The exact location of the dominant pacemaker site in adult bird heart continues to be ill-defined. The aim of this study was to identify the localization of the dominant pacemaker and to investigate its electrophysiological characteristics in isolated sinoatrial preparations of the adult chicken (Gallus gallus domesticus) heart. The dominant pacemaker was localized at the base of the right leaflet of the valve of the right cranial vena cava and at the base of both leaflets of the valve of the caudal vena cava. But latent pacemakers were also identified in regions around these valves. Additionally, the valve leaflets generated conducting-like APs that with high amplitude, fast maximal upstroke velocity (greater than in working myocardium) and with diastolic depolarization. The avian sinoatrial junction is electrophysiologically heterogeneous. The avian dominant pacemaker site is more extensive than that in mammals. These findings establish a foundation for understanding species-specific pacemaker mechanisms and their evolution.

BACKGROUND:Maturation of the mouse is accompanied by the increase in heart rate. However, the mechanisms underlying this process remain unclear. We performed an action potentials (APs) recordings in mouse sinoatrial node (SAN) true pacemaker cells and in silico analysis to clarify the mechanisms underlying pre-postnatal period heart rate changes. RESULTS:The APs of true pacemaker cells at different stages had similar configurations and dV/dtmax values. The cycle length, action potential duration (APD90), maximal diastolic potential (MDP), and AP amplitude decreased, meanwhile the velocity of diastolic depolarization (DDR) increased from E12.5 stage to adult. Using a pharmacological approach we found that in SAN true pacemaker cells ivabradine reduces the DDR and the cycle length significantly stronger in E12.5 than in newborn and adult mice, whereas the effects of Ni2+ and nifedipine were significantly stronger in adult mice. Computer simulations further suggested that the density of the hyperpolarization-activated pacemaker сurrent (If) decreased during development, whereas transmembrane and intracellular Ca2+ flows increased. CONCLUSIONS:The ontogenetic decrease in IK1 density from E12.5 to adult leads to depolarization of MDP to the voltage range in which calcium currents are activated, thereby shifting the balance from the "membrane-clock" to the "calcium-clock."

The number of physiological groups, biodiversity, enzymatic activity and some physiological and biochemical properties of microorganisms isolated from thermal waters and microbial mats of Kamchatka were studied. A low content of microorganisms with a predominance of denitrifying (Verhne-Vilyuchinsky) and nitrifying bacteria (Sredne-Paratunsky springs) was shown. Gram-positive spore- forming rods of the genus Bacillus predominated among the isolated bacteria. The isolated microorganisms had extracellular enzymatic activity and were capable of growing in wide ranges of temperatures, pH and NaCl concentration. Strains of thermophilic bacteria are of interest for biotechnology purposes.

Migraine is a chronic neurological disorder that is associated with considerable disadaptive effect on patients. Despite the development of pharmacotherapy strategies for migraine, only one third of patients are satisfied with their overall treatment. Many migraine patients turn to complementary and alternative medicine (CAM), which is not usually considered a part of conventional medicine and is not always evidence-based. In practise, however, they are often used to improve the effectiveness of standard therapy or to provide alternative treatment. In addition, in CAM methods, the patient is actively involved in the choice of treatment strategies, and they have good adherence. The basic principles and approaches of CAM are increasingly being introduced into clinical practise. This review discusses the principles of CAM in the treatment of migraine as a holistic approach using lifestyle strategies and selected non-pharmacological treatments that have been shown to be effective and rational.

This review summarises the data available in the literature. It also includes the authors' published results of precision densimetric measurements. The research concerns with the physically unusual phenomenon of "thermally activated isobaric partial densification of the structure" (TIPCS) of dissolved water, or its so-called "negative partial molar expandability" (NPEA) in several organic solvents. They contain amphiproton hydroxyl-containing media of three alcohols: methyl alcohol (MA), tertiary butyl alcohol (TBAlcohol), and amyl or pentyl alcohol (TPA), so asprotophilic media of two amines: tert butylamine (TBAmine) and ethylenediamine (EDA). The discussed TIPCS phenomenon, associated with a decrease in the standard (partial at infinite dilution) volume of solvated water with increasing temperature, was discovered about half a century ago in alkanol solutions of H2O and recently - in water-containing media of alkylamines. However, nowadays this extraordinary effect has not yet found its physically based interpretation. It allows ones to predict the possibility of TIPCS occurrence in the binary liquid-phase system specifically selected for the study. Our comprehensive data analysis allowed us to make several inferences regarding the main characteristics of a standard solution of H2O in an organic solvent. They cause extraordinary changes in the volume of the formed solvatocomplex of water under the influence of increasing temperature. Firstly, the energy parameters of the intermolecular interaction (relative affinity) water solvent noticeably dominate over those of the solvent-solvent interaction. Those differences become more evident with increasing temperature. Secondly, a higher rate of thermal expansion of the organic solvent structure in volume (inbulk) is found than influence of temperature on structural packing of the resulting mixed molecular aggregate or water solvates complex. Thirdly, the difference in the parameters of water-solvent and solvent-solvent interactions depends not only on the proton-donor/acceptor properties of the molecules contacting in solution, but also on the configuration of the structural packing of the solvating medium. It determines the nature of steric hindrances to the formation of H-bonds. Therefore, the absolute values of the mentioned parameters of relative affinity at 298.15 K increase in the series: MA << EDA ≈ TBAmine < TPAlcohol < TBAmine. It can indicate a relative strengthening of the specific interaction (mainly through the formation of hydrogen bonds) between the molecules of water and amphiprotonic or protophilic solvent in the above sequence. Indeed, difference in the solvent-solvent and water-solvent hydrogen bonding energies in the discussed liquid media of alkylamines (TBAmine and EDA) and tertiary isomeric alkanols (TBAlcohol and TPA) - with the most evident basicity - turned out to be noticeably larger than in the structural packing of water methanol solution. The ability of the components to specific interactions is quite comparable in those compounds.

Aim. To assess the features of the clinical picture of coronary artery disease (CAD) and the prognosis of patients with myocardial infarction with depressive disorder (DD). Materials and methods. We examined 101 patients with stable CAD who had myocardial infarction more than six months ago: 67 CAD patients with depression (Group 1) and 34 CAD patients without depression (Group 2). The clinical picture of CAD was assessed by complaints, angina self-monitoring diaries, and exercise tests. The presence and severity of DD was determined using psychometric scales: BDI (Beck Depression Scale), HADS (Hospital Anxiety and Depression Scale) and the opinion of a psychiatrist. Five-year survival information was obtained through telephone interviews with patients and their relatives. Results. In patients with CAD and DD in comparison with patients without DD self-monitoring diaries revealed more frequent angina attacks: 9 [6; 12] vs 6 [4; 7] per week (p=0.0001), the greater need for sublingual nitrates: 2 [0; 9] pills vs 0 [0; 4] pills (p=0.0001). DD significantly reduced exercise tolerance: 370 [250; 450] meters vs 435 [350; 500] meters using the six-minute walk test (p=0.04), according to the results of bicycle ergometry – 50 [25; 75] W vs 75 [50; 75] W (p=0.03). After 5 years of follow-up patients with comorbidities (CAD and DD) had a greater number of deaths: 13 (19.4%) vs 2 (5.9%), respectively, survived – 54 (80.6%) vs 32 (94.1%) (Gehan–Wilcoxon test, p=0.04). Conclusion. The comorbidity CAD and DD leads to a worsening of the clinical course of CAD and prognosis, which actualizes the need for verification of the diagnosis of DD and timely prescription of antidepressant therapy.

Objective: to conduct a comparative analysis of factors associated with the development of medication overuse headache (MOH), considering demographic characteristics of patients and comorbid pathology.Material and methods. A prospective study was conducted at "Europe–Asia" International Medical Center. The main group comprised patients with primary headache (HA) aged 18 years and older with MOH, and the control group comprised patients with primary HA without MOH of comparable gender and age. A semi-structured interview was conducted with the patients and additional examinations were performed, including MRI of the brain if indicated. The study included 171 patients with MOH (mean age 43.3 years, 82% women) and 173 patients without MOH (mean age 41.4 years, 75% women).Results. Chronic migraine occurred more frequently in the MOH group (53 and 16%, respectively; p<0.001; OR 5.9; 95% CI 3.6–9.8). One third of patients in both groups suffered from chronic tension-type headache (CTH). Episodic migraine and episodic CTH occurred more frequently in patients without MOH (p<0.001). Patients in the MOH group were more frequently divorced (11.7 and 2.9%, respectively; p=0.002; OR 4.5; 95% CI 1.6–12.2). The majority of patients (76%) in both groups were employed, had a higher education (65% with MOH and 74% without MOH) and were married (63% with MOH and 72% without MOH).The analysis of more than 20 comorbid diseases revealed that three factors were most frequently associated with the development of MOH: chronic insomnia (60.2 and 47.4% respectively; p=0.02; OR 1.7; 95% CI 1.1–2.6), restless legs syndrome (37.4 and 22% respectively; p=0.002; OR 2.1; 95% CI 1.3–3.4) and subjective cognitive impairment (76 and 53.2% respectively; p<0.001; OR 2.8; 95% CI 1.8–4.8).Conclusion. Sleep disturbance, subjective cognitive impairment and marital status of patients are most frequently associated with MOH, indicating the great importance of these factors in the development of MOH and opening new opportunities for its prevention.

OBJECTIVE:To analyze complaints about sleep disorders and assess the incidence of various sleep disorders, using relevant scales, in patients with medication-overuse headache (MOH) in comparison with patients without MOH. MATERIAL AND METHODS:The prospective case-control study included 171 patients, aged 18 years and older, with MOH (main group), and173 patients with primary headaches without MOH (control group). A neurologist conducted an initial examination and professional interview before the start of treatment. To diagnose sleep disorders, the International Classification of Sleep Disorders (3rd edition, 2014) was used. Additionally, an assessment was made using the Insomnia Severity Index Scale, the Epworth Sleepiness Scale (ESS) and the Lausanne Obstructive Sleep Apnea Syndrome Scale (NoSAS). RESULTS:Statistically significant differences were revealed in the prevalence of the following complaints about sleep disorders in patients with MOH: lack of sleep (51.5%), frequent awakenings during sleep (43.3%), discomfort in legs before falling asleep or at rest in the evening (37.4%). Difficulties falling asleep occurred equally often in both patients with MOH (43.9%) and without MOH (37.0%), as well as daytime sleepiness (40.4% vs 36.4%) and the presence of snoring (13% of patients in each group). Patients with MOH were significantly more likely to suffer from chronic insomnia (60.2% and 47.4%, respectively, p=0.02; OR 1.7; 95% CI 1.1-2.6) and restless legs syndrome (37.4% and 22.0%, respectively, p=0.002; OR 2.1; 95% CI 1.3-3.4). The incidence of hypersomnia and obstructive sleep apnea syndrome did not have statistically significant differences. CONCLUSION:Patients with MOH compared to patients without MOH have a significantly higher incidence of main complaints of sleep disorders, chronic insomnia and restless legs syndrome, which indicates the importance of sleep disorders in the pathogenesis of medication-overuse headaches and requires timely diagnosis and treatment to prevent the progression of both headaches and sleep disorders.

BACKGROUND AND AIM:Explicit diagnostic criteria for transient ischemic attack (TIA) (EDCT) have been recently proposed based on the assumption, that a migraine aura-like symptom is not typical for a TIA. However, migraine-like symptoms have been unexpectedly frequent in patients with confirmed ischemic stroke. This cross-sectional study aimed to field-test the EDCT to distinguish transient neurological symptoms caused by cerebral infarction from those caused by migraine aura. METHODS:The sensitivity, specificity, positive and negative predictive values of the EDCT score were calculated in samples of patients with (i) transient symptoms caused by cerebral infarction confirmed by imaging and (ii) patients with migraine with aura diagnosed according to the International Classification of Headache Disorders 3rd edition. Sensitivity, specificity, positive and negative predictive values of the original and modified EDCT were calculated, as well as area under the curve adjusted for age and sex using the logistic regression method. RESULTS:The study population included 59 patients with cerebral infarction and 324 patients with migraine with aura. The median age of the stroke group was 72 (IQR 61-81) and of the migraine group 39 (IQR 29-53). There were 36 (61%) men in the stroke group and 221 (68%) women in the migraine group. For the detection of TIA with imaging-proven cerebral infarction, the original EDCT had a sensitivity of 90% (95%CI 79-96), a specificity 77% (95%CI 72-82), a positive predictive value of 42% (95%CI 33-51), and the negative predictive value 98% (95% CI 95-99). For the modified EDCT, the sensitivity was 81% (95%CI 69-90), the specificity 97% (95%CI 94-98), the positive predictive value 81% (95%CI 69-90), and the negative predictive value 97% (95%CI 94-98). CONCLUSIONS:The original and modified EDCT criteria miss up to 1 of 10 and 1 of 5 patients, respectively, with transient symptoms due to cerebral infarction. However, the modified EDCT criteria are more specific but less sensitive in detection of ischemic events. The optimal combination of clinical markers to reliably distinguish TIA from migraine aura remains to be found.

OBJECTIVE:To assess the prevalence of various complaints indicating poor sleep quality and its disturbances in men and women with primary headaches.MATERIAL AND METHODS:In total 305 patients (mean age 45 years, age range 18-89 years) with primary headache disorders and complaints of poor quality of sleep were included in the study. Women prevailed among these patients (79%). The average age of men (41.6) and women (45.8) had no statistically significant differences (p=0.8). The initial examination and professional face-to-face interview were initially conducted by an experienced neurologist specializing in the treatment of headaches. Within a week after that, before the start of treatment, patients were interviewed by telephone using standardized questionnaires by specially trained students and physicians.RESULTS:A frequent occurrence of many complaints of sleep disturbances were found in primary headache disorders, both in men and women, they included daytime sleepiness (75.7%), lack of sleep (69.2%), difficulty in falling asleep (57.4%), sleep disruption (51.5%), early morning awakening (47.5%), snoring (18.7%). We found the predominance of these complaints in people over 50 years old. Women had these complaints more frequently than men, besides we determined sex differences in the prevalence of these complaints.CONCLUSION:Complaints about poor sleep quality are quite common in patients with primary headache disorders and have sex and age differences. Identification of the described complaints of poor sleep quality is a simple tool for the initial analysis of sleep disorders in the practice of any specialist. We recommend paying great attention to these complaints for further diagnostics of sleep disorders and their timely treatment.

Roughly one-third of migraine patients suffer from migraine with aura, characterized by transient focal neurological symptoms or signs such as visual disturbance, sensory abnormalities, speech problems, or paresis in association with the headache attack. Migraine with aura is associated with an increased risk for stroke, epilepsy, and with anxiety disorder. Diagnosis of migraine with aura sometimes requires exclusion of secondary causes if neurological deficits present for the first time or are atypical. It was the aim of this review to summarize EEG an MRI findings during migraine aura in the context of pathophysiological concepts. This is a narrative review based on a systematic literature search. During visual auras, EEG showed no consistent abnormalities related to aura, although transient focal slowing in occipital regions has been observed in quantitative studies. In contrast, in familial hemiplegic migraine (FHM) and migraine with brain stem aura, significant EEG abnormalities have been described consistently, including slowing over the affected hemisphere or bilaterally or suppression of EEG activity. Epileptiform potentials in FHM are most likely attributable to associated epilepsy. The initial perfusion change during migraine aura is probably a short lasting hyperperfusion. Subsequently, perfusion MRI has consistently demonstrated cerebral hypoperfusion usually not restricted to one vascular territory, sometimes associated with vasoconstriction of peripheral arteries, particularly in pediatric patients, and rebound hyperperfusion in later phases. An emerging potential MRI signature of migraine aura is the appearance of dilated veins in susceptibility-weighted imaging, which may point towards the cortical regions related to aura symptoms ("index vein"). Conclusions: Cortical spreading depression (CSD) cannot be directly visualized but there are probable consequences thereof that can be captured Non-invasive detection of CSD is probably very challenging in migraine. Future perspectives will be elaborated based on the studies summarized.

BACKGROUND AND PURPOSE:Hormonal replacement therapy (HRT) is used for symptomatic treatment of menopause. Some evidence suggests a proconvulsant effect of estrogen and an anticonvulsant role of progesterone. Thus, the use of exogenous sex steroid hormones might influence the course of epilepsy in peri- and postmenopausal women with epilepsy (WWE). We conducted a systematic review on the impact of HRT on the frequency of seizures of WWE. METHODS:PubMed and Scopus were searched for articles published from inception until August 2022. Abstracts from the past 5 years from the European Academy of Neurology and European Epilepsy Congresses were also reviewed. Article reference lists were screened, and relevant articles were retrieved for consultation. Interventional and observational studies on WWE and animal models of estrogen deficiency were included. Critical appraisal was performed using the revised Cochrane risk-of-bias tool for randomized trials and ROBINS-E tool. RESULTS:Of 497 articles screened, 13 studies were included, including three human studies. One cross-sectional study showed a decrease in seizure frequency in WWE using combined HRT, a case-control study showed an increase in comparison with controls, and a randomized clinical trial found a dose-dependent increase in seizure frequency in women with focal epilepsy taking combined HRT. Ten studies addressing the impact of HRT in rat models were also included, which showed conflicting results. CONCLUSIONS:There is scarce evidence of the impact of HRT in WWE. Further studies should evaluate the harmful potential, and prospective registries are needed for monitoring this population.

Background Direct comparisons of the tolerability and safety of migraine preventive treatments targeting the calcitonin gene-related peptide pathway are lacking. This study aimed to compare the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies and gepants in migraine prevention. Methods A network meta-analysis of phase 3 randomized controlled trials assessing the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies (erenumab, eptinezumab, fremanezumab, or galcanezumab) and gepants (atogepant, rimegepant) in migraine prevention was performed. Primary outcomes were treatment-emergent adverse events and serious adverse events. Secondary outcomes included any adverse events, adverse events leading to treatment discontinuation and individual adverse events. Results We included 19 randomized controlled trials, comprising 14,584 patients. Atogepant 120 mg (OR 2.22, 95% CI [1.26, 3.91]) and galcanezumab 240 mg (OR 1.63, 95% CI [1.33, 2.00]) showed the largest odds of treatment-emergent adverse events compared to placebo. While eptinezumab 30 mg had greater odds of adverse events leading to treatment discontinuation (OR 2.62, 95% CI [1.03,6.66]). No significant differences in serious adverse events were found between active treatments and placebo. Eptinezumab was associated with the lowest odds of treatment-emergent adverse events and serious adverse events compared to placebo, whereas erenumab was associated with the lowest odds of any adverse events and quarterly fremanezumab with the lowest odds of treatment discontinuation due to adverse events. Conclusion Monoclonal antibodies targeting the calcitonin gene-related peptide pathway and gepants are a safe and well tolerated option for migraine prevention.

Background. Although persistent headaches are a common post-stroke pain syndrome, the epidemiology and clinical features of persistent headache after first-ever ischemic stroke have not been considered previously. There is no exact data on how often headache attributed to stroke persists for more than 3 months, i.e. meets the criteria for persistent headache after stroke and what are their distinctive clinical features. The tasks of our study were: to analyze the occurrence/incidence of persistent headaches after the first-ever ischemic stroke; to determine clinical characteristics and types of persistent headaches in comparison with headaches at the onset of stroke. Materials and methods. The study included 550 patients (mean age 63.1 years, 54% men) with first-ever ischemic stroke, of which 529 patients were followed up for at least three months after the stroke. Standardized semi-structured interview forms were used to assess these headaches during professional face-to-face interviews at the onset of stroke and 3 months after the stroke using telephone interview by neurologist. Results. Among 529 follow up patients 55 (10.4%) had persistent headaches after first-ever ischemic stroke. Among these 55 patients 34 patients had persistent new-type headaches which arose for the first time during the onset of stroke, they included predominated migraine-like headaches (n=20), tension-type-like headaches (n=9) and thunderclap-like headaches (n=5). 21 patients had persistent headaches with altered characteristics: predominated tension-type-like headaches (n=16), and less common migraine-like headaches (n=5). Persistent headaches after stroke had the following characteristics compared to headaches at onset of stroke: severe headache intensity, a gradual decrease of occurrence of accompanying symptoms (photo- and phonophobia; p=0.03), the transition of unilateral headaches in bilateral (p=0.004), the presence of headaches 15 days per month in 30.9% of the patients. Conclusion. Persistent post-stroke headaches represent a persistent pain syndrome with severe intensity and frequency of attacks, which requires their further study and creation of guidelines for their management.

Migrainous infarction (MI) is a rare disorder. The precise diagnostic criteria for this diagnosis have been available in the International Classification of Headache Disorders (ICHD) since 1988, but many cases do not fulfil these criteria. This paper describes a good example of MI and analyzes previously published case reports. We report a very special case of MI in an 18-year-old woman who had a recurrent episode of migraine with a similar aura with numbness of the right arm and speech disturbances which had an unusually long duration (>120 min). On admission to the headache centre “Europe-Asia”, she complained of slowness of speech and problems with choice of words. An MRI showed acute lacunar infarcts in the left parietal subcortical area. Ischemic infarcts were localized in a relevant area on the left side and the aura symptoms were right-sided. The patient, therefore, fulfilled the ICHD-3 diagnostic criteria for “Migrainous infarction”. An analysis of 35 previously published articles with case reports about MI showed that 22 did not meet the diagnostic criteria of the ICHD for migrainous infarction. Using all this, we developed diagnostic recommendations for migrainous infarction which can help to improve the quality of diagnosis when used together with the diagnostic criteria of the ICHD for migrainous infarction.

The chemical composition, distribution, and abundance of physiological groups of bacteria in thermal waters and microbial mats formed in the Nachikinsky, Malkinsky, and Verkhne-Paratunsky springs were studied. The degree of accumulation of microelements and formation of minerals by microbial mats of Kamchatka’s thermal springs was also analyzed. The study shows that the waters are characterized by different chemical composition, temperature, and pH content. The thermal waters under study show a low composition and numbers of functional groups of bacteria with the predominance of thionic bacteria. Prevalence of saprophytic, thionic, sulfate-reducing, manganese-oxidizing, ammonifying and nitrifying microorganisms in microbial mats was registered. The relevance of formed microbial mats in the concentration of many heavy metals, alkaline and alkaline earth elements was shown. Thus, cobalt, vanadium and thorium (Nachikinsky), cobalt, samarium and yttrium (Malkinsky), thorium, erbium and gallium (Verkhne-Vilyuchinsky) were most concentrated in microbial mats of Kamchatka’s hydrotherms. All studied microbial communities show the lowest accumulation of Li (1.39–2.97), Rb (1.91–2.67), Sr (2.67–2.80), Cs (1.91–3.04) and As (2.34–3.10). The formation of minerals was found in algo-bacterial mats: quartz, plagioclase, anorthite, calcite, and magnetite.

Migraine is one of the leading causes of disability worldwide, especially in women younger than 50 years old. Migraine has three times higher prevalence in women than in men and tends to decrease after the menopausal transition. Migraine has different clinical features in people of different ages. Clinical symptoms and factors associated with migraine can be various in women and men. Women have special types of migraine, such as pure menstrual migraine and menstrually related migraine. Besides, clinical symptoms of migraine can change during pregnancy, postpartum and lactation. Women are significantly more often than men consulting a doctor because of migraine. These features of migraine lead to different treatment and management strategies in females and males of different ages. Migraine therefore is a disorder that demonstrates the necessity of a personalization of healthcare-ensuring the proper treatment for the right patient, at the right time. Considering all the available literature and guidelines, in this chapter several strategies for management of acute and prophylactic treatments of migraine, according to sex and age differences, are discussed. The purpose of this chapter is to provide a useful piece of information improving the treatment and management of migraine.