MTNR1A and MTNR1B Gene Variants of the Melatonin Receptor and Arterial Stiffness in Persons without Arterial Hypertension.

A comparative analysis of vascular stiffness indices and the results of blood test was carried out in 85 healthy donors aged 19-64 years, carriers of polymorphic variants of type 1 and type 2 melatonin receptor genes. The associations of polymorphic markers of type 1 MTNR1A (rs34532313) and type 2 MTNR1B (rs10830963) melatonin receptor genes with parameters of vascular stiffness and blood parameters in healthy patients were studied. Genotyping was performed using allele-specific PCR. In all patients, 24-h BP monitoring with assessment of arterial stiffness was performed. Allele C homozygotes of MTNR1A differed significantly from carriers of the major T allele by elevated triglyceride, LDL, and fibrinogen levels. The major allele C of the rs10830963 polymorphic variant of the MTNR1B gene is associated with elevated LDL and triglycerides, as well as with individual differences in the elastic properties of the vascular wall in the examined subjects.

[Adjunctive therapy for sleep disorders]. / Vozmozhnosti ad"yuvantnoi terapii rasstroistv sna.

The article describes pathogenetic models for insomnia: «3P¼ model of insomnia, hyperarousal model, and sleep reactivity to stress model. Anxiety and stress are addressed as predisposing, precipitating and perpetuating factors of insomnia. The problem of high comorbidity of insomnia and mental disorders is highlighted. Modern non-pharmacological and pharmacological approaches to treatment of insomnia are described: psychotherapy, other non-pharmacological methods as well as the use of medications. These methods can be used both independently and in combination. In particular, combination of psychotherapy and nonprescription medicines aimed at normalizing emotional state is possible.

[Brain damage in sleep-disordered breathing: the role of glia (clinical aspects)]. / Povrezhdenie golovnogo mozga pri rasstroistvakh dykhaniya vo sne: rol' glii (klinicheskie aspekty).

Sleep-disordered breathing (SDB) is one of the most frequent sleep-wake disorders. SDB is associated with brain damage that manifests as structural (atrophy of amygdala, hippocampus, insula) and functional (cognitive and emotional dysfunction) disorders. In this review, we summarize the results of clinical and experimental studies investigating the approach for the decreasing brain damage in SDB via glial modulation. In conclusion, we suggest the strategies for future research aimed at optimizing diagnostics and treatment of brain damage in SDB.

[Brain damage in sleep-disordered breathing: the role of glia]. / Povrezhdenie golovnogo mozga pri narusheniyakh dykhaniya vo sne: rol' glii.

Sleep-disordered breathing (SDB) is one of the most prevalent sleep-wake disorders and is associated with brain damage. In this review, we describe the role of astroglia, microglia and oligodendroglia as the main cellular mediators of brain damage in SDB based on the results of experimental studies. Specifically, we describe the role of the molecules that are expressed by glia and mediate oxidative stress (NADPH-oxidase), inflammation (hypoxia-inducible factor-1, inducible nitric oxide synthase, pro- and anti-inflammatory cytokines) and sympathetic hyperactivation (ATP, lactate).

[Self-reported sleep and wake disorders in patients with ostheoarthrosis and end-stage renal disease]. / Sub"ektivnye narusheniya sna i bodrstvovaniya u patsientov s osteoartrozom na fone khronicheskoi bolezni pochek S5d stadii.

OBJECTIVE: This study aimed to assess subjective sleep and wake disorders (SWD) in patients with osteoarthritis and comorbid end-stage renal disease (ESRD) receiving hemodialysis (ESRD-HD) compared to patients with osteoarthritis and without chronic kidney disease (CKD) as well as to clarify of the association of subjective sleep characteristics with the levels of anxiety and depression and pain, general health score and laboratory parameters in these cohorts. MATERIAL AND METHODS: This pilot case-control study included the patients with stage III hip osteoarthritis with ESRD-HD (n=19) and without CKD (n=19) aged 18-85 years. The patients received the consultations of orthopedic surgeon and internal medicine specialist with anthropometry and clinical and biochemical blood tests. Subjective SWD were assessed with Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), Insomnia Severity Index (ISI), diagnostic criteria for restless legs syndrome (RLS) and Berlin questionnaire. Anxiety and depression were assessed with Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory (BDI). Subjective general health and osteoarthritis-related pain were assessed with visual analog scales (VAS). RESULTS: Compared to the patients with osteoarthritis and without CKD, the patients with osteoarthritis and ESRD-HD had a lower VAS score for general health (50.00 (40.00-75.00) points and 80.00 (70.00-80.00) points, p=0.014), a higher PSQI (12.0 (8.5-14.5) points and 8.0 (6.0-11.0) points, p=0.046), a higher incidence of RLS (59% and 16.8%, p=0.017) and a lower level of anxiety according to HADS (0.0 (0.0-3.0) points and 3.0 (2.0-5.5) points, p=0.025). The correlation and regression analysis showed the association of PSQI score with VAS score for general health (b= -1.7 points, p=0.002 with adjustment for age, sex and ESRD-HD), as well as the association of SWD with laboratory markers (PSQI score with creatinine level, FSS with eosinophil count, RLS with creatinine, urea and potassium levels). CONCLUSION: The results of our study demonstrated the high incidence of SWD in patients with osteoarthritis. These SWD have complex pathogenesis and require specific approach in patients with osteoarthritis and ESRD-HD.

[Sleep-wake cycle regularity and cardiometabolic indicators]. / Regulyarnost' ritma «son ­ bodrstvovanie¼ i kardiometabolicheskie pokazateli.

OBJECTIVE: To evaluate the association between sleep-wake rhythm and cardiometabolic parameters. MATERIAL AND METHODS: 103 participants, aged 25-64 years, underwent actigraphy study with Actigraph Actilife GT3X + device (USA) for 7 days. We assessed actigraphy indicators (physical activity and sleep data), anthropometric indicators, blood pressure and laboratory parameters. Actigraphy data was processed using the nparACT package in the R program with the calculation of nonparametric indicators: intraday variability, interday stability, the average level of lowest activity for five hours (L5) and ten hours with the highest activity (M10), relative amplitude is the ratio of M10/L5. RESULTS: The nonparametric analysis showed an association of the higher night activity with sleep effectiveness, wake after sleep onset, indicators of physical activity. A more stable sleep pattern is associated with more steps, less weight and waist circumference, lower levels of diastolic blood pressure, creatinine and insulin. Increased fragmentation of sleep patterns is associated with increased CRP and increased sedentary time. Participants with higher activity contrast have less waist circumference, hips and body mass index, lower levels of CRP and insulin. CONCLUSIONS: Rhythm and quality of sleep are important parameters associated with cardiometabolic indicators. Stable sleep patterns, higher activity during the day and lower night activity are associated with a more favorable condition of cardiovascular system.

[Sleep disordered breathing in patients with chronic heart failure: prognosis and management]. / Narusheniya dykhaniya vo vremya sna u patsientov s khronicheskoi serdechnoi nedostatochnost'yu: prognoz i vozmozhnosti terapii.

Sleep disordered breathing is a frequent comorbidity (50-75%) in patients with chronic heart failure, but it is usually underestimated. This review analyzes sleep disordered breathing in patients with chronic heart failure, demonstrates pathogenetic relationships and the prognostic role of sleep apnea. The authors present modern treatment options for sleep apnea in this cohort (from non-invasive ventilation to implantable devices), highlight the role of drug therapy and outline perspectives of different treatment approaches. This clinical problem is designated as multidisciplinary, which requires a dialogue between researchers and doctors of various specialties to organize comprehensive effective care for this cohort of patients.

[Multifunctional Monitoring: is it Possible to Simultaneously Evaluate Blood Pressure and Sleep-Disordered Breathing?]

Objective Carry out a comparative assessment of respiratory performance, based on multifunctional monitoring (MFM) and the recommended practice for complete polysomnography (PSG), and evaluate the effect of the blood pressure (BP) measurements in MFM on the quality of sleep.Materials and Methods At the first stage, 22 healthy volunteers (control group) underwent concomitant PSG and MFM, and 14 patients with suspected sleep-disordered breathing (SDB) underwent only PSG. At the second stage, concomitant PSG and MFM were performed in patients with confirmed SDB.Results In the control group, MFM detected a lower level of SpO2, a lower desaturation index (DI), and a higher apnea index (AI) than in the PSG group. However, the apnea-hypopnea index (AHI) was comparable in both groups. During concomitant PSG-MFM, the measurements of BP increased the number of micro-arousals only in the SDB group.Conclusion Results of the assessment of respiratory performance in MFM are comparable in both groups. The detected features of MFM indicators in the evaluation of the chest movements using rheopneumography, criteria different from that generally used for desaturation and hypoxemia, can lead to underestimation of desaturation and DI and underestimation of AI in the control group. The measurements of BP during sleep induced micro-arousals in the SDB group.

[Obstructive sleep apnea syndrome and cognitive impairment]. / Cindrom obstruktivnogo apnoé sna i kognitivnye narusheniia.

Sleep-disordered breathing is associated with sleep fragmentation and reduced blood oxygenation due to apnea and hypopnea episodes. Multiple studies indicate that obstructive sleep apnea syndrome (OSAS) can have negative impact on cognitive functioning, primarily executive functions, attention, and episodic memory. The attention is also focused on cognition in patients with neurologic and psychiatric comorbidities. There are different explanatory models, which show the mechanisms of OSAS influence on cognition. However, it is still unclear how the initial severity of the disease and clinical outcomes interrelate, and which factors play role in the compensation of cognitive dysfunction. Better understanding of these issues is crucial for the prevention of cognitive impairment and rehabilitation of cognitive functioning.

[Sleep disorders and stroke: data of the esse-rf study]. / Narusheniia sna i insul't: dannye issledovaniia ÉSSE-RF.

AIM: To assess the association between stroke and self-reported sleep disorders in the epidemiological studies of cardiovascular diseases in various regions of Russia (ESSE-RF). MATERIAL AND METHODS: A questionnaire survey included unorganized male and female population, aged 25 to 64 years, from 13 regions of the Russian Federation. In the analysis, answers to the question related to history of stroke: 'Did the doctor ever tell you that you had / had the following diseases?' (the 'Diseases' module) were included. The authors also evaluated answers about sleep duration, insomnia complaints, and sleepiness (the 'Sleep assessment' module). RESULTS AND CONCLUSION: Of 20 357 respondents, 422 (2%) confirmed the history of stroke. Both short and long sleep duration were not associated with stroke. Complaints of sleep disorders (snoring, sleep apnea, difficulty falling and maintaining sleep, as well as their combinations) were more frequently correlated with stroke. After adjustment for gender, age, body mass index, office blood pressure, the regression analysis showed that odds ratio was not significant for all complaints, except the combination of sleep apnea with frequent daytime sleepiness (1.7 (95% CI 1.04-2.8) (p=0.034). Therefore, symptoms of sleep-disordered breathing and insomnia are more common in respondents with the history of stroke. The combination of sleep apnea and frequent sleepiness complaints may indicate more severe sleep disorders in post-stroke patients.

[Social-demographic aspects of insomnia in the Russian population according to ESSE-RF study]. / Sotsial'no-demograficheskie aspekty insomnii v rossiiskoi populiatsii po dannym issledovaniia ÉSSE-RF.

AIM: To estimate the prevalence of insomnia symptoms and their association with socio-demographic characteristics in the regions participated in the study. MATERIAL AND METHODS: Data from participants of the cohort study Epidemiology of cardiovascular disease in various regions of the Russian Federation (ESSE-RF), aged 25-64 years, from 13 regions of the Russian Federation were analyzed. They were interviewed about sleep complaints: difficulties falling asleep, maintaining sleep, sleepiness and sleeping pill intake (response variants: never, less than once a week, 1-2 times a week, three and more times a week). Responses with complaints occurring at least three times a week were considered as insomnia symptoms. Social and demographics characteristics from survey included: age, gender, education, marital status, job/employment, type of housing. The final analysis included 20 359 respondents. RESULTS: Clinically significant frequent (≥3 times a week) difficulties of falling asleep were reported by 17.2% respondents, difficulties in maintaining sleep by 13.6%; drowsiness by 6.3%, taking sleeping pills by 2.9% respondents. Women reported sleep complaints twice more after comared to men. The occurrence of frequent difficulties to falling asleep and nocturnal awakenings increased with age - from 11.4% and 5.9% to 24.2% and 20.7%. The highest occurrence of insomnia symptoms to such as difficulties in falling asleep and nocturnal awakenings was found in women, older age groups, divorced subjects or living separately, those with primary education, retired or disabled and living in a communal apartment or 'other' type of housing. CONCLUSION: Symptoms of insomnia are widespread among participants of the ESSE-RF study and associated with socio-demographic characteristics. Groups with high risk of insomnia include women, older age groups, divorced or living separately, those with primary education, unemployed pensioners and people with disabilities living in a communal apartment or 'other' type of housing.

[Stress levels and coping behavior in patients with chronic insomnia]. / Uroven' stressa i stress-preodolevaiushchee povedenie u patsientov s khronicheskoi insomniei.

AIM: To assess stress level and coping strategies in chronic insomnia as its potential psychological factors. MATERIAL AND METHODS: The study group included 29 patients (19 women), aged 18-55 years old (mean age 33.1±2.1 years), with chronic insomnia diagnosed in accordance with the International Classification of Sleep Disorders III. The control group was formed by 32 subjects (11 men), aged 18-55 years old (mean age 31.5±2.0 years), without sleep disorders. Insomnia Severity Index and polysomnography were used to evaluate sleep quality. Stress level and coping strategies were assessed via an interview (stressfull life events during last year, their duration, their controllability, unexpectedness, and outcome), and by 'Level of subjective control' and 'Ways of coping questionnaires'. RESULTS: Both groups were comparable by the mean number of significant events during last year (4.97±0.34 vs 4.72±0.23, p=0.54). Patients with insomnia more often reported the loss of a relative (p=0.04), while controls more frequently reported positive events, such as pregnancy (p=0.007) or wedding (p=0.02) among close ones. Insomniacs more often described the stressful events as uncontrolled (p<0.001) and prolonged (p<0.001). They demonstrated lower indices of all the scales of the 'Level of subjective control', questionnaire except the scale of interpersonal attitudes. They rarely implemented confrontive coping (p=0.001), seeking social support (p<0.001), accepting responsibility (p<0.001) and positive reappraisal (p<0.001). CONCLUSIONS: The interpretation of stressful events and personal response in insomnia patients might be considered as psychological risk factors for insomnia development.

[The role of subjective methods for the evaluation of sleep quality]. / Opredelenie roli sub''ektivnykh metodov obsledovaniia v otsenke kachestvennykh kharakteristik sna.

AIM: To assess the accuracy of questions evaluating the quality and duration of sleep. MATERIAL AND METHODS: Target population included residents of St. Petersburg, who participated in the epidemiological study ESSE-RF. Out of 1417 participants, 136 individuals agreed to undergo additional sleep evaluation, and 49 subjects underwent polysomnography study for objective sleep evaluation. All participants were interviewed for subjective sleep assessment (standard questionnaires and Pittsburgh sleep quality index questionnaire). RESULTS: One third of the participants evaluated sleep quality in the lab worse than at home. Their sleep duration was 1,5h shorter than in those who reported sleep quality to be as good as at home. However, the majority of participants slept in the sleep lab more than at home for the previous month. Moreover, 59% subjects reported sleep disturbances. Sleep duration during night in the lab was 6.6 [3; 9] - vs. 7 [3; 10] hours as assessed by PSG and by subjective report, respectively (p=0,06). At the same time, usual average sleep duration was 8 [5; 10] hours (p=0.005), and average sleep duration during last month - 7 [5; 9] hours. CONCLUSION: One third of subjects report worse sleep in the laboratory compared to the usual nights and it is associated with their subjective shorter sleep duration. Subjective assessment of sleep duration and sleep onset time is appropriate for sleep evaluation during the last night, unlike subjective assessment of awakenings after sleep onset. Average self-reported sleep duration depends on the question formulation.

[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.

[Clinical features of obstructive sleep apnea syndrome in patients with acromegaly].

AIM: To investigate the incidence of sleep-related breathing disorders (SRBDs) in patients with active acromegaly (AM), to specify risk factors influencing apnea/hypopnea index (AHI), and to reveal the specific features of obstructive sleep apnea (OSA) in patients with AM versus those with OSA without AM. SUBJECTS AND METHODS: Fifty patients with active AM were examined and divided into 3 groups: control group 1 did not differ from the study group in body mass index (BMI); control group 2 did not similar in AHI from the AM group. Polysomnography was done in all the patients. RESULTS: SRBDs were detected in 40 (80%) patients. Obstructive apnea was found in all cases. Correlation analysis revealed the relationships between AHI and gender (AHI was higher in the men), BMI, disease duration, and insulin-like growth factor 1 (GF-1). There were no correlations between AHI and gender, maximum adenoma size, and growth hormone levels. Compared with control group 1, the AM group had a statistically significantly higher median AHI [16 (1-92) and 4.7 (0-31.3) episodes per hour of sleep (p < 0.001)]. In control group 2, the median BMI was considerably higher than in the control group [29.2 (19.9-44.3) and 35 (24-56) kg/m2 (p < 0.001). CONCLUSION: The detection rate of SRBDs in patients with active AM was 80%, with obstructive disorders being prevalent. There was a positive relationship between SRBD severity and BMI, AM duration, IGF-1 level. Compared to the controls, the patients with AM developed SRBDs similar in severity with lower BMI; severer SRBDs were detected in the patients with active AM with the similar BMI.