[Association of inflammation and chronic fatigue syndrome in patients with Parkinson's disease]. / Assotsiatsiya vospaleniya i sindroma khronicheskoi ustalosti pri bolezni Parkinsona.

OBJECTIVE: To study the prevalence of chronic fatigue syndrome (CFS) and association of CFS with other clinical and neuropsychological manifestations of Parkinson's disease (PD) as well as with serum inflammatory markers and genetic polymorphisms. MATERIAL AND METHODS: The study included 533 patients with PD. All patients underwent clinical, neurological examination and neuropsychological testing using validated questionnaires: MoCA test, HADS, BDI-II, the Fatigue Severity Scale (FSS). Serum concentrations of inflammatory markers (slCAM-1, sVCAM-1, NCAM, CCL5, PAI-1 and MPO) were assessed in 144 patients using xMAP technology. A case-control study of CCL5 (rs2107538) and PAI-1 (rs2227631) gene polymorphisms was performed in connection with PD development and in groups differing in the presence/absence of CFS in PD. In addition, the relationship of these polymorphisms with variability in the levels of the corresponding proteins in the blood serum of patients was studied. Genotyping of CCL5 (rs2107538) and PAI-1 (rs2227631) polymorphisms was performed using real-time PCR with TaqMan probes. RESULTS: CFS is common in 66.7% of patients in the PD group. In addition, non-motor symptoms (emotional-affective, cognitive, autonomic disorders and pain) were more common in patients with CFS. A strong correlation has been established between the severity of CFS assessed with FSS and serum concentrations of CCL5, sVCAM-1, NCAM and slCAM-1. In newly diagnosed patients with PD who were not taking antiparkinsonian drugs at the time of the study and had CFS, higher correlations were noted between inflammatory markers and the severity of CFS manifestations. When comparing the distribution of genotypes and alleles of CCL5 (rs2107538) and PAI-1 (rs2227631) polymorphisms, some differences were found between the groups of patients with PD and controls (p<0.05). However, these polymorphisms did not affect the variability of serum protein levels CCL5 and PAI-1, respectively, nor did they affect the development of CFS in patients with PD. CONCLUSION: CFS is common in PD, and patients with PD and CFS are characterized by elevated levels of serum markers CCL5, sVCAM-1, slCAM-1 and NCAM, suggesting the importance of the inflammatory component in the development of neurodegenerative disease. In addition, the clinical course of PD in patients with CFS is aggravated by other non-motor manifestations, including emotional-affective, cognitive, autonomic disorders and pain. These results highlight the potential contribution of an inflammatory component to the development of fatigue associated with PD, starting from the earliest clinical stages of the disease.

[Growth factors PDGF-AA, PDGF-BB and BDNF as potential differentiating biomarkers of unipolar and bipolar depression]. / Faktory rosta PDGF-AA, PDGF-BB i BDNF kak potentsial'nye differentsiruyushchie biomarkery monopolyarnoi i bipolyarnoi depressii.

OBJECTIVE: To establish the differences and identify the prognostic value of biological markers - platelet growth factors PDGF-AA, PDGF-BB and brain-derived neurotrophic growth factor (BDNF) - for the differential diagnosis of patients with unipolar and bipolar depression using machine learning. MATERIAL AND METHODS: The study included 79 patients aged 48 [34; 57] years, including 35 people with bipolar depression (ICD-10. F31) and 44 people with unipolar depression (F32-33). Clinical assessment of the patients' condition was carried out using the Hamilton Depression Rating Scale (HDRS-17) and the Hamilton Anxiety Rating Scale (HARS). The concentration of growth factors in the blood serum of patients was determined using multiplex analyzers Magpix and Luminex 200 (Luminex, USA). To build a predictive model, the support vector machine was used. RESULTS: Patients with bipolar depression showed statistically significant higher concentrations of PDGF-AA and PDGF-BB, as well as lower concentrations of BDNF. When constructing a predictive model, it was possible to separate patients with unipolar and bipolar depression according to all three biomarkers; the sensitivity and specificity of the model were 0.96±0.06 and 0.95±0.05, respectively. CONCLUSIONS: The study of concentrations of BDNF and platelet-derived growth factors shows statistically significant differences in indicators in the case of unipolar and bipolar depression, which can potentially be used as prognostic biomarkers for differential diagnosis in appropriate clinical cases.

[Associations of serum neuromarkers with clinical features of Parkinson's disease]. / Assotsiatsii syvorotochnykh neiromarkerov s klinicheskimi osobennostyami bolezni Parkinsona.

OBJECTIVE: To evaluate the clinical and laboratory correlation of biomarkers with anti- and pro-apoptotic activity with the severity of motor and non-motor symptoms depending on the progression rate of Parkinson's disease (PD). MATERIAL AND METHODS: A wide range of non-motor symptoms (emotional-affective, cognitive, psychotic and behavioral disorders, fatigue, sleep disorders and autonomic disorders) was evaluated using validated scales and a number of serum neuromarkers responsible for neuroplasticity and neuronal survival processes (BDNF, PDGF, cathepsin D) in 71 patients with PD (mean age 65 (55; 70) years, disease duration 7 (4; 9) years, age of onset 57 (49; 62) years). RESULTS: The concentration of biomarkers (BDNF, PDGF and cathepsin D) was the lowest in the group of patients with a rapid PD progression rate (p<0.001, p=0.001 and p=0.031, respectively), the severity of motor and most non-motor symptoms was higher (p=0.023 and p=0.001, respectively) compared to middle and slow progression rate. There were correlations between BDNF concentration and the severity of depression (r=-0.63, p<0.001), apathy (r=-0.48, p<0.001), impulsive behavioral disorders (r=0.500, p<0.001), level of cognitive functions (r=0.54, p<0.001), motor symptoms (r=-0.43, p<0.001); between PDGF level and the severity of motor manifestations of PD (r=-0.30, p=0.011), depression (r=-0.70, p<0.001), apathy (r=-0.460, p<0.001), the degree of severity of behavioral disorders (r=0.742, p<0.001). No significant correlations were observed between the level of cathepsin D and the severity of clinical manifestations of PD, which indicates the connection of cathepsin D with the general pathogenesis of PD. CONCLUSION: The possibility of using serum proteins of the neurotrophin subfamily and the protein associated with autophagy, cathepsin D, as biomarkers that determine the prognosis of PD, is considered.

[Associations between components of metabolic syndrome and cognitive impairment in patients with schizophrenia]. / Svyazi mezhdu komponentami metabolicheskogo sindroma i kognitivnymi narusheniyami u bol'nykh shizofreniei.

OBJECTIVE: To study the relationship between the individual components of the metabolic syndrome and cognitive dysfunction in patients with schizophrenia. MATERIAL AND METHODS: A total of 133 patients with schizophrenia were examined. To assess cognitive functioning, the Brief Assessment of Cognition in Schizophrenia (BACS) was used. The components of the metabolic syndrome were determined in accordance with the criteria of the International Diabetes Federation. RESULTS: Hyperglycemia in patients with schizophrenia led to a decrease in cognitive functioning in two domains: verbal fluency (ß=-10.67; p=0.019) and attention stability (ß=-9.519; p=0.043). Abdominal obesity was associated with lower indicators of executive functions (ß=-8.856; p=0.026). CONCLUSION: It is assumed that drug treatment of some components of the metabolic syndrome may affect cognitive functions in patients with schizophrenia.

[Serum neurofilament light chains in assessing the course of multiple sclerosis]. / Syvorotochnye legkie tsepi neirofilamentov v otsenke techeniya rasseyannogo skleroza.

OBJECTIVE: To study a role of serum neurofilament light chains (sNFL) in assessment of course and progression of multiple sclerosis (MS) in the population of patients with MS in the Tomsk region. MATERIAL AND METHODS: The study involved 93 patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) (nRRMS=75, nSPMS=18). The study was carried out in a two-stage design: the first stage was a cross-sectional study for the entire sample; the second stage was a prospective observation with two visits for patients with relapse. sNFL concentration was determined by solid-phase ELISA. RESULTS: There was no statistically significant difference between RRMS and SPMS, and relapse and remission groups in terms of sNFL levels. Patients with a MS duration exceeding 14 years had higher rates of sNFL than those with a shorter duration (p=0.02). The subjects of the second study stage showed a decrease in sNFL from 2.05 (1.86; 2.19) pg/ml to 1.92 (1.87; 2.04) pg/ml (p=0.005), and slowdown in sNFL reduction correlated with the severity of cognitive impairment (k=0.52; p<0.05). CONCLUSION: Dynamic monitoring of sNFL allows the evaluation of the activity of the disease, as well as making an assumption about the compensatory possibilities of subsequent recovery.

[The relationship between the rs6265 polymorphism of the BDNF gene and the level of serum neurotrophic factor in patients with Parkinson's disease]. / Svyaz' polimorfizma rs6265 gena BDNF s urovnem syvorotochnogo neirotroficheskogo faktora u patsientov s bolezn'yu Parkinsona.

OBJECTIVE: To evaluate the clinical features and the level of serum brain-derived neurotrophic factor (BDNF) in groups of patients with Parkinson's disease (PD) differentiated by the genotypes of BDNF polymorphism (rs6265). MATERIAL AND METHODS: The level of serum BDNF in the biomarkers' multiplex panel of neurodegenerative diseases (HNDG3MAG-36K) was assessed in 134 PD patients. Allele discrimination was carried out by real-time PCR using TaqMan probes for the analysis of BDNF rs6265 polymorphism in groups of patients and controls (n=192) matched for sex, age and ethnicity. RESULTS: Comparing the distribution of rs6265 genotypes and alleles between groups of patients and controls no significant differences were found (p>0.05). Serum BDNF levels varied significantly by genotype (rs6265) among PD patients. Minimum mean serum BDNF level (320.1±164.6 pg/ml) was noted for individuals with the AA genotype, which significantly differs from the corresponding indicator among individuals with GA (2944.2±1590.6 pg/ml; p=0.0001) and GG genotypes (2949.4±1620.6 pg/ml; p=3.9×10-5). The concentration of BDNF significantly differed between patients with different forms of PD (p=0.0007) and increased as the stage of the disease progressed according to Hoehn and Yahr staging scale (p=1.0×10-6). CONCLUSION: The BDNF rs6265 polymorphism was not associated with the development of PD in the studied population. The variability of the mean serum BDNF level was established depending on the genotype of the BDNF polymorphism in PD patients and a number of clinical features.

Antimicrobial and antioxidant activity of Panax ginseng and Hedysarum neglectum root crop extracts / Atividade antimicrobiana e antioxidante de extratos de raízes de Panax ginseng e Hedysarum neglectum

In order to ensure the timely and uninterrupted supply of medicinal plant raw materials, the methods of cultivation of plant cell cultures, namely, the production of plant root cultures, are relevant. In this paper, the geroprotective potential of Hedysarum neglectum Ledeb and Panax ginseng C. A. Mey root cultures is studied. They were cultured under in vitro conditions by transforming the rhizome (H. neglectum) and seed seedlings (P. ginseng) with Agrobacterium rhizogenes 15834 Swiss. To identify the geroprotective potential, the antimicrobial disc-diffusion method and the antioxidant activity were analyzed by titration of KMnO4 extracts of plant root cultures. The qualitative and quantitative composition was analyzed using high-performance liquid chromatography, thin-layer chromatography, and gas chromatography with mass spectrometry. In the course of the work, the presence of antimicrobial and antioxidant activity of plant root culture extracts was established. Biologically active substances contained in extracts of Hedysarum neglectum Ledeb root crops and Panax ginseng C. A. Mey are characterized by geroprotective potential, so they can act as a source of natural antioxidants in the functional nutrition of the geroprotective orientation.

Para garantir o abastecimento em tempo e ininterrupto de matérias-primas de plantas medicinais, são relevantes os métodos de cultivo de culturas de células vegetais, nomeadamente a produção de culturas de raízes vegetais. Neste trabalho, foi estudado o potencial geroprotetor de culturas de raízes de Hedysarum neglectum Ledeb e Panax ginseng C. A. Mey. Eles foram cultivados em condições in vitro pela transformação do rizoma (H. neglectum) e mudas de sementes (P. ginseng) com Agrobacterium rhizogenes 15834 Swiss. Para identificar o potencial geroprotetor, o método antimicrobiano de difusão em disco e a atividade antioxidante foram analisados por titulação de extratos de KMnO4 de raízes de plantas. A composição qualitativa e quantitativa foi analisada por cromatografia líquida de alta eficiência, cromatografia em camada delgada e cromatografia gasosa com espectrometria de massa. No decorrer do trabalho, foi constatada a presença de atividade antimicrobiana e antioxidante dos extratos de raízes de plantas. Substâncias biologicamente ativas contidas em extratos de raízes de H. neglectum Ledeb e P. ginseng C. A. Mey são caracterizadas pelo potencial geroprotetor, podendo atuar como fonte de antioxidantes naturais na nutrição funcional da orientação geroprotetora.

Antimicrobial and antioxidant activity of Panax ginseng and Hedysarum neglectum root crop extracts

Abstract In order to ensure the timely and uninterrupted supply of medicinal plant raw materials, the methods of cultivation of plant cell cultures, namely, the production of plant root cultures, are relevant. In this paper, the geroprotective potential of Hedysarum neglectum Ledeb and Panax ginseng C. A. Mey root cultures is studied. They were cultured under in vitro conditions by transforming the rhizome (H. neglectum) and seed seedlings (P. ginseng) with Agrobacterium rhizogenes 15834 Swiss. To identify the geroprotective potential, the antimicrobial disc-diffusion method and the antioxidant activity were analyzed by titration of KMnO4 extracts of plant root cultures. The qualitative and quantitative composition was analyzed using high-performance liquid chromatography, thin-layer chromatography, and gas chromatography with mass spectrometry. In the course of the work, the presence of antimicrobial and antioxidant activity of plant root culture extracts was established. Biologically active substances contained in extracts of Hedysarum neglectum Ledeb root crops and Panax ginseng C. A. Mey are characterized by geroprotective potential, so they can act as a source of natural antioxidants in the functional nutrition of the geroprotective orientation.

Resumo Para garantir o abastecimento em tempo e ininterrupto de matérias-primas de plantas medicinais, são relevantes os métodos de cultivo de culturas de células vegetais, nomeadamente a produção de culturas de raízes vegetais. Neste trabalho, foi estudado o potencial geroprotetor de culturas de raízes de Hedysarum neglectum Ledeb e Panax ginseng C. A. Mey. Eles foram cultivados em condições in vitro pela transformação do rizoma (H. neglectum) e mudas de sementes (P. ginseng) com Agrobacterium rhizogenes 15834 Swiss. Para identificar o potencial geroprotetor, o método antimicrobiano de difusão em disco e a atividade antioxidante foram analisados por titulação de extratos de KMnO4 de raízes de plantas. A composição qualitativa e quantitativa foi analisada por cromatografia líquida de alta eficiência, cromatografia em camada delgada e cromatografia gasosa com espectrometria de massa. No decorrer do trabalho, foi constatada a presença de atividade antimicrobiana e antioxidante dos extratos de raízes de plantas. Substâncias biologicamente ativas contidas em extratos de raízes de H. neglectum Ledeb e P. ginseng C. A. Mey são caracterizadas pelo potencial geroprotetor, podendo atuar como fonte de antioxidantes naturais na nutrição funcional da orientação geroprotetora.

[Particularities of arterial stiffness dynamics on the background of breast cancer chemotherapy].

BACKGROUND: Modern breast cancer chemotherapy regimens (BC) consider individual patient parameters and ranges of cardiotoxic doses. However, clinicians often record clinical and laboratory-instrumental signs of cardio- and vasculotoxicity in patients, which emphasizes the high importance of searching for markers of early toxic response. AIM: To study the characteristics of the response of arterial stiffness on the background of anthracycline-containing chemotherapy to determine potential markers of vasculotoxicity in BC patients. MATERIALS AND METHODS: 20 women with a BC were included. The patients received 4 cycles of chemotherapy in the doxorubicin + cyclophosphane (AC) regimen with an interval of 2-3 weeks, then they were injected with paclitaxel weekly for 12 injections, or docetaxel once every 3 weeks. All patients underwent TTE, arterial stiffness determination by the "gold standard" method and using volumetric sphygmography before the start of treatment, after the completion of the anthracycline component and after the end of taxanes. RESULTS: The average age of the patients was 45.5±5.31 years. After completing the course of anthracyclines, there was a significant increase in heart rate (from 65.6±9.3 to 73.3±10.1 beats/min.), a decrease in SBP (from 122.6±9.9 to 116.5±12.3 mmHg) and DBP (from 78.9±8.5 to 76.2±8.6 mmHg), a decrease in carotid femoral pulse wave velocity (cfPWV) (from 9.32±1.41 to 7.85±1.57 m/s), CAVI index on the left (from 6.78±0.81 to 6.5±0.88), the velocity of the cardio-ankle pulse wave on the right and left (from 6.7±0.6 to 6.5±0.7 m/s; from 7.0±0.6 to 6.3±0.8 m/sc, respectively). After the completion of the taxane, there was a tendency to increase these indicators, however, they remained significantly lower compared to the values before the start of treatment. CONCLUSION: A comparative analysis of arterial stiffness indicators at different stages of chemotherapy showed a more pronounced reaction of cfPWV, CAVI, cardio-ankle pulse wave to the administration of anthracyclines, which presumably may be associated with concomitant hemodynamic restructuring.

Real-world effectiveness of fingolimod in patients with multiple sclerosis in Bulgaria. / Eficacia en la vida real del fingolimod en pacientes con esclerosis múltiple en Bulgaria.

INTRODUCTION: Fingolimod, a sphingosine-1-phosphate receptor agonist used for the treatment of multiple sclerosis (MS). Our goal was to assess the impact of fingolimod on quality of life in patients with relapsing-remitting multiple sclerosis (RRMS) after 2 years of treatment in this real-world study. PATIENTS AND METHODS: This was a 2-year, prospective, observational study conducted in Bulgaria in RRMS patients treated with fingolimod. Quality of life was assessed using the Bulgarian-language version of the MSQoL-54 scale. The primary endpoint was the change from baseline in the MSQoL-54 score after 2 years of treatment. Secondary endpoints included the change from baseline in the MSQoL-54 score after one year of treatment, furthermore the assessment of depression level using the Hamilton D-17 score. RESULTS: A total of 87 eligible patients were included in the study with a mean age of 38.7 ± 8.45 years. The median Expanded Disability Status Scale (EDSS) score was 3.5 points. We found statistically significant improvement in 10 subscales at month 12 and in seven subscales at month 24. The mental health composite score increased from 64.0 ± 16.69 points to 67.5 ± 15.94 points at month 24 (p = 0.012). The physical health composite score increased from 61.7 ± 17.61 to 66.3 ± 16.70 (p = 0.001). Depression level measured by the HAM-D17 decreased significantly by month 12 and month 24. The EDSS score decreased or remained stable in more than half of the patients (61.6%). We detected better quality of life in patients with a lower EDSS score. CONCLUSIONS: Quality of life scores and the depression level are improved in RRMS patients treated with fingolimod over 2 years in real-life setting.

TITLE: Eficacia en la vida real del fingolimod en pacientes con esclerosis múltiple en Bulgaria.Introducción. El fingolimod es un agonista del receptor de esfingosina-1-fosfato utilizado para el tratamiento de la esclerosis múltiple (EM). Nuestro objetivo era evaluar los resultados del fingolimod en la calidad de vida de los pacientes con EM recurrente-remitente tras dos años de tratamiento en este estudio de la vida real. Pacientes y métodos. Se trata de un estudio observacional prospectivo de dos años de duración realizado en Bulgaria en pacientes con EM recurrente-remitente tratados con fingolimod. Se evaluó la calidad de vida mediante la versión en búlgaro de la escala Multiple Sclerosis Quality of Life-54 (MSQoL-54). El criterio de valoración principal fue el cambio respecto al valor inicial en la puntuación en la MSQoL-54 tras dos años de tratamiento. Los criterios de valoración secundarios fueron el cambio respecto al valor inicial en la puntuación en la MSQoL-54 tras un año de tratamiento, además de la evaluación del nivel de depresión mediante la puntuación de la escala de puntuación de la depresión de Hamilton (HAM-D17). Resultados. En el estudio se incluyó a 87 pacientes elegibles con una edad media de 38,7 ± 8,45 años. La mediana de la puntuación en la Expanded Disability Status Scale (EDSS) fue de 3,5 puntos. Se halló una mejora estadísticamente significativa en 10 subescalas en el mes 12 y en siete subescalas en el mes 24. La puntuación combinada de salud mental aumentó de 64 ± 16,69 puntos a 67,5 ± 15,94 puntos en el mes 24 (p = 0,012). La puntuación combinada de salud física aumentó de 61,7 ± 17,61 a 66,3 ± 16,7 (p = 0,001). El nivel de depresión medido por la HAM-D17 disminuyó considerablemente en el mes 12 y en el mes 24. La puntuación de la EDSS disminuyó o se mantuvo estable en más de la mitad de los pacientes (61,6%). Detectamos una mejor calidad de vida en los pacientes con una puntuación más baja en la EDSS. Conclusiones. Las puntuaciones de calidad de vida y el nivel de depresión mejoraron en los pacientes con EM recurrente-remitente tratados con fingolimod durante dos años en un entorno real.

[BDNF gene RS6265 polymorphism in patients with multiple sclerosis of Tomsk region]. / Polimorfizm RS6265 gena BDNF v populyatsii bol'nykh rasseyannym sklerozom Tomskoi oblasti.

OBJECTIVE: To study the effect of the RS6265 polymorphism of BDNF gene on the risk of development, main clinical characteristics and DMT response in MS patients in Tomsk region. MATERIAL AND METHODS: The study group included 321 patients, the control group consisted of 266 healthy volunteers. Deoxyribonucleic acid (DNA) was isolated from venous blood using the standard phenol-chloroform method. Genotyping was carried out by real-time polymerase chain reaction (PCR) using competing TaqMan probes complementary to the polymorphic nucleotide sequence. RESULTS: Carriage of the C allele and CC genotype of the RS6265 polymorphism of the BDNF gene was found to be a factor determining a more favorable MS course. CONCLUSION: Carriers of the indicated genotype had a low rate of MS progression, a lower frequency of relapses and a less pronounced degree of disability with a comparable MS duration, and significantly more often demonstrated a more optimal response to first and second line of DMT.

[Coherence of the electroencephalogram and peripheral markers of nerve tissue damage in depressive disorders]. / Kogerentnost' elektroentsefalogrammy i perifericheskie markery povrezhdeniya nervnoi tkani pri depressivnykh rasstroistvakh.

OBJECTIVE: To evaluate the coherence parameters of the electroencephalogram and the level of peripheral markers of nerve tissue damage in patients with depressive disorders. MATERIAL AND METHODS: Thirty patients with a diagnosis from a cluster of mood disorders: affective disorder within a single depressive episode and recurrent depressive disorder were examined. A control group consisted of 30 healthy individuals, comparable in sex and age to the main group. The bioelectric activity of the brain was recorded and analyzed with the calculation of the averaged coefficients of intra- and interhemispheric coherence. The concentration of calcium-binding protein S100b, the main protein of myelin MBP and glial fibrillar acid protein GFAP was determined in blood sera by solid-phase enzyme immunoassay. RESULTS: Patients with depressive disorders showed signi cantly lower coefficients of interhemispheric coherence of alpha (p=0.003), beta (p=0.042) and theta rhythms (p=0.041), as well as intrahemispheric coherence of alpha rhythm in the left (p=0.016) and right hemispheres (p=0.026), beta rhythm in the right hemisphere (p=0.034) compared to the control group. Patients with depressive disorders showed a higher concentration of MBP compared to the control group (p=0.008). Additionally, we identified statistically significant correlations between EEG coherence coefficients and serum markers in patients with depressive disorders. CONCLUSION: The results clearly confirm the presence of inflammatory changes in the brain in patients with depression, which is reflected in structural and functional changes.

[Correlations between clinical features of bipolar affective disorder and serum concentrations of ANKRD12 gene product, coagulation factor XIII, and cadherin 5]. / Svyaz' kontsentratsii belka-produkta gena ANKRD12, XIII faktora koagulyatsii i kadgerina 5 v syvorotke krovi s klinicheskimi osobennostyami bipolyarnogo affektivnogo rasstroistva.

OBJECTIVE: To determine the serum concentrations of some proteins identified in the blood serum of patients with bipolar affective disorder (BD) and to evaluate the relationship of their concentrations with clinical characteristics of BD. MATERIAL AND METHODS: Protein concentrations of cadherin 5, coagulation factor XIII and ANKRD12 gene product in the blood serum of patients with BD and healthy individuals were determined using commercial ELISA kits. The severity of current depression and the main clinical manifestations of BD were assessed by SIGH-SAD and CGI upon admission to the hospital before the prescription of therapy. Data analysis was carried out using the Kruskal-Wallis and Mann-Whitney tests. RESULTS: Comparison between subgroups of BD patients, selected in accordance with the current affective episode (hypomanic, manic, depressive and mixed), and control group by the Kruskal-Wallis test has shown the significant difference in ANKRD12 protein product concentration (p=0.0448). When comparing pairwise each subgroup with the control group, the significant difference in ANKRD12 product concentration was found only in the case of a subgroup of BD patients with current depressive episode (Mann-Whitney test, p=0.006). Pairwise comparison of the ANKRD12 product concentrations in subgroups of BD patients with different disease duration (<5 years, 6-10 years, and >11 years) and in the control group by the Mann-Whitney test has revealed significant differences (p=0.04, p=0.01, p=0.02, respectively), the maximum protein concentration was found in patients with disease duration >11 years. Significant negative correlation of cadherin 5 concentration with the severity of atypical depressive symptoms assessed by SIGH-SAD (r=-0.69, p=0.038) and the decrease in cadherin 5 concentration in BD patients with greater severity of the current depressive episode were revealed. Significant negative correlation was found between factor XIII concentration and CGI scores (r=-0.62, p=0.032). CONCLUSION: The results indicate a possible link of the studied proteins with BD pathogenesis. Further study of these proteins may contribute to the development of new therapeutic and diagnostic techniques.

[Approaches to vaccine prevention in multiple sclerosis]. / Vaktsinoprofilaktika pri rasseyannom skleroze.

The article presents an overview of modern approaches to vaccine prevention in multiple sclerosis (MS). Compared with the general population, patients with MS have been shown to have an increased risk of morbidity, a tendency to have a more severe course, and a greater mortality from vaccine-preventable infections. At the same time, in Russia, until recently, traditionally adhered to a conservative tactic of limiting vaccination in patients with autoimmune diseases, including MS. The use of various disease-modifying therapies (DMT) may also affect the susceptibility to infections and the severity of their course. Screening for latent infections, determination of immune status, collection of history of past infections and development of a vaccination plan based on these data are an important part of the preparation before the appointment of DMT to control the occurrence or reactivation of infections. The use of inactivated, subunit, conjugate, and toxoid-based vaccines are preferable for MS patients. When developing a vaccination plan, avoid live-attenuated vaccines whenever possible. There are no restrictions on vaccination during first line DMT intake. In case of vaccination in MS patients while using immunosuppressants, including drugs for immune reconstitution therapy, an individual risk assessment and timing are required. The available data on the awareness of patients about vaccine prophylaxis are significantly limited and require mass information events.

[Anhedonia as target symptom in personalized therapy of patients with mood disorders and alcohol use disorder comorbidity]. / Angedoniya kak tselevoi simptom personalizirovannoi antidepressivnoi psikhofarmakoterapii u patsientov s komorbidnymi affektivnymi rasstroistvami i alkogol'noi zavisimost'yu.

OBJECTIVE: To estimate the efficacy of antidepressants in the treatment of anhedonia in mood disorders (MD) comorbid with alcohol use disorder (AUD), considering melatonin concentration in the patient's blood serum. MATERIAL AND METHODS: Seventy patients, aged 18-65 years old, with MD, including patients with- (group F3+F10, n=36) or without comorbid AUD (group F3, n=34), were examined. Control group consisted of 26 healthy volunteers. Clinical-dynamic evaluation was carried out using SIGH-SAD and SHAPS-C. Melatonin concentration was measured with MAGPIX analyzer (Luminex, USA). The statistical analysis was carried out using the SPSS (V. 23.0) standard package. RESULTS: In the case of MD/AUD comorbidity anhedonia symptom does not respond well to psychopharmacotherapy during four weeks (p=0.192, Wilcoxon test) whereas anhedonia in «pure¼ MD does (p=0.007, Wilcoxon test). At the same time, only patients with «pure¼ MD have a statistically significant decrease in melatonin concentration in blood serum compared with the control group (p=0.025, p=0.031, Mann-Whitney test), on the contrary, in the case of MD/AUD comorbidity, a relative increase in melatonin concentration (p>0.05 Mann-Whitney test) was demonstrated. CONCLUSION: The relatively low response of anhedonia symptom in the case of MD/AUD comorbidity compared with the «pure¼ MD, makes perspective using antidepressants with prodophaminergic mechanism of action in this cohort of patients. Furthermore, in MD/AUD comorbidity, contrary to «pure¼ MD, a relative increase in melatonin concentration in blood serum was detected, therefore it could be a limitation to prescribing antidepressants directly or indirectly modulating melatoninergic system.

Antimicrobial and antioxidant activity of Panax ginseng and Hedysarum neglectum root crop extracts.

In order to ensure the timely and uninterrupted supply of medicinal plant raw materials, the methods of cultivation of plant cell cultures, namely, the production of plant root cultures, are relevant. In this paper, the geroprotective potential of Hedysarum neglectum Ledeb and Panax ginseng C. A. Mey root cultures is studied. They were cultured under in vitro conditions by transforming the rhizome (H. neglectum) and seed seedlings (P. ginseng) with Agrobacterium rhizogenes 15834 Swiss. To identify the geroprotective potential, the antimicrobial disc-diffusion method and the antioxidant activity were analyzed by titration of KMnO4 extracts of plant root cultures. The qualitative and quantitative composition was analyzed using high-performance liquid chromatography, thin-layer chromatography, and gas chromatography with mass spectrometry. In the course of the work, the presence of antimicrobial and antioxidant activity of plant root culture extracts was established. Biologically active substances contained in extracts of Hedysarum neglectum Ledeb root crops and Panax ginseng C. A. Mey are characterized by geroprotective potential, so they can act as a source of natural antioxidants in the functional nutrition of the geroprotective orientation.

[Current methods for predicting therapeutic response in patients with depressive disorders]. / Sovremennye metody prognoza terapevticheskogo otveta u patsientov s depressivnymi rasstroistvami.

Depressive disorder is the most common mental illness, which is also one of the leading causes of disability worldwide. In addition, most suicides are associated with depression. Despite all modern achievements in the treatment of depressive disorders, up to 60% of patients did not adequately respond to psychopharmacotherapy (non-responders). Current guidelines and studies characterize non-responders as patients who have an inadequate response to taking two or more antidepressants from different classes within 4 weeks. However, in some cases, such a long wait for a therapeutic response can lead to adverse consequences. Thus, there is a need to develop prognostic methods of therapeutic resistance in patients with depressive disorders. The purpose of this review is to summarize current methods used to predict therapeutic response in patients with depressive disorders. A literature search was conducted using the search terms «depression¼, «antidepressant¼, «outcome¼, «predictor¼, «(bio) marker¼, «treatment-resistant depression¼ and «chronic depression¼. The search was conducted in the PubMed, Scopus, and Google Scholar databases for the time period from 2005 to 2020.

[Executive functions and their role in predicting therapeutic response in patients with depressive disorders]. / Upravlyayushchie kognitivnye funktsii i ikh rol' v prognozirovanii terapevticheskogo otveta u patsientov s depressivnymi rasstroistvami.

OBJECTIVE: To identify differences in executive functions in patients with depressive disorders depending on their sensitivity to antidepressants. MATERIAL AND METHODS: The study included 70 patients with depressive disorder. All patients received syndrome-induced psychopharmacotherapy, which included antidepressants and normotimics. The severity of depressive disorder was assessed using the Hamilton Depression Rating Scale (HDRS). The criterion for the effectiveness of therapy (sensitivity) was an improvement in clinical symptoms by 50% or more, as measured with HDRS. The study was performed in two stages (points): at the first point, patients were examined upon admission to the Department before taking medications, and the second point was performed after a 4-week treatment of patients in the hospital. The assessment of executive functions was performed using computer tests Go/Nogo, Corsi and Stroop. RESULTS AND CONCLUSION: Patients with depressive disorders who were not sensitive to therapy were characterized by low performance in executive functions compared to patients with a positive therapeutic response. Based on the data obtained, a multiple linear regression equation was constructed to predict the therapeutic response based on individual differences in the results of cognitive tests, regardless of potential clinical and demographic factors.

[Clinical and electrophysiological parameters of alcohol dependence and its comorbidity with affective disorders]. / Klinicheskie i neirofiziologicheskie osobennosti pri alkogol'noi zavisimosti i pri ee komorbidnosti s affektivnymi rasstroistvami.

OBJECTIVE: To identify characteristics of and possible differences in clinical and electroencephalographic parameters in patients with alcohol dependence with- and without comorbid affective disorders. MATERIALS AND METHODS: Ninety-five patients, including 74 with an established diagnosis of alcohol dependence and 21 with alcohol dependence and affective disorders, were examined. Duration of alcohol dependence and affective disorder (years), number of hospitalizations and suicidal attempts were analyzed as anamnestic data. Hamilton's anxiety and depression scale (HDRS), the Alcohol Use Disorders Identification Test (AUDIT), the General clinical impression scale (CGI-s) were used as psychometric tools. The study of bioelectric activity of the brain was carried out using a 16-channel encephalograph. The background electroencephalogram was recorded, the values of absolute spectral power and coherence of theta, alpha and beta rhythms were analyzed. RESULTS AND CONCLUSION: Patients with comorbidity of alcohol dependence and affective disorders have a significantly higher risk of suicidal behavior, a greater frequency of hospitalizations, higher levels of anxiety compared with patients without affective disorders. Electrophysiological data have shown that patients with comorbidity of alcohol dependence and affective disorders have higher values of spectral power of alpha-rhythm in all parts of the cerebral cortex (except for temporal lobes) and beta-rhythm in the occipital cortex, as well as an increase in interhemispheric coherence in all frequency ranges.

[A new look at the genetics of neurocognitive deficits in schizophrenia]. / Novyi vzglyad na genetiku neirokognitivnogo defitsita pri shizofrenii.

The article presents current literature data on genetic studies of neurocognitive deficit in schizophrenia, including the genes of neurotransmitter systems (dopaminergic, glutamatergic, and serotonergic); genes analyzed in genome-wide association studies (GWAS), as well as other genetic factors related to the pathophysiological mechanisms underlying schizophrenia and neurocognitive disorders.