High-Tech Methods of Cytokine Imbalance Correction in Intervertebral Disc Degeneration.

An important mechanism for the development of intervertebral disc degeneration (IDD) is an imbalance between anti-inflammatory and pro-inflammatory cytokines. Therapeutic and non-therapeutic approaches for cytokine imbalance correction in IDD either do not give the expected result, or give a short period of time. This explains the relevance of high-tech medical care, which is part of specialized care and includes the use of new resource-intensive methods of treatment with proven effectiveness. The aim of the review is to update knowledge about new high-tech methods based on cytokine imbalance correction in IDD. It demonstrates promise of new approaches to IDD management in patients resistant to previously used therapies, including: cell therapy (stem cell implantation, implantation of autologous cultured cells, and tissue engineering); genetic technologies (gene modifications, microRNA, and molecular inducers of IDD); technologies for influencing the inflammatory cascade in intervertebral discs mediated by abnormal activation of inflammasomes; senolytics; exosomal therapy; and other factors (hypoxia-induced factors; lysyl oxidase; corticostatin; etc.).

Efficiency of Direct Transcutaneous Electroneurostimulation of the Median Nerve in the Regression of Residual Neurological Symptoms after Carpal Tunnel Decompression Surgery.

Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy. CTS therapy includes wrist immobilization, kinesiotherapy, non-steroidal anti-inflammatory drugs, carpal tunnel steroid injection, acupuncture, and physical therapy. Carpal tunnel decompression surgery (CTDS) is recommended after failure of conservative therapy. In many cases, neurological disorders continue despite CTDS. The aim of this study was to investigate the efficiency of direct transcutaneous electroneurostimulation (TENS) of the median nerve in the regression of residual neurological symptoms after CTDS. Material and Methods: 60 patients aged 28-62 years with persisting sensory and motor disorders after CTDS were studied; 15 patients received sham stimulation with a duration 30 min.; 15 patients received high-frequency low-amplitude TENS (HF TENS) with a duration 30 min; 15 patients received low-frequency high-amplitude TENS (LF TENS) with a duration 30 min; and 15 patients received a co-administration of HF TENS (with a duration of15 min) and LF TENS (with a duration of 15 min). Results: Our research showed that TENS significantly decreased the pain syndrome, sensory disorders, and motor deficits in the patients after CTDS. Predominantly, negative and positive sensory symptoms and the pain syndrome improved after the HF TENS course. Motor deficits, reduction of fine motor skill performance, electromyography changes, and affective responses to chronic pain syndrome regressed significantly after the LF TENS course. Co-administration of HF TENS and LF TENS was significantly more effective than use of sham stimulation, HF TENS, or LF TENS in patients with residual neurological symptoms after CTDS.

Association of the ACTN3 Gene's Single-Nucleotide Variant Rs1815739 (R577X) with Sports Qualification and Competitive Distance in Caucasian Athletes of the Southern Urals.

An elite athlete's status is associated with a multifactorial phenotype depending on many environmental and genetic factors. Of course, the peculiarities of the structure and function of skeletal muscles are among the most important characteristics in the context of athletic performance. PURPOSE: To study the associations of SNV rs1815739 (C577T or R577X) allelic variants and genotypes of the ACTN3 gene with qualification and competitive distance in Caucasian athletes of the Southern Urals. METHODS: A total of 126 people of European origin who lived in the Southern Urals region took part in this study. The first group included 76 cyclical sports athletes (speed skating, running disciplines in track-and-field): SD (short distances) subgroup-40 sprinters (mean 22.1 ± 2.4 y.o.); LD (long distances) subgroup-36 stayer athletes (mean 22.6 ± 2.7 y.o.). The control group consisted of 50 healthy nonathletes (mean 21.4 ± 2.7 y.o.). We used the Step One Real-Time PCR System (Applied Biosystems, USA) device for real-time polymerase chain reaction. RESULTS: The frequency of the major allele R was significantly higher in the SD subgroup compared to the control subgroup (80% vs. 64%; p-value = 0.04). However, we did not find any significant differences in the frequency of the R allele between the athletes of the SD subgroup and the LD subgroup (80% vs. 59.7%, respectively; p-value > 0.05). The frequency of the X allele was lower in the SD subgroup compared to the LD subgroup (20% vs. 40.3%; p-value = 0.03). The frequency of homozygous genotype RR was higher in the SD subgroup compared to the control group (60.0% vs. 34%; p-value = 0.04). The R allele was associated with competitive distance in the SD group athletes compared to those of the control group (OR = 2.45 (95% CI: 1.02-5.87)). The X allele was associated with competitive distance in the LD subgroup compared to the SD subgroup (OR = 2.7 (95% CI: 1.09-6.68)). CONCLUSIONS: Multiplicative and additive inheritance models demonstrated that high athletic performance for sprinters was associated with the homozygous dominant genotype 577RR in cyclical sports athletes of Caucasian origin in the Southern Urals.

Molecular Basic of Pharmacotherapy of Cytokine Imbalance as a Component of Intervertebral Disc Degeneration Treatment.

Intervertebral disc degeneration (IDD) and associated conditions are an important problem in modern medicine. The onset of IDD may be in childhood and adolescence in patients with a genetic predisposition. With age, IDD progresses, leading to spondylosis, spondylarthrosis, herniated disc, spinal canal stenosis. One of the leading mechanisms in the development of IDD and chronic back pain is an imbalance between pro-inflammatory and anti-inflammatory cytokines. However, classical therapeutic strategies for correcting cytokine imbalance in IDD do not give the expected response in more than half of the cases. The purpose of this review is to update knowledge about new and promising therapeutic strategies based on the correction of the molecular mechanisms of cytokine imbalance in patients with IDD. This review demonstrates that knowledge of the molecular mechanisms of the imbalance between pro-inflammatory and anti-inflammatory cytokines may be a new key to finding more effective drugs for the treatment of IDD in the setting of acute and chronic inflammation.

Valproate-Induced Metabolic Syndrome.

Valproic acid (VPA) and its salts (sodium calcium magnesium and orotic) are psychotropic drugs that are widely used in neurology and psychiatry. The long-term use of VPA increases the risk of developing adverse drug reactions (ADRs), among which metabolic syndrome (MetS) plays a special role. MetS belongs to a cluster of metabolic conditions such as abdominal obesity, high blood pressure, high blood glucose, high serum triglycerides, and low serum high-density lipoprotein. Valproate-induced MetS (VPA-MetS) is a common ADR that needs an updated multidisciplinary approach to its prevention and diagnosis. In this review, we consider the results of studies of blood (serum and plasma) and the urinary biomarkers of VPA-MetS. These metabolic biomarkers may provide the key to the development of a new multidisciplinary personalized strategy for the prevention and diagnosis of VPA-MetS in patients with neurological diseases, psychiatric disorders, and addiction diseases.

Genetic Predictors of Antipsychotic Efflux Impairment via Blood-Brain Barrier: Role of Transport Proteins.

Antipsychotic (AP)-induced adverse drug reactions (ADRs) are a current problem of biological and clinical psychiatry. Despite the development of new generations of APs, the problem of AP-induced ADRs has not been solved and continues to be actively studied. One of the important mechanisms for the development of AP-induced ADRs is a genetically-determined impairment of AP efflux across the blood-brain barrier (BBB). We present a narrative review of publications in databases (PubMed, Springer, Scopus, Web of Science E-Library) and online resources: The Human Protein Atlas; GeneCards: The Human Gene Database; US National Library of Medicine; SNPedia; OMIM Online Mendelian Inheritance in Man; The PharmGKB. The role of 15 transport proteins involved in the efflux of drugs and other xenobiotics across cell membranes (P-gp, TAP1, TAP2, MDR3, BSEP, MRP1, MRP2, MRP3, MRP4, MRP5, MRP6, MRP7, MRP8, MRP9, BCRP) was analyzed. The important role of three transporter proteins (P-gp, BCRP, MRP1) in the efflux of APs through the BBB was shown, as well as the association of the functional activity and expression of these transport proteins with low-functional and non-functional single nucleotide variants (SNVs)/polymorphisms of the ABCB1, ABCG2, ABCC1 genes, encoding these transport proteins, respectively, in patients with schizophrenia spectrum disorders (SSDs). The authors propose a new pharmacogenetic panel "Transporter protein (PT)-Antipsychotic (AP) Pharmacogenetic test (PGx)" (PTAP-PGx), which allows the evaluation of the cumulative contribution of the studied genetic biomarkers of the impairment of AP efflux through the BBB. The authors also propose a riskometer for PTAP-PGx and a decision-making algorithm for psychiatrists. Conclusions: Understanding the role of the transportation of impaired APs across the BBB and the use of genetic biomarkers for its disruption may make it possible to reduce the frequency and severity of AP-induced ADRs, since this risk can be partially modified by the personalized selection of APs and their dosing rates, taking into account the genetic predisposition of the patient with SSD.

Amyotrophic Lateral Sclerosis Mimic Syndrome in a 24-Year-Old Man with Chiari 1 Malformation and Syringomyelia: A Clinical Case.

Chiari 1 Malformation (CM1) is classically defined as a caudal displacement of the cerebellar tonsils through the foramen magnum into the spinal cord. Modern imaging techniques and experimental studies disclose a different etiology for the development of CM1, but the main etiology factor is a structural defect in the skull as a deformity or partial reduction, which push down the lower part of the brain and cause the cerebellum to compress into the spinal canal. CM1 is classified as a rare disease. CM1 can present with a wide variety of symptoms, also non-specific, with consequent controversies on diagnosis and surgical decision-making, particularly in asymptomatic or minimally symptomatic. Other disorders, such as syringomyelia (Syr), hydrocephalus, and craniocervical instability can be associated at the time of the diagnosis or appear secondarily. Therefore, CM1-related Syr is defined as a single or multiple fluid-filled cavities within the spinal cord and/or the bulb. A rare CM1-related disorder is syndrome of lateral amyotrophic sclerosis (ALS mimic syndrome). We present a unique clinical case of ALS mimic syndrome in a young man with CM1 and a huge singular syringomyelic cyst with a length from segment C2 to Th12. At the same time, the clinical picture showed upper hypotonic-atrophic paraparesis in the absence of motor disorders in the lower extremities. Interestingly, this patient did not have a disorder of superficial and deep types of sensitivity. This made it difficult to diagnose CM1. For a long time, the patient's symptoms were regarded as a manifestation of ALS, as an independent neurological disease, and not as a related disorder of CM1. Surgical treatment for CM1 was not effective, but it allowed to stabilize the course of CM1-related ALS mimic syndrome over the next two years.

Single-Nucleotide Polymorphisms as Biomarkers of Antipsychotic-Induced Akathisia: Systematic Review.

Antipsychotic-induced akathisia (AIA) is a movement disorder characterized by a subjective feeling of inner restlessness or nervousness with an irresistible urge to move, resulting in repetitive movements of the limbs and torso, while taking antipsychotics (APs). In recent years, there have been some associative genetic studies of the predisposition to the development of AIA. Objective: The goal of our study was to review the results of associative genetic and genome-wide studies and to systematize and update the knowledge on the genetic predictors of AIA in patients with schizophrenia (Sch). Methods: We searched full-text publications in PubMed, Web of Science, Springer, Google Scholar, and e-Library databases from 1977 to 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) quality scale was used for the critical selection of the studies. Results: We identified 37 articles, of which 3 were included in the review. Thus, the C allele of rs1800498 (59414 C>T) and the A allele of rs1800497 (17316 G>A) (TaqIA) from the DRD2 gene as well as the TT genotype rs13212041 (77461407 C>T) from the HTR1B gene were found to be associated with AIA. Conclusions: Uncovering the genetic biomarkers of AIA may provide a key to developing a strategy for the personalized prevention and treatment of this adverse neurological drug reaction of APs in patients with Sch in real clinical practice.

Association of Single-Nucleotide Polymorphisms Rs2779249 (chr17:26128581 C>A) and Rs rs2297518 (chr17: chr17:27769571 G>A) of the NOS2 Gene with Tension-Type Headache and Arterial Hypertension Overlap Syndrome in Eastern Siberia.

Inducible nitric oxide (NO) synthase (iNOS), encoded by the NOS2 gene, promotes the generation of high levels of NO to combat harmful environmental influences in a wide range of cells. iNOS can cause adverse effects, such as falling blood pressure, if overexpressed. Thus, according to some data, this enzyme is an important precursor of arterial hypertension (AH) and tension-type headache (TTH), which are the most common multifactorial diseases in adults. The purpose of this study was to investigate the association of rs2779249 (chr17:26128581 C>A) and rs2297518 (chr17: chr17:27769571 G>A) of the NOS2 gene with TTH and AH overlap syndrome (OS) in Caucasians in Eastern Siberia. The sample size was 91 participants: the first group-30 patients with OS; the second group-30 patients AH; and the third group-31 healthy volunteers. RT-PCR was used for the determination of alleles and genotypes of the SNPs rs2779249 and rs2297518 of the NOS2 gene in all groups of participants. We showed that the frequency of allele A was significantly higher among patients with AH compared with healthy volunteers (p-value < 0.05). The frequency of the heterozygous genotype CA of rs2779249 was higher in the first group vs. the control (p-value = 0.03), and in the second group vs. the control (p-value = 0.045). The frequency of the heterozygous genotype GA of rs2297518 was higher in the first group vs. the control (p-value = 0.035), and in the second group vs. the control (p-value = 0.001). The allele A of rs2779249 was associated with OS (OR = 3.17 [95% CI: 1.31-7.67], p-value = 0.009) and AH (OR = 2.94 [95% CI: 1.21-7.15], p-value = 0.015) risks compared with the control. The minor allele A of rs2297518 was associated with OS (OR = 4.0 [95% CI: 0.96-16.61], p-value = 0.035) and AH (OR = 8.17 [95% CI: 2.03-32.79], p-value = 0.001) risks compared with the control. Therefore, our pilot study demonstrated that the SNPs rs2779249 and rs229718 of the NOS2 gene could be promising genetic biomarkers for this OS risk in Caucasians from Eastern Siberia.

Cytokine Imbalance as a Biomarker of Intervertebral Disk Degeneration.

The intervertebral disk degeneration (IDD) and its associated conditions are an important problem in modern medicine. The onset of IDD may be in childhood and adolescence in patients with a genetic predisposition. IDD progresses with age, leading to spondylosis, spondylarthrosis, intervertebral disk herniation, and spinal stenosis. The purpose of this review is an attempt to summarize the data characterizing the patterns of production of pro-inflammatory and anti-inflammatory cytokines in IDD and to appreciate the prognostic value of cytokine imbalance as its biomarker. This narrative review demonstrates that the problem of evaluating the contribution of pro-inflammatory and anti-inflammatory cytokines to the maintenance or alteration of cytokine balance may be a new key to unlocking the mystery of IDD development and new therapeutic strategies for the treatment of IDD in the setting of acute and chronic inflammation. The presented data support the hypothesis that cytokine imbalance is one of the most important biomarkers of IDD.

Therapeutic and Toxic Effects of Valproic Acid Metabolites.

Valproic acid (VPA) and its salts are psychotropic drugs that are widely used in neurological diseases (epilepsy, neuropathic pain, migraine, etc.) and psychiatric disorders (schizophrenia, bipolar affective disorder, addiction diseases, etc.). In addition, the indications for the appointment of valproate have been expanding in recent years in connection with the study of new mechanisms of action of therapeutic and toxic metabolites of VPA in the human body. Thus, VPA is considered a component of disease-modifying therapy for multiple tumors, neurodegenerative diseases (Huntington's disease, Parkinson's disease, Duchenne progressive dystrophy, etc.), and human immunodeficiency syndrome. The metabolism of VPA is complex and continues to be studied. Known pathways of VPA metabolism include: ß-oxidation in the tricarboxylic acid cycle (acetylation); oxidation with the participation of cytochrome P-450 isoenzymes (P-oxidation); and glucuronidation. The complex metabolism of VPA explains the diversity of its active and inactive metabolites, which have therapeutic, neutral, or toxic effects. It is known that some active metabolites of VPA may have a stronger clinical effect than VPA itself. These reasons explain the relevance of this narrative review, which summarizes the results of studies of blood (serum, plasma) and urinary metabolites of VPA from the standpoint of the pharmacogenomics and pharmacometabolomics. In addition, a new personalized approach to assessing the cumulative risk of developing VPA-induced adverse reactions is presented and ways for their correction are proposed depending on the patient's pharmacogenetic profile and the level of therapeutic and toxic VPA metabolites in the human body fluids (blood, urine).

Genetic Biomarkers of Antipsychotic-Induced Prolongation of the QT Interval in Patients with Schizophrenia.

Antipsychotics (AP) induced prolongation of the QT interval in patients with schizophrenia (Sch) is an actual interdisciplinary problem as it increases the risk of sudden death syndrome. Long QT syndrome (LQTS) as a cardiac adverse drug reaction is a multifactorial symptomatic disorder, the development of which is influenced by modifying factors (APs' dose, duration of APs therapy, APs polytherapy, and monotherapy, etc.) and non-modifying factors (genetic predisposition, gender, age, etc.). The genetic predisposition to AP-induced LQTS may be due to several causes, including causal mutations in the genes responsible for monoheme forms of LQTS, single nucleotide variants (SNVs) of the candidate genes encoding voltage-dependent ion channels expressed both in the brain and in the heart, and SNVs of candidate genes encoding key enzymes of APs metabolism. This narrative review summarizes the results of genetic studies on AP-induced LQTS and proposes a new personalized approach to assessing the risk of its development (low, moderate, high). We recommend implementation in protocols of primary diagnosis of AP-induced LQTS and medication dispensary additional observations of the risk category of patients receiving APs, deoxyribonucleic acid profiling, regular electrocardiogram monitoring, and regular therapeutic drug monitoring of the blood APs levels.

The Role of D-Serine and D-Aspartate in the Pathogenesis and Therapy of Treatment-Resistant Schizophrenia.

Schizophrenia (Sch) is a severe and widespread mental disorder. Antipsychotics (APs) of the first and new generations as the first-line treatment of Sch are not effective in about a third of cases and are also unable to treat negative symptoms and cognitive deficits of schizophrenics. This explains the search for new therapeutic strategies for a disease-modifying therapy for treatment-resistant Sch (TRS). Biological compounds are of great interest to researchers and clinicians, among which D-Serine (D-Ser) and D-Aspartate (D-Asp) are among the promising ones. The Sch glutamate theory suggests that neurotransmission dysfunction caused by glutamate N-methyl-D-aspartate receptors (NMDARs) may represent a primary deficiency in this mental disorder and play an important role in the development of TRS. D-Ser and D-Asp are direct NMDAR agonists and may be involved in modulating the functional activity of dopaminergic neurons. This narrative review demonstrates both the biological role of D-Ser and D-Asp in the normal functioning of the central nervous system (CNS) and in the pathogenesis of Sch and TRS. Particular attention is paid to D-Ser and D-Asp as promising components of a nutritive disease-modifying therapy for TRS.

Cytokine Imbalance as a Biomarker of Treatment-Resistant Schizophrenia.

Treatment-resistant schizophrenia (TRS) is an important and unresolved problem in biological and clinical psychiatry. Approximately 30% of cases of schizophrenia (Sch) are TRS, which may be due to the fact that some patients with TRS may suffer from pathogenetically "non-dopamine" Sch, in the development of which neuroinflammation is supposed to play an important role. The purpose of this narrative review is an attempt to summarize the data characterizing the patterns of production of pro-inflammatory and anti-inflammatory cytokines during the development of therapeutic resistance to APs and their pathogenetic and prognostic significance of cytokine imbalance as TRS biomarkers. This narrative review demonstrates that the problem of evaluating the contribution of pro-inflammatory and anti-inflammatory cytokines to maintaining or changing the cytokine balance can become a new key in unlocking the mystery of "non-dopamine" Sch and developing new therapeutic strategies for the treatment of TRS and psychosis in the setting of acute and chronic neuroinflammation. In addition, the inconsistency of the results of previous studies on the role of pro-inflammatory and anti-inflammatory cytokines indicates that the TRS biomarker, most likely, is not the serum level of one or more cytokines, but the cytokine balance. We have confirmed the hypothesis that cytokine imbalance is one of the most important TRS biomarkers. This hypothesis is partially supported by the variable response to immunomodulators in patients with TRS, which were prescribed without taking into account the cytokine balance of the relation between serum levels of the most important pro-inflammatory and anti-inflammatory cytokines for TRS.

Pathophysiological Mechanisms of Antipsychotic-Induced Parkinsonism.

Among neurological adverse reactions in patients with schizophrenia treated with antipsychotics (APs), drug-induced parkinsonism (DIP) is the most common motility disorder caused by drugs affecting dopamine receptors. One of the causes of DIP is the disruption of neurotransmitter interactions that regulate the signaling pathways of the dopaminergic, cholinergic, GABAergic, adenosinergic, endocannabinoid, and other neurotransmitter systems. Presently, the development mechanisms remain poorly understood despite the presence of the considered theories of DIP pathogenesis.

Blood and Urinary Biomarkers of Antipsychotic-Induced Metabolic Syndrome.

Metabolic syndrome (MetS) is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Antipsychotic (AP)-induced MetS (AIMetS) is the most common adverse drug reaction (ADR) of psychiatric pharmacotherapy. Herein, we review the results of studies of blood (serum and plasma) and urinary biomarkers as predictors of AIMetS in patients with schizophrenia (Sch). We reviewed 1440 studies examining 38 blood and 19 urinary metabolic biomarkers, including urinary indicators involved in the development of AIMetS. Among the results, only positive associations were revealed. However, at present, it should be recognized that there is no consensus on the role of any particular urinary biomarker of AIMetS. Evaluation of urinary biomarkers of the development of MetS and AIMetS, as one of the most common concomitant pathological conditions in the treatment of patients with psychiatric disorders, may provide a key to the development of strategies for personalized prevention and treatment of the condition, which is considered a complication of AP therapy for Sch in clinical practice.

Genetic Predisposition to Schizophrenia and Depressive Disorder Comorbidity.

Background: Patients with schizophrenia have an increased risk of depressive disorders compared to the general population. The comorbidity between schizophrenia and depression suggests a potential coincidence of the pathophysiology and/or genetic predictors of these mental disorders. The aim of this study was to review the potential genetic predictors of schizophrenia and depression comorbidity. Materials and Methods: We carried out research and analysis of publications in the databases PubMed, Springer, Wiley Online Library, Taylor & Francis Online, Science Direct, and eLIBRARY.RU using keywords and their combinations. The search depth was the last 10 years (2010-2020). Full-text original articles, reviews, meta-analyses, and clinical observations were analyzed. A total of 459 articles were found, of which 45 articles corresponding to the purpose of this study were analyzed in this topic review. Results: Overlap in the symptoms and genetic predictors between these disorders suggests that a common etiological mechanism may underlie the presentation of comorbid depression in schizophrenia. The molecular mechanisms linking schizophrenia and depression are polygenic. The most studied candidate genes are GRIN1, GPM6A, SEPTIN4, TPH1, TPH2, CACNA1C, CACNB2, and BCL9.Conclusion: Planning and conducting genome-wide and associative genetic studies of the comorbid conditions under consideration in psychiatry is important for the development of biological and clinical predictors and a personalized therapy strategy for schizophrenia. However, it should be recognized that the problems of predictive and personalized psychiatry in the diagnosis and treatment of schizophrenia and comorbid disorders are far from being resolved.

Association of a Single-Nucleotide Variant rs11100494 of the NPY5R Gene with Antipsychotic-Induced Metabolic Disorders.

BACKGROUND: The usage of antipsychotics (APs) is the most robust and scientifically based approach in the treatment of schizophrenia spectrum disorders (SSDs). The efficiency of APs is based on a range of target receptors of the central nervous system (CNS): serotoninergic, dopaminergic, adrenergic, histaminergic and cholinergic. Metabolic disorders are the most severe adverse drug reactions (ADRs) and lead to cardiovascular diseases with a high rate of mortality in patients with SSDs. Neuropeptide Y receptor Y5 (NPY5R) is known in the chain of interaction to target receptors for APs, agouti-related peptide receptors and proopiomelanocortin receptors. We studied the association of the single-nucleotide variants (SNVs) rs11100494 and rs6837793 of the NPY5R gene, and rs16147, rs5573, rs5574 of the NPY gene, with metabolic disorders in Russian patients with SSDs. METHODS: We examined 99 patients with SSDs (mean age-24.56 years old). The mean duration of APs monotherapy was 8 weeks. The biochemical blood test included levels of glucose, cholesterol, lipoproteins, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein and albumin. Anthropometry included weight, height, waist circumference and hip circumference. We used real-time PCR to study the carriage of major and minor alleles of the SNV rs11100494 (1164C>A) of the NPY5R gene (chromosome localization-4q32.2). Group 1 comprised 25 patients with SSDs taking APs with a change in body weight of more than 6% since the start of APs therapy. Group 2 comprised 74 patients with SSDs taking APs with a change in body weight of less than 6% since the start of APs therapy. RESULTS: We show the significance of genetic risk factors (carriage of major allele C of SNV rs11100494 of the NPY5R gene) for the development of AP-induced weight gain in Russian patients with SSDs. The allele C predisposes to AP-induced weight gain (OR = 33.48 [95% CI: 12.62; 88.82], p-value < 0.001). Additionally, the results of our study demonstrate that first-generation APs (FGAs) are more likely to cause an increase in serum transaminase levels but are less likely to increase body weight. Second-generation APs (SGAs) are more likely to cause weight gain and changes in serum glucose levels. CONCLUSION: Our study shows the predictive role of the allele C of SNV rs11100494 of the NPY5R gene in the development of AP-induced weight gain. However, we did not find a significant association between biochemical markers and this SNV in Russian patients with SSDs.

Clinical Experience of High Frequency and Low Frequency TENS in Treatment of Diabetic Neuropathic Pain in Russia.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is presently one of the main methods of treatment for neuropathic pain in type II diabetes mellitus. The discussion about which TENS frequency is more effective in the treatment of neuropathic pain has been ongoing for many years. Despite this, the response of different aspects of neuropathic pain to various TENS modalities has not been sufficiently studied. AIM: To analyze changes in characteristics of neuropathic pain depending on the frequency of TENS. MATERIALS AND METHODS: Seventy-five Russian diabetic patients with painful distal axonal neuropathy were enrolled in the study. Patients were assigned to three groups: in the HF TENS group, 25 patients received standard drug therapy (Alpha-lipoic acid, Pentoxifylline, Vitamin B12, Gabapentin) + high-frequency TENS (HF); in the LF TENS group, 25 patients received standard drug therapy (Alpha-lipoic acid, Pentoxifylline, Vitamin B12, Gabapentin) + low-frequency TENS (LF); in the control group, 25 patients underwent just standard drug therapy (Alpha-lipoic acid, Pentoxifylline, Vitamin B12, Gabapentin). Pain intensity was calculated before and after treatment with visual analogue scale (VAS), McGill pain questionnaire (MPQ), Douleur Neuropathique 4 Questions (DN4) and Pain Drawing. RESULTS: TENS increased the therapeutic effect of standard drug therapy, in the treatment of neuropathic pain, by 65.9% and prolonged its efficacy by 31% for up to 6 months after treatment. HF TENS had a more pronounced analgesic effect than LF TENS based on VAS (34.7%), sensory (57.6%) MPQ dimensions and DN4 (21%). Affective MPQ dimension with the use of LF TENS was lower than HF TENS by 34.7% immediately after treatment, by 47.3% after 2 months and by 34.8% after 6 months of the follow-up period. CONCLUSION: There are significant differences between HF and LF TENS based on pain assessment using various pain scales. This reflects the distinctive effects of different TENS modalities on different aspects of neuropathic pain.

Expression Profile of miRs in Mesial Temporal Lobe Epilepsy: Systematic Review.

Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy in children and adults. TLE is characterized by variable onset and seizures. Moreover, this form of epilepsy is often resistant to pharmacotherapy. The search for new mechanisms for the development of TLE may provide us with a key to the development of new diagnostic methods and a personalized approach to the treatment. In recent years, the role of non-coding ribonucleic acids (RNA) has been actively studied, among which microRNA (miR) is of the greatest interest. (1) Background: The purpose of the systematic review is to analyze the studies carried out on the role of miRs in the development of mesial TLE (mTLE) and update the existing knowledge about the biomarkers of this disease. (2) Methods: The search for publications was carried out in the databases PubMed, Springer, Web of Science, Clinicalkeys, Scopus, OxfordPress, Cochrane. The search was carried out using keywords and combinations. We analyzed publications for 2016-2021, including original studies in an animal model of TLE and with the participation of patients with TLE, thematic and systemic reviews, and Cochrane reviews. (3) Results: this thematic review showed that miR‒155, miR‒153, miR‒361‒5p, miR‒4668‒5p, miR‒8071, miR‒197‒5p, miR‒145, miR‒181, miR‒199a, miR‒1183, miR‒129‒2‒3p, miR‒143‒3p (upregulation), miR-134, miR‒0067835, and miR‒153 (downregulation) can be considered as biomarkers of mTLE. However, the roles of miR‒146a, miR‒142, miR‒106b, and miR‒223 are questionable and need further study. (4) Conclusion: In the future, it will be possible to consider previously studied miRs, which have high specificity and sensitivity in mTLE, as prognostic biomarkers (predictors) of the risk of developing this disease in patients with potentially epileptogenic structural damage to the mesial regions of the temporal lobe of the brain (congenital disorders of the neuronal migration and neurogenesis, brain injury, neuro-inflammation, tumor, impaired blood supply, neurodegeneration, etc.).