[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.

[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.

[Mild encephalopathy with a reversible splenial lesion in a child]. / Sindrom umerennoi entsefalopatii s obratimym porazheniem valika mozolistogo tela u rebenka.

Mild encephalopathy with a reversible splenial lesion (MERS) is a clinical and radiological syndrome that can be caused by infectious and non-infectious factors. The most common neurological symptoms are impaired consciousness, impaired speech, convulsions, muscle weakness, ophthalmoplegia, facial paralysis, and headache. A case of a 5-year-old child with a leading clinical symptom of bilateral transient blindness and radiological characteristics of MERS syndrome is presented.

[Evaluation of the effectiveness of treatment of patients with nonspecific pain syndrome in the lower back with celecoxib and a combined preparation of B vitamins]. / Otsenka effektivnosti lecheniya patsientov s nespetsificheskim bolevym sindromom v poyasnitse tselekoksibom i kombinirovannym preparatom vitaminov gruppy B.

OBJECTIVE: To evaluate the effectiveness of the effect of celecoxib and the combined vitamin complex of group B in comparison with meloxicam in patients with acute and chronic nonspecific lumbar pain (LP). MATERIAL AND METHODS: The effectiveness of the effect on acute (44%; acute pain syndrome (APS)) and chronic (56%; chronic pain syndrome (CPS)) LP of moderate intensity (according to VAS/MPQ) (APS 5.7±2.3/2.13±0.67 points; CPS 5.2±2.8/1.47±0.61 points), the leading component of which is sensory sensations (when APS is lower than in CBS; Kr-W=6.15, p=0.04) and affective disorders in CPS (U=117.5, p=0.04) celecoxib without (APS 25%; CPS 75%) and with the addition of Neuromultivit (APS 36%; CPS 64%) and in comparison with meloxicam (APS 100%) against the background of basic therapy in 93 patients (61.3% women and 38.7% men; average age 49.9±9. years) with nonspecific LP pain syndrome in the lower back, with a low degree of severity of motor function (MF) disorders according to the ICF (2±1 points), due to spondyloarthrosis of the lumbosacral spine. RESULTS: It was found that celecoxib and meloxicam cause the same significant remitting decrease in the severity of APS and restoration of MF disorders in patients with APS, equally cause rare adverse events (gastropathy, increased blood pressure) in comorbid pathology. Celecoxib proved to be more effective in relieving CPS and improving MF (p<0.05), and the combination of celecoxib with Neuromultivit caused more pronounced relief of APS and CPS, restoration of MF (p<0.01). A steady decrease in the intensity of PS (1-2 points according to VAS), recovery of MF occurs only on the 10th-11th day of therapy (p<0.01), with complete relief of LP by day 21 only in 60.22% of cases. CONCLUSION: The results of the study confirm the benefits of celecoxib in combination with a vitamin complex for the relief of CPS.

[The role of alleles with an intermediate number of trinucleotide repeats in Parkinson's disease and other neurodegenerative disorders]. / Rol' allelei s promezhutochnym kolichestvom trinukleotidnykh povtorov pri bolezni Parkinsona i drugikh neirodegenerativnykh zabolevaniyakh.

Genetic factors underlie the pathological processes that cause the manifestation of a wide range of neurodegenerative diseases. The pathological expansion of unstable trinucleotide repeats is known to lead monogenic neurological diseases such as Huntington's disease, Kennedy's disease, spinocerebellar ataxia, and others. However, the latest data suggests individuals with intermediate allele (IA) repeat length have a risk of developing common neurological phenotype, for example, Parkinson's disease, Alzheimer's disease. In this study, we review the current knowledge on intermediate alleles of HTT gene for pathogenesis and clinical features of neurodegenerative diseases, with the focus on Parkinson's disease. Early diagnosis of neurodegenerative disease and genetic counselling of the family can be improved via the implementation of specific management strategies of IA carriers by team of highly experienced professionals in the fields of neurology and genetics.

High temperature superradiant phase transition in quantum structures with a complex network interface.

In the present work we propose a novel, to the best of our knowledge, quantum material concept, which enables superstrong and/or ultrastrong interaction of two-level systems with the photonic field in a complex network. Within the mean field approximation we examine phase transition to superradiance that results in two excitation (polariton) branches and is accompanied by the appearance of non-zero macroscopic polarization of two-level systems. We characterize the statistical properties of networks by the first, 〈k〉, and second normalized, ζ ≡ 〈k2〉/〈k〉, moments for node degree distribution. We have shown that the Rabi frequency is essentially enhanced due to the topology of the network within the anomalous domain where 〈k〉 and ζ sufficiently grow. The multichannel (multimode) structure of matter-field interaction leads superstrong coupling that provides primary behavior of the high temperature phase transition. The results obtained pave the way for the design of new photonic and polaritonic circuits, quantum networks for efficient processing quantum information at high (room) temperatures.

Preeclampsia: inflammatory signature of decidual cells in early manifestation of disease.

INTRODUCTION: Preeclampsia is a pregnancy-specific complication characterized by hypertension in combination with proteinuria and/or various manifestations of multiple organ failure. It is believed that etiology of preeclampsia lies in dysfunction of the placenta and disorder of the maternal-fetal interactions. In preeclampsia decidual membrane, the maternal part of the placenta which normally supports immunological tolerance of the maternal organism to the semi-allogeneic fetus, becomes a site of inflammation. METHODS: The aim of our study was to characterize the phenotype of decidual macrophages and plasma profiles in patients with late- and early-onset preeclampsia as compared with controls (n = 43). Decidual cells were obtained by enzymatic digestion method and characterized by flow cytometry analysis, real-time PCR, bioinformatics analysis, immunohistochemistry, and Western blot. Plasma samples were analyzed by multiplex assay. RESULTS: The number of inflammation-associated CD86+ and CX3CR1+ cells was significantly higher in the early-onset preeclampsia while the portion of CD163+ cells was significantly higher among studied groups. We observed significant increase of endothelin-1 gene expression and a significant decrease in eNOS and GNB3 expression and TGFß relative protein level in decidual cells of the early-onset preeclampsia samples. We also revealed elevation of pro- and anti-inflammatory cytokines in plasma of preeclampsia groups. DISCUSSION: Our findings reflect profound early-onset preeclampsia-associated alterations in the decidua and emphasize the importance of the decidua as a link in the development of preeclampsia.

Expression of Metalloproteinases and Type I and III Collagens during Healing of Excisional Skin Wound on the Abdomen and Back in Rats.

The study was carried out using a novel rat model developed in our laboratory, namely16 mm diameter circular excisional wounds were generated on the abdomen which resulted in minimal scarring. Restoration of the skin integrity was completed by day 60 after the wounding surgery. By this time, regenerates on the abdomen were stronger than on the back (at, respectively, 58 and 17.4 % of the tensile strength of the intact skin at corresponding location) and the ratio of type I and type III collagens in regenerates on the abdomen reached the level of intact skin at the same location. On days 3 to 14, the ratio of Mmp9/Timp1 expression levels on the abdomen was higher than on the back. On days 20 and 30, the Mmp9/Timp1 ratio on the abdomen was identical to the level of intact skin, whereas the increased MMPs expression levels on the back were maintained until day 30. It has been shown for the first time that according to functional and molecular characteristics, wound healing on the abdomen of an adult rat is more similar to complete regeneration than scarring repair of the back skin.

Analysis of the Expression of Regulator Genes in Kupffer Cells and Monocytes.

Differences in the gene expression profiles in resident macrophages (in particular, Kupffer cells) and monocytes were revealed. However, these differences in gene expression profiles do not allow considering resident liver macrophages as purely M2 macrophages and monocytes as purely M1 macrophages. At the same time, a significant number of the genes upregulated in Kupffer cells are associated with normal regulation of liver functions (Arg 1, Flt, iNOs, and Kng). In monocytes, the expression of genes Alox15, Alox12, Tlr2, Tlr4, Tlr7, and Tlr8 (typical functional genes of macrophages) was also upregulated in comparison with Kupffer cells.

Analysis of Gut Microbiota in Patients with Parkinson's Disease.

Gut microbiota of patients with Parkinson's disease and healthy volunteers was analyzed by the method of high throughput 16S rRNA sequencing of bacterial genomes. In patients with Parkinson's diseases, changes in the content of 9 genera and 15 species of microorganisms were revealed: reduced content of Dorea, Bacteroides, Prevotella, Faecalibacterium, Bacteroides massiliensis, Stoquefichus massiliensis, Bacteroides coprocola, Blautia glucerasea, Dorea longicatena, Bacteroides dorei, Bacteroides plebeus, Prevotella copri, Coprococcus eutactus, and Ruminococcus callidus, and increased content of Christensenella, Catabacter, Lactobacillus, Oscillospira, Bifidobacterium, Christensenella minuta, Catabacter hongkongensis, Lactobacillus mucosae, Ruminococcus bromii, and Papillibacter cinnamivorans. This microbiological pattern of gut microflora can trigger local inflammation followed by aggregation of α-synuclein and generation of Lewy bodies.

[A role of the gastrointestinal tract microbiota in the pathogenesis of Parkinson's disease]. / Vozmozhnaia rol' mikrobioty zheludochno-kishechnogotraktavpatogenezebolezniarkinsona.

Microbiota is a community of microorganisms, viruses, protozoa, colonizing the gut. There are tight phylogenetic relationships between the gut microbiota and the human body, the disturbance of which may lead to the CNS dysfunction as well as to the development of neurodegenerative diseases. This review focuses on general and specific aspects of the influence of gut microbiota on the pathogenesis of Parkinson's disease (PD). Current theories and models of the relationship between microbiota and brain structures in PD are presented with a specific focus on neurochemical and immunological aspects of the problem.

[Correlation Between Emotional-Affective Disorders and Gut Microbiota Composition in Patients with Parkinson's Disease].

Background: Despite the efforts of scientific community the data available on the correlation between emotional-affective symptoms of Parkinson's disease and changes in microbiome is still scarce. Deeper studies of nonmotor symptoms evident in premotor stages of the disease and the reciprocal influence of microbiota may help to understand the etiology and pathogenesis of PD neurodegeneration better. Aim of the Study: Discover the relations between emotional-affective disorders prevalent in PD population and changes in gut microbiota composition. Methods: 51 patient diagnosed with PD participated in the study. Every participant's emotional-affective state was examined using Beck's Depression Inventory (BDI) and Hospital Anxiety and Depression Scale (HADS). Taxonomic richness of microbiome was studied using 16S ribosomal RNA gene sequencing, bioinformatics, and statistical analysis. Results: Anxiety and depression are prevalent affective disorders in patients with PD. In our study, most of the subjects demonstrated certain anxiety and depression. Taxonomic diversity of gut microbiota in BP was increasing with the increase in anxiety levels, reaching the maximum in the group with subclinical anxiety, and decreasing in the group with clinically significant anxiety disorder. At the species level, patients with clinically significant anxiety had higher abundance of Clostridium clariflavum compared to the anxiety-free patients. Patients with moderate depression were characterized by the higher prevalence of Christensenella minuta, Clostridium disporicum, and Oscillibacter valericigenes compared to subjects without depression or with mild depression. Conclusion: The data we received in our study allow better understanding of PD pathogenesis.

[Clinical experience of the use of agomelatine in the treatment of patients with depression and chronic brain ischemia].

OBJECTIVE: To study the efficacy and tolerability of agomelatine (valdoxan) in treatment of mild depressive states in patients with chronic brain ischemia (CBI). MATERIAL AND METHODS: The study comprised 33 patients (23 women, 10 men, average age 54.5 years), including 12 people (36.4%) with CBI, stage I, and 21 (63.6%) with CBI, stage II. All patients had a single depressive episode of mild severity. Diagnosis of affective and cognitive impairment was carried out using clinical and neuropsychological methods (the Hamilton Depression Rating Scale (HDRS-17), the Hospital Anxiety and Depression Scale (HADS), the night sleep questionnaire developed by A.M. Vein, the Mini-mental state examination (MMSE), the modified Mini-Cog method, the Montreal Cognitive Assessment Scale (MoCA), the Clinical Global Impression scale (CGI-S, CGI-I) to assess the degree and dynamics of the disease, the Patient Global Impression (PGI) scale. The survey had been performed after 2,4 and 8 weeks of treatment. Agomelatine (valdoxan) was used 1 time per day in the evening in a dose of 25 mg (1 tablet). RESULTS AND CONCLUSION: Agomelatine improved sleep from the second week of treatment, reduced anxiety symptoms after six weeks and depressive symptoms after eight weeks. The improvement of cognitive functions was noted as well. No side-effects was observed. The results revealed the high antidepressive activity of the drug in treatment of mild depressive states in patients with chronic brain ischemia, the balanced spectrum of effects on anxiety, depression, insomnia, the positive effect on cognitive functions that allows to recommend agomelatine in treatment of patients with CBI.

[Methods for evaluating of olfactory function in patients with Parkinson's disease]. / Analiz metodov otsenki obonianiia u patsientov s bolezn'iu Parkinsona.

Olfactory disorder takes a special place among non-motor symptoms of Parkinson's disease (PD) as one of earliest signs of the disease. Based on literature data, authors suggest that simple and structured tests for detection of olfactory disorders should be part of diagnostic algorithm for early detection of PD) and occupy a special place in differential diagnosis of diseases of the extrapyramidal system. Literature on the methods of study of olfactory function recommended as an additional instrument for PD diagnosis is presented.

Pseudo-ε expansion and renormalized coupling constants at criticality.

Universal values of dimensional effective coupling constants g(2k) that determine nonlinear susceptibilities χ(2k) and enter the scaling equation of state are calculated for n-vector field theory within the pseudo-ε expansion approach. Pseudo-ε expansions for g(6) and g(8) at criticality are derived for arbitrary n. Analogous series for ratios R(6) = g(6)/g(4)(2) and R(8) = g(8)/g(4)(3) that figure in the equation of state are also found, and the pseudo-ε expansion for Wilson fixed point location g(4)(*) descending from the six-loop renormalization group (RG) expansion for the ß function is reported. Numerical results are presented for 0 ≤ n ≤ 64, with the most attention paid to the physically important cases n = 0,1,2,3. Pseudo-ε expansions for quartic and sextic couplings have rapidly diminishing coefficients, so Padé resummation turns out to be sufficient to yield high-precision numerical estimates. Moreover, direct summation of these series with optimal truncation gives values of g(4)(*) and R(6)(*) that are almost as accurate as those provided by the Padé technique. Pseudo-ε expansion estimates for g(8)(*) and R(8)(*) are found to be much worse than those for lower-order couplings independently of the resummation method employed. The numerical effectiveness of the pseudo-ε expansion approach in two dimensions is also studied. Pseudo-ε expansion for g(4)(*) originating from the five-loop RG series for the ß function of two-dimensional λϕ(4) field theory is used to get numerical estimates for n ranging from 0 to 64. The approach discussed gives accurate enough values of g(4)(*) down to n = 2 and leads to fair estimates for Ising and polymer (n = 0) models.

Fisher exponent from pseudo-ε expansion.

The critical exponent η for three-dimensional systems with an n-vector order parameter is evaluated in the framework of the pseudo-ε expansion approach. The pseudo-ε expansion (τ series) for η found up to the τ(7) term for n = 0, 1, 2, 3 and within the τ(6) order for general n is shown to have a structure that is rather favorable for getting numerical estimates. The use of Padé approximants and direct summation of the τ series result in iteration procedures rapidly converging to the asymptotic values that are very close to the most reliable numerical estimates of η known today. The origin of such an efficiency is discussed and shown to lie in the general properties of the pseudo-ε expansion machinery interfering with some peculiarities of the renormalization group expansion of η.

Critical exponents in two dimensions and pseudo-ε expansion.

The critical behavior of two-dimensional n-vector λϕ4 field model is studied within the framework of pseudo-ε expansion approach. Pseudo-ε expansions for Wilson fixed-point location g* and critical exponents originating from five-loop two-dimensional renormalization-group series are derived. Numerical estimates obtained within Padé and Padé-Borel resummation procedures as well as by direct summation are presented for n=1, n=0, and n=-1, i.e., for the models which are exactly solvable. The pseudo-ε expansions for g*, critical exponents γ, and ν have small lower-order coefficients and slow increasing higher-order ones. As a result, direct summation of these series with optimal cutoff provides numerical estimates that are no worse than those given by the resummation approaches mentioned. This enables one to consider the pseudo-ε expansion technique itself as some specific resummation method.

Epidemiological, clinical and viral determinants of the increased prevalence of high-risk human papillomavirus (HPV) infections in elderly women.

BACKGROUND: Population-based studies have reported a second peak of human papillomavirus (HPV) prevalence among women > 55 years, but reasons for this U-shaped HPV prevalence curve are poorly understood. OBJECTIVES: To analyse determinants of high-risk HPV (HR-HPV) infections among postmenopausal women. STUDY DESIGN AND METHODS: A cohort of 3,187 women was stratified into three age categories: i) youngest age group < 25 years (n = 1.103); ii) women between 26-55 years (n = 2.004), and iii) women > 55 years (n = 80), analysed for epidemiological, clinical and virological determinants of their HR-HPV infections. Real-time PCR was used for HPV genotyping, analysis of viral loads for HPV16, 18/45, 31, 33/52/58, 35 and 39, and load of integrated HPV16. RESULTS: Age-standardised prevalence of HR-HPV infections showed a second peak among women > 55 years, with a perfect U-shaped curve (R2 = 0.966). The factors explaining this increased HR-HPV prevalence among older women include: i) cohort effect, ii) higher viral loads for HR-HPV types with cubic model curve (R2 = 0.714) for HPV 16, iii) distinct shift (p = 0.0001) from multiple-type infections to single HR-HPV types, iv) transition from episomal to integrated HPV16 (p = 0.009), v) higher load of integrated HPV16 (p = 0.009), and, vi) higher proportion of incident infections, higher rate of viral persistence, and lower rate of HR-HPV clearance. CONCLUSIONS: These data suggest that in women who fail to eradicate their HR-HPV infection until menopause, selection of integrated viral clone has taken place, driving the process towards progressing disease. Consequent to this, most of the HR-HPV infections in women > 55 years were associated with high-grade CIN or invasive carcinoma.

Factors predicting persistence of high-risk human papillomavirus (HPV) infections in women prospectively followed-up in three New Independent States (NIS) of the former Soviet Union.

BACKGROUND: We completed an analysis of the factors predicting the persistence of high risk (HR) HPV infections in women participating in a multicenter screening trial in three NIS countries. METHODS: The 543 baseline HR HPV-positive women included in this analysis are derived from a sub-cohort of 887 women who were prospectively followed-up for a mean of 21.6 months (range: 0.5-42.9) as a part of a multi-center screening study in three NIS countries (the NIS cohort study; n = 3,187 women). Of these 543 women, 273 showed persistent HR-HPV in serial Hybrid Capture II (HCII) testing during the follow-up (Group 1), whereas 270 women cleared their infection (Group 2). These two groups were compared with their epidemiological, clinical, and virological data (HCII, PCR) to disclose the factors predicting persistent HR-HPV infection. RESULTS: Women with persistent HR-HPV infections were significantly younger (27.3 yrs) than those who cleared their infection (29.1 yrs) (p = 0.006), and their follow-up time was shorter; 14.1 and 21 months, respectively (p = 0.0001). Both variables were treated as confounders in the multivariate analyses. Of the 66 recorded epidemiological variables, only being a current smoker proved to be an independent predictor (OR 1.693; 95% CI 1.114-2.573; p=0.014). Baseline colposcopy, biopsy or Pap smear did not predict HPV persistence, whereas an incident or persistent abnormal Pap during the follow-up were independent predictors in a multivariate model (p = 0.005), together with the high viral load (HCII RLU/CO at 100 pg/ml cut-off), and HR HPV positive PCR test (p = 0.0001). When all significant variables were entered in the regression model, only the follow-up time (OR 0.950, 95% CI 0.924-0.976; p = 0.0001) and HR-HPV positive PCR (OR 4.169, 95% CI 1.741-9.987; p = 0.001), remained independent predictors. CONCLUSIONS: While several factors were related to HR-HPV persistence in univariate analysis and when adjusted for age and follow-up time as confounders, the only independent predictors in the multivariate regression model were follow-up time and HR-HPV positive PCR. Clearly more data are needed on type-specific persistence and HPV integration as its predictors.