation of stars, and to advance multi-messenger astrophysics by detecting and localizing the counterparts of gravitational waves and cosmic neutrino sources. The combination and coordination of these activities with multi-wavelength, multi-messenger facilities expected to be operating in the 2030s will open new avenues of exploration in many areas of astrophysics, cosmology and fundamental physics, thus adding considerable strength to the overall scientific impact of THESEUS and these facilities. We discuss here a number of these powerful synergies and guest observer opportunities.

[THE EFFECT OF MOTION SICKNESS ON THE SLEEP-WAKE CYCLE IN RATS EXPOSED TO PRENATAL HYPOXIA].

This study is a continuation of our research of phenomenology and mechanisms of motion sickness (MS) and the relation of this phenomenon to features of sleep-wake cycle (SWC) changes. It presents data about the effect of MS on SWC in 30-day-old intact rats and rats exposed previously to prenatal hypoxia on days 13 and 19 of gestation. In all groups of animals MS was shown to reduce significantly the waking time and to increase the time of paradoxical sleep (PS). For the first time it became possible to reveal a connection between hypothalamic mechanisms controlling MS and SWC and to suggest the role of this connection in mechanisms of development of the sopite syndrome which may be the only manifestation of MS in some animals and man. The results obtained demonstrate that hypoxia on day 19 of gestation has a greater damaging effect on the thalamocortical sleep-regulating structures than hypoxia on day 13 when only hypothalamic-hippocampal systems controlling slow-wave sleep were found disturbed. Against this background MS substantially suppresses the activity of the brain excitatory systems which provide wake- fulness maintenance (it appears to be the ascending reticular activating system) and enhances the work of those activating systems that control PS. It is in rats exposed to preliminary hypoxia on day 19 of gesta- tion, where it was possible to show the role of the evolutionary young thalamocortical system in the control of PS.

[BRADY-ARRHYTHMIAS IN THE OBSTRUCTIVE SLEEP APNEA SYNDROME: DANGEROUS COMPLICATION OR DEFENSE MECHANISM?].

Sleep is characterized by cycling and consecutive alternation of different phases and stages, each of them featuring intrinsic changes of vegetative regulation with oscillations of heartbeat rate that may cause development of cardiac rhythm disorders especially under presence of concomitant somatic diseases. This paper deals with the problems of interrelationships between disturbances of heart conduction and obstruc- tive sleep apnea. It is shown that some mechanisms of the occurrence of brady-arrhythmias (first of all, features of vegetative regulation with increasing parasympathetic tone) under sleep arrests are inherent to human divers as well as to mammals conducting water or near-water way of living associated with forced breathing delays at diving and prolonged staying under water. These mechanisms may carry out defense function.

[ON THE INFLUENCE OF PRENATAL HYPOXIA ON FORMATION OF THE OREXINERGIC SYSTEM AND SLEEP-WAKEFULNESS CYCLE IN EARLY POSTNATAL ONTOGENESIS OF RATS].

The role of orexin in the organization of sleep-wakefulness cycle (SWC) is well known. The aim of this study was to examine the terms of formation of the orexinergic system in the rat postnatal ontogenesis and to assess the role of orexin A in SWC organization under normal conditions and after prenatal hypoxia realized on days 14 and 19 of the embryogenesis. SWC was investigated in 30-day-old rats with elect- rodes implanted into the somatosensory and occipital cortex. Immunoreactivity in the orexinergic structures of the lateral hypothalamus was also studied. It was shown that in the control 14-day-old animals the orexinergic structures were at the formation stage whereas in the 30-day-old ones they were already formed as in adults. In the 14-day-old rats prenatal hypoxia evoked retardation of the orexinergic system for- mation terms. In the 30-day-old rats the orexinergic system activity after hypoxia was increased, with hypoxia on day 19 activating this system stronger than hypoxia on day 14 of gestation. These changes were reflected in the SWC formation in the 30-day-old rats as shortening of the slow-wave phase of sleep, increase in the fitful sleep and in the number of transitions from the slow-wave to the fast-wave phase of sleep. The results obtained are discussed in the light of the adaptation-compensatory role of the orexinergic system in the postnatal ontogenesis after prenatal damage affecting the central neural system.

[EFFECTS OF ELECTRICAL STIMULATION OF NUCLEUS RETICULARIS PONTIS ORALIS ON THE SLEEP-WAKING STATES IN KRUSHINSKII-MOLODKINA STRAIN RATS].

The effects of electrical stimulation of nucleus reticularis pontis oralis on the behavior and brain electrical activity during all phases of the sleep-waking cycle was studied in Krushinskii-Molodkina strain rats, which have an inherited predisposition to audiogenic seizures. Electrical stimulation with 7 Hz frequency in the deep stage of slow-wave sleep cause appearance the fast-wave sleep. Similar stimulation during fast-wave sleep periods did not effects on the electrographic patterns and EEG spectral characteristics of hippocampus, visual, auditory and somatocnen nrnrenc nf the cnrtey ThPe sfimul1stinns did nnt break a fast-wave sleenhut increased almost twice due the duration of these sleep episodes. After electrical stimulation by same frequency during the wakeftlness and superficial slow-wave sleep states, the patterns and spectral characteristics of brain electrical activity in rats showed no significant changes as compared with controls. The results of this study indicate that the state of the animals sleep-waking cycle at the time of stimulation is a critical variable that influences the responses which are induced by electrical stimulation of the nucleus reticularis pontis oralis.

[Treatment of myofascial pain syndrome].

OBJECTIVE: To study different methods of treatment of patients with myofascial pain syndrome (MFPS). MATERIAL AND METHODS: We evaluated the efficacy of complex treatment in 152 patients with chronic tension-type headache (СЕЕР) and 96 patients with facial MFPS. The treatment included standard methods (reflex therapy of СЕЕР and local injections of a combination of local anesthetics with small doses of steroids in trigger points in patients with facial MFPS. To assess the efficacy of tizanidine, patients were randomized into two comparable groups. The duration of the study was 12 weeks. RESULTS AND CONCLUSION: The combined therapy, including reflex action and tizanidine, speeds recovery from pain and ensures the stability of results.

Positron annihilation on defects in silicon irradiated with 15 MeV protons.

Microstructure and thermal stability of the radiation defects in n-FZ-Si ([P] ≈ 7 × 10(15) cm(-3)) single crystals have been investigated. The radiation defects have been induced by irradiation with 15 MeV protons and studied by means of both the positron lifetime spectroscopy and low-temperature measurements of the Hall effect. At each step of the isochronal annealing over the temperature range ∼60-700 °C the positron lifetime has been measured for the temperature interval ∼30-300 K, and for samples-satellites the temperature dependences of the charge carriers and mobility have been determined over the range ∼4.2-300 K. It is argued that as-grown impurity centers influence the average positron lifetime by forming shallow (E(b) ≈ 0.013 eV) positron states. The radiation-induced defects were also found to trap positrons into weakly bound (E(b) ≤ 0.01 eV) states. These positron states are observed at cryogenic temperatures during the isochronal annealing up to T(anneal.) = 340 °C. The stages of annealing in the temperature intervals ∼60-180 °C and ∼180-260 °C reflect the disappearance of E-centers and divacancies, respectively. Besides these defects the positrons were found to be localized at deep donor centers hidden in the process of annealing up to the temperature T(anneal.) ≈ 300 °C. The annealing of the deep donors occurs over the temperature range ∼300-650 °C. At these centers positrons are estimated to be bound with energies E(b) ≈ 0.096 and 0.021 eV within the temperature intervals ∼200-270 K and ∼166-66 K, respectively. The positron trapping coefficient from these defects increases from ∼1.1 × 10(16) to ∼6.5 × 10(17) s(-1) over the temperature range ∼266-66 K, thus substantiating a cascade phonon-assisted positron trapping mechanism whose efficiency is described by ≈T(-3) law. It is argued that the value of activation energy of the isochronal annealing E(a) ≈ 0.74-0.59 eV is due to dissociation of the positron traps, which is accompanied by restoration of the electrical activity of the phosphorus atoms. The data suggest that the deep donors involve a phosphorus atom and at least two vacancies. Their energy levels are at least at E > E(c) - 0.24 eV in the investigated material.

Effects of memantine on convulsive reactions and the organization of sleep in krushinskii-molodkina rats with an inherited predisposition to audiogenic convulsions.

Krushinskii-Molodkina rats, which have a genetic predisposition to audiogenic convulsions, are used as a natural animal model for studies of the actions of anticonvulsants. It is important to understand the extent to which changes in glutamatergic synaptic transmission is involved in the mechanisms producing convulsive states and in the functional organization of the sleep-waking cycle in rats of this strain. The present report describes experiments addressing this, in which i.m. doses of 5 and 10 mg/kg of a noncompetitive NMDA glutamate receptor antagonist of the memantine type were given at different times (30 min, 1, 2, and 3 h) before presentation of sound stimuli (sine-wave tones at 8 kHz, 90 dB). Effects on the latent periods of the initial motor excitation, the appearance of clonic convulsions of different intensities, and, finally, tonic convulsions with limb and tail extension were evaluated. The greatest attenuation of convulsive seizures, to a level consisting only of motor excitation, was obtained in 60% of the rats between 1 and 2 h after administration. There were no differences between the effects of doses of 5 and 10 mg/kg. When doses were given 3 h before sound provocation, convulsive reactions became more marked than at 2 h, though they were nevertheless more marked than in controls. Krushinskii-Molodkina rats with chronically implanted electrodes for recording brain electrical activity were used to study the effects of memantine on the organization of sleep. These experiments showed that the rats' sleep during the first hour after dosage consisted only of short episodes of superficial slow-wave sleep, and that even this sleep disappeared completely 54.4 +/- 4.9 and 39.9 +/- 5.2 min after administration of the agent at doses of 5 and 7 mg/kg, respectively. Rats showed a complete absence of sleep for 2 and 2.5 h, respectively, after which episodes of slow-wave sleep reappeared. The first episodes of REM sleep was seen in rats only after 3.3 +/- 0.2 and 3.7 +/- 0.2 h after memantine injections. The appearance of these episodes provided evidence that the effects of memantine on the activity of the somnogenic system of the animals' brains were complete and that recovery of the normal organization of the sleep-waking cycle had started. The synchronicity and codirectionality of the blocking action of memantine on sleep organization and measures of audiogenic convulsions in Krushinskii-Molodkina rats is evidence for the involvement of glutamatergic synapses with NMDA receptors in both the regulation of the somnogenic systems and the pathogenesis of epileptiform manifestations in rats.

The dopaminergic system of the telencephalo-diencephalic areas of the vertebrate brain in the organization of the sleep-waking cycle.

The aim of the present work was to study the involvement of the dopaminergic system of the telencephalic and diencephalic areas of the vertebrate brain in the organization of the sleep-waking cycle in cold-blooded and warm-blooded vertebrates. Immunohistochemical studies of tyrosine hydroxylase content, this being the key enzyme in dopamine synthesis, in the striatum, supraoptic and arcuate nuclei, and zona incerta of the hypothalamus of sturgeon and mammals (rats) of three age groups (14 and 30 days and adults), in conditions of tactile and sleep-deprivation stressors. In fish, transient stress was followed by the detection of tyrosine hydroxylase-immunoreactive cells in all parts of the brain. In prolonged stress, tyrosine hydroxylase-immunoreactive cells and fibers were not found in the forebrain, though they were well represented in the hypothalamic nuclei. In 14-day-old rat pups, 2-h sleep deprivation increased the tyrosine hydroxylase content of fibers in the caudate nucleus and cells in the zona incerta of the hypothalamus, while 30-day-old animals subjected to 6-h sleep deprivation showed increases in tyrosine hydroxylaseimmunoreactive material contents in cells in the paraventricular nucleus and decreases in the quantity in fibers. In adult rats, the arcuate nucleus and zona incerta showed decreases in the content of tyrosine hydroxylase-immunoreactive material on the background of sleep deprivation, with increases during postdeprivation sleep. These data are discussed in the light of the phylo- and ontogenetic development of the neurosecretory and neurotransmitter functions of the dopaminergic system in the evolutionarily ancient diencephalic and evolutionarily young telencephalic areas of the vertebrate brain as major systems triggering and maintaining the functional states of the body during the sleep-waking cycle.

The dopaminergic nigrostriatal system in sleep deprivation in cats.

The dynamics of changes in electrophysiological measures of the sleep-waking cycle were analyzed in Wistar rats after 6 h of sleep deprivation by gentle waking and subsequent 9-h post-deprivation sleep. A delayed sleep "overshoot" reaction was observed 2.5-3 h after sleep deprivation, as a moderate increase in the proportions of slow-wave and fast-wave sleep in the sleep-waking cycle. Immunohistochemical studies were performed in relation to changes in the sleep-waking cycle, with the aim of identifying changes in the quantities of immunoreactive dopamine D1 and D2 receptor material and tyrosine hydroxylase, the key enzyme in dopamine synthesis in the nigrostriatal system. In conditions of sleep deprivation, the caudate nucleus showed increases in the quantities of dopamine D1 and D2 receptor material, while there was a simultaneous decrease in the amount of immunoreactive material in the substantia nigra. Post-deprivation sleep was accompanied by decreases in the quantities of immunoreactive D1 receptor material and increases in D2 receptor material in the caudate nucleus, with an increase in the quantity of immunoreactive tyrosine hydroxylase in the substantia nigra. These data provide evidence of the active role of the dopaminergic nigrostriatal system which, along with other CNS transmitter systems, supports telencephalic-diencephalic interactions, in the sleep-waking cycle.

Activity of the hypothalamic-pituitary-adrenocortical system and sleep-wake cycle in rats with acute systemic inflammation.

Activity of the hypothalamic-pituitary-adrenocortical system and EEG characteristics of the sleep-wake cycle were studied on adult male Wistar rats with acute inflammation produced by bacterial lipopolysaccharide in a dose of 250 microg/100 g body weight. Blood concentrations of adrenocorticotropic hormone and corticosterone increased by 6 and 10 times, respectively, 30 min after lipopolysaccharide administration and peaked 2 hours after challenge. In this period the sleep-wake cycle underwent the most pronounced changes that could be attributed to the stupor-like state observed in clinical practice. It was manifested in dissociation between locomotor activity of animals and EEG characteristics, suppression of EEG components in slow-wave sleep, increase in the number of beta-waves, and decrease in the number of delta-waves in EEG. In the present work we consider possible mechanisms of temporal relationships between activity of the hypothalamic-pituitary-adrenocortical system and disorganization of the sleep-wake cycle during acute systemic inflammation.

Effect of generalized seizures on the structure of the sleep-waking cycle and the EEG in rats with an inherited predisposition to audiogenic convulsions.

Data are presented on the effects of generalized tonic-clonic seizures on the structure of the one-day sleep-waking cycle in Krushinskii-Molodkina (KM) rats, which have a genetic predisposition to audiogenic convulsions. Spectral and correlation analysis of EEG activity in the hippocampus, caudate nucleus, medial central nucleus of the thalamus, and in the somatosensory, visual, and auditory regions of the cortex of these animals was carried out for time intervals before and after convulsions. After seizures, rats showed a prolonged (up to 3.5 h) reduction in fast-wave sleep (FWS) with no subsequent compensatory increase in this phase in the sleep-waking cycle, while a disturbance in slow-wave sleep (SWS) was minor and short-lived (not more than 2 h). It is suggested that generalized paroxysmal attacks predominantly involve disorganization of the function of the systems regulating FWS, while the synchronizing mechanisms of the brain, responsible for SWS, are affected to a lesser extent.

Comparative investigation of anticlastogenic effects in cell cultures of healthy donors and patients with nettle-rash.

In cultures of lymphocytes from 12 healthy donors and 12 patients with nettle-rash (NR) the anticlastogenic effect of the antimutagens WR-2721 (WR), bemitil (BM), tomerzol (TM) and interferon (IF) on the induction of chromosomal aberrations by photrin (PT) and dioxidine (DX) was investigated. There were no statistically significant differences between healthy donors and patients with NR in the levels of chromosomal aberrations that were spontaneous or induced by PT or DX. Statistically significant protective effects of BM, WR, TM and IF were demonstrated in cells of healthy donors after treatment with PT or DX, and after modification of the clastogenic action of PT in lymphocytes of NR patients. There was no protective effect of any of the anticlastogens after treatment of the lymphocyte cultures from NR patients with DX. That observation allows us to suggest the test of anticlastogenic action as a measure of sensitivity of the chromosomal apparatus in groups with different genetic risks.

Cortico-striatal relations under conditions of interaction of monomodal afferent volleys.

Evoked potentials in response to a combination of electrostimulation of both anterior extremities were investigated under conditions of a chronic experiment on monkeys in the head of the caudate nucleus and frontal and somatosensory cortex. Three types of interaction of afferent volleys evoked by spontaneous stimulation were noted: facilitation, summation, and depression. A high degree of correlation of the responses in the head of the caudate nucleus with the responses in the frontal cortex was noted. The role of the frontal and somatosensory cortex in the formation of sensory responses in the caudate nucleus is compared.