[Botulinum toxin type A (Relatox) in transition from medication overuse to non-overuse status in patients with chronic migraine: a subgroup analysis of phase IIIb randomized single-blind multicenter active-controlled parallel-group trial]. / Botulinicheskii toksin tipa A (Relatoks) v preodolenii lekarstvennogo zloupotrebleniya u patsientov s khronicheskoi migren'yu: podgruppovoi analiz rezul'tatov mnogotsentrovogo prostogo slepogo randomizirovannogo sravnitel'nogo issledovaniya IIIb fazy.

OBJECTIVE: To access the effect of Relatox, the first Russian botulinum toxin type A, in patients with chronic migraine (CM) and medication overuse (MO). MATERIAL AND METHODS: In phase IIIb single-blind randomized multicenter active-controlled parallel-group study, patients with CM were randomized to once intramuscular injections of Relatox (n=101) or onabotulinumtoxin A injections - Botox (n=108). This subgroup analysis evaluated the percentage of patients who transition from medication overuse to non overuse status from baseline; mean changes in the number of headache days, migraine headache days, acute headache medication intakes days, headache intensity, proportion of patients who had a ≥50% reduction in headache days, proportion of the patients with severe (≥60) Headache Impact Test-6 score and with a severe (≥21) MIDAS score in a 28-day periods in each treatment among patients with baseline acute medication overuse via repeated measures. RESULTS: Of 209 patients with CM, 100% met medication overuse criteria. Relatox and Botox demonstrated significant improvement for overall least squares mean change in headache days, migraine headache days, headache intensity; and headache-related disability and quality of life in CM patients with baseline MO, without differences between the groups. 75% and 70% patients in the Relatox and Botox groups, respectively, achieved ≥50% reduction in headache days from baseline (OR 1.58, CI 95% 0.84; 3.02, p=0.155). Furthermore, Relatox and Botox significant reduced average medication overuse rates in patient with CM and MO at baseline. 62% of patients in the Relatox group and 48% of patients in the Botox group transitioned from medication overuse to non overuse status compared from baseline (OR 2.07, CI 95% 0.91; 4.62, p=0.044). Relatox group had greater reductions than the Botox group in the percentage of patients with acute migraine-specific medication (triptan) overuse (p=0.050). CONCLUSION: The results demonstrate highly prevalent of medication overuse among individuals with CM. This analysis provides evidence that the Russian botulinum toxin type A Relatox significantly improves measures of headache symptoms, quality of life and headache-related disability, and also significantly greater, compared to Botox, reduces migraine-specific medication consumption in patients with chronic migraine who overuse acute medications.

[Botulinum toxin type A (Relatox) in the treatment of chronic migraine in adults: results of phase IIIb, randomized, one-blind, multicenter, active-controlled, parallel-group trial]. / Botulinicheskii toksin tipa A (Relatoks) v lechenii khronicheskoi migreni u vzroslykh: rezul'taty mul'titsentrovogo prostogo slepogo randomizirovannogo sravnitel'nogo issledovaniya IIIb fazy.

OBJECTIVE: To access the efficacy and safety of the first Russian botulinum toxin type A (Relatox) as a headache prophylaxis in adult with chronic migraine (CM). MATERIAL AND METHODS: The randomized, one-blind, multicenter, active-controlled, parallel-group trial study involved 209 patients with CM aged from 19 to 65 years. The patients were randomized to injections of the Russian botulinum toxin type A - Relatox (n=101) or onabotulinumtoxinA injections - Botox (n=108). The duration of the study was 16 weeks, which included five visits of patients every 4 weeks. Relatox and Botox were injected once into seven muscle groups of the head and neck at a dose of 155-195 units. Primary efficacy variable was mean change from baseline in frequency of headache days after 12 weeks. Secondary efficacy variables were mean changes from the baseline to week 12 in frequency of migraine days, acute headache pain medication intakes days; headache intensity; proportion of patients achieving ≥50% reduction from baseline in headache days, the proportion of the patients with medication overuse, the proportion of the patients with severe (≥60) Headache Impact Test-6 score and with a severe (≥21) MIDAS score. RESULTS: Analyses demonstrated a large mean decrease from baseline in frequency of headache days, without statistically significant between-group differences Relatox vs Botox at week 12 (-10.89 vs -10.06; p=0.365) and at other time points. Significant differences from baseline were also observed for all secondary efficacy variables at all time points without differences between the groups. The proportion of patients achieving ≥50% reduction from baseline in headache days was 75.0% and 70% in the Relatox and Botox groups, respectively (OR, CI 95% 1.58 [0.84; 3.02], p=0.155). Adverse events (AE) occurred in 15.8% of Relatox patients and 15.7% of Botox patients (p=1.000). No unexpected AE were identified. CONCLUSION: The results demonstrate that the first Russian botulinum toxin type A (Relatox) is an effective prophylactic treatment for CM in adult patients. Relatox led to significant improvements from baseline in multiple measures of headache symptoms, headache-related disability and quality of life. For the first time, a comparative analysis of two botulinum toxin type A products in parallel groups showed no less (not inferior) efficacy and safety of Relatox relative to Botox in the treatment of CM in adults.

The microbiome of buried soils demonstrates significant shifts in taxonomic structure and a general trend towards mineral horizons.

Burial mounds represent a challenge for microbiologists. Could ancient buried soils preserve microbiomes as they do archaeological artifacts? To investigate this question, we studied the soil microbiome under a burial mound dating from 2500 years ago in Western Kazakhstan. Two soil profile cuts were established: one under the burial mound and another adjacent to the mound surface steppe soil. Both soils represented the same dark chestnut soil type and had the same horizontal stratification (A, B, C horizons) with slight alterations. DNA samples isolated from all horizons were studied with molecular techniques including qPCR and high throughput sequencing of amplicon libraries of the 16S rRNA gene fragment. The taxonomic structure of the microbiome of the buried horizons demonstrated a deep divergence from ones of the surface, comparable to the variation between different soil types (representatives of the soil types were included in the survey). The cause of this divergence could be attributed to diagenetic processes characterized by the reduction of organic matter content and changes in its structure. Corresponding trends in the microbiome structure are obvious from the beta-diversity pattern: the A and B horizons of the buried soils form one cluster with the C horizons of both buried and surface soil. This trend could generally be designated as 'mineralization'. Statistically significant changes between the buried and surface soils microbiomes were detected in the number of phylogenetic clusters, the biology of which is in the line of diagenesis. The trend of 'mineralization' was also supported by PICRUSt2 functional prediction, demonstrating a higher occurrence of the processes of degradation in the buried microbiome. Our results show a profound shift in the buried microbiome relatively the "surface" microbiome, indicating the deep difference between the original and buried microbiomes.

[Infusion therapy with reamberin in military conditions]. / Ispol'zovanie rastvora reamberina v voennykh usloviyakh.

The article is devoted to infusion therapy with Reamberin 1.5% (Meglumine sodium succinate) in patients with various traumatic injuries. The authors substantiate the relevance and significance of this issue. Specifics and purposes of therapy are considered. The authors reviewed national studies devoted to clinical aspects and determined the main directions of therapy in emergency patients with mechanical injuries, burns, traumatic brain injury and cognitive impairment caused by combat trauma. Moreover, experimental studies of protective properties of Reamberin under combined action of cold, vibration and immobilization, as well as acute massive blood loss are analyzed.

[Safety and efficacy of the Relatox in the treatment of patients with cervical dystonia (results of a multicenter simple blind comparative randomized study)]. / Bezopasnost' i effektivnost' preparata Relatoks v lechenii patsientov s tservikal'noi distoniei (rezul'taty mul'titsentrovogo prostogo slepogo sravnitel'nogo randomizirovannogo issledovaniya).

OBJECTIVE: The analysis of evaluation of the efficacy and safety of Relatox in patients with cervical dystonia (CD). MATERIAL AND METHODS: Russian multicenter simple comparative randomized clinical trial. The study involved 180 patients of both sexes aged 18-65 years from 3 research centers of the Russian Federation. All patients had previously established diagnosis of CD and were randomized to one of two groups at 1 visit after the inclusion procedure and signing of informed consent. Patients in group 1 (n=90) got injections of Relatox, in group 2 (n=90) - injections of Botox for the first time or no earlier than 4 months after the previous injection of Dysport 500 units, Botox 200 units or Xeomin 200 units. The assessment of changes in cervical dystonia followed, including of determination of changes in the severity of CD, assessed on the TWSTRS scale by the total score and by the defining values of the blocks, as well as on the scales: the Patient Global Impression of Improvement (PGI-I) and of adverse events (local and systemic reactions). Based on the form of cervical dystonia (torticollis, laterocollis, etc.), the drug was injected under electromyographic control into the target muscles: sternocleidomastoid, belt, trapezoidal, shoulder-lifting muscle. RESULTS: Equal efficacy, good tolerability and safety comparable to the comparison drug Botox was demonstrated in 12 weeks after injection of Relatox. The number of registered local and systemic reactions in both groups was insignificant and did not differ significantly (p>0.05). There were no significant differences in the results of laboratory parameters in patients of both groups (p>0.05). Serious adverse events were also not detected during the study. CONCLUSION: Obtained results indicate the safety, good tolerability and efficacy of Relatox in patients with CD comparable to Botox and can be recomemded for using by practitioners.

[Results of a prospective observational study of the effectiveness of the complex drug Homeovox in adult patients with various types of dysphonia]. / Rezul'taty prospektivnogo nablyudatel'nogo issledovaniya effektivnosti kompleksnogo lekarstvennogo preparata gomeovoks u vzroslykh patsientov s razlichnymi vidami disfonii.

The voice as the most important means of communication is of great importance in a person's life. Every year the number of specialties for which voice and speech are a key tool of professional activity increases. Diseases of the vocal apparatus reduce the ability to work, and for some people pose a threat of professional unfitness. The relevance of the study is determined not only by the significant prevalence of dysphonia, but also by the insufficient effectiveness of existing methods of treating voice disorders. OBJECTIVE: To evaluate the clinical efficacy and safety of the use of the drug Homeovox in patients with acute and chronic catarrhal laryngitis as monotherapy. To fulfill the set goal of the study, the following tasks were solved: evaluation of the clinical effectiveness of the drug Homeovox as monotherapy for various types of dysphonia; evaluation of the effectiveness of the drug Homeovox as monotherapy from the 1st day of use. MATERIAL AND METHODS: The basis for the implementation of the tasks was the analysis of the results of the examination and treatment of 60 patients with voice disorders aged 18 to 75 years. Among them, 10 (17%) patients with acute laryngitis and 50 (83%) patients with chronic laryngitis. To establish the diagnosis, a comprehensive examination was carried out, involving examination, videolaryngostroboscopy, acoustic analysis of the voice. The study design included three patient visits, during which the functional state of the vocal apparatus was examined by subjective and objective methods. RESULTS: As a result of the treatment with the use of the drug Homeovox, the efficacy and safety of this drug in the treatment of dysphonia in adult patients with acute and chronic laryngitis from the first days of therapy has been proven, which is confirmed by the method of videolaryngostroboscopy and acoustic analysis of the voice. CONCLUSION: The drug Homeovox is an effective, safe remedy and can be included in the complex treatment of laryngeal pathology in order to increase its effectiveness and achieve a therapeutic effect in a shorter time, manifested by an improvement in the clinical and functional state of larynx.

[Higher efficacy of botulinum toxin therapy for hemifacial spasm recurrence after vascular decompression. Case report and literature review]. / Uvelichenie effektivnosti botulinoterapii pri vozvrate simptomov gemifatsial'nogo spazma posle vaskulyarnoi dekompressii. Klinicheskii sluchai i obzor literatury.

Hemifacial spasm (HFS) is an involuntary synchronous tonic and/or clonic contraction of mimic muscles following ipsilateral facial nerve dysfunction. The last one is a result of neurovascular conflict between the facial nerve and vessel. Currently, vascular decompression is a pathogenetic treatment modality for primary HFS. Various authors describe postoperative recurrence of HFS, and botulinum toxin therapy remains the only option for these patients. We aimed to describe the efficacy of botulinum toxin therapy in patients with HFS recurrence after surgical vascular decompression. The article presents a female patient with a long-term history of HFS and botulinum toxin therapy (with different formulations). Efficacy of therapy gradually decreased (progressive reduction of intervals between injections). MRI revealed a close relationship between posterior inferior cerebellar artery and roots of acoustic-facial nerves near the brainstem. The patient underwent vascular decompression of the left facial nerve root under intraoperative monitoring with positive postoperative outcome. However, HFS symptoms recurred in 3 days after surgery. Botulinum toxin type A (BTA) injections were resumed with significant positive effect that can be explained by reduction of one of the factors involved into HFS. Thus, patients with HFS recurrence after vascular decompression may benefit from BTA therapy.

[The effectiveness of botulinum therapy of trigeminal neuralgia]. / Effektivnost' botulinoterapii pri trigeminal'noi nevralgii.

OBJECTIVE: To evaluate the treatment protocol with the use of onabotulinum toxin type A (botox) and the efficacy of a single botulinum therapy procedure for clinical manifestations in patients with trigeminal neuralgia (TN). MATERIAL AND METHODS: We studied 90 patients (57 women, 33 men), including 80 people with primary TN and 10 people with secondary TN. Then 20 patients with primary TN (11 women and 9 men, mean age 61.8 years) received local injections of onabotulinum toxin type A (botox). Clinical examination included taking anamnesis, assessment of pain on a visual analogue scale (VAS), assessment of the frequency of pain paroxysms, taking into account the average indicator (0 to 100 seizures during the day); neurosensory examination according to the developed protocol with the definition of pain, temperature, tactile sensitivity, the study of stimulus-dependent pain; MRI of the brain to diagnose neurovascular conflict. RESULTS: A month after the injections, the pain intensity practically did not change (8.5 versus 7.2 points on the VAS), but the number of paroxysms decreased (31.2 versus 22.5 seizures per day). Two months after the use of botox, the number of pain attacks continued to decrease (31.2 versus 17.7; Mann-Whitney U-test, p=0.006). At the same time, there was a decrease in pain intensity according to the VAS (8.5 versus 6.1, t-test 2.75 points; p=0.02). After three months, there was a decrease in the number of paroxysms from 31.2 to 9.2 (paired Student's test, p<0.001) and the severity of pain (8.85 versus 4.0 points on the VAS, paired t-test 3.95 points, p<0.001). There were significant differences in the average dose of carbamazepine (867.5 versus 670.8 after 3 months, t-test 196.7 mg, p=0.02). In TN patients who underwent destructive operations with exposure to the peripheral branches of the trigeminal nerve, signs of severe neurosensory deficit on the face and burning pain are added to the main symptoms, which corresponds to the clinical criteria of post-traumatic trigeminal neuropathy. CONCLUSION: Local injections of type A onabotulinum toxin (botox) are minimally invasive, safe and effective symptomatic therapy for patients with TN. Persistent sensory disturbances that develop in patients after destructive surgeries call into question the safety of these therapies for TN.

[Botulinum therapy of spastic forms of cerebral palsy in various locomotor patterns]. / Botulinoterapiya spasticheskikh form detskogo tserebral'nogo paralicha pri razlichnykh lokomotornykh patternakh.

Spasticity in patients with cerebral palsy (CP) is the main impediment to normal locomotion. The function of the Central Pattern Generator (CPG), i.e. a group of neural chains in the spinal cord, stands at the core of any rhythmical movement. CPG can generate locomotion patterns without supraspinal control, which can have both positive and negative impact on the ability to move. Performing the motor tasks such as walking, running and swimming, creates the consistent rhythmical movement of legs and arms through interaction between CPGs of upper and lower extremities. This interaction can cause the activation of pathological movement patterns in lower extremities in response to upper limb spasticity. Thus, neural chains in the spinal cord become the generator of pathologically increased excitation which has developed as a result of a focal lesion in the CNS. All the statements described above show the importance of introducing the upper limb injections of bFotulinum toxin A in the protocol in order to develop normal locomotion. The PUL study approved the optimal level of efficacy and favourable safety profile of botulinum toxin A in children with CP and upper limb muscle spasticity.

Application of real-time PCR to significantly reduce the time to obtain recombinant MVA virus.

Obtaining a pure recombinant Modified Vaccinia Ankara (MVA) virus is a multistage, time-consuming procedure. We describe a novel single-tube real-time PCR which enables determination of the amount of wild type and recombinant viruses and their ratio in plaques. Use of the real-time PCR significantly reduce the time and efforts needed to obtain purified recombinant MVA. The new approach has been applied to generate recombinant MVAs encoding different SARS-COV-2 antigens.

[Short peptides: regulation of skin function during aging.]

Short peptides are applied for supporting skin function during ageing, because they can permeate the intact stratum corneum of the epidermis and affect the cells of the dermis. Short peptides are part of natural metabolism of cells and many of them have geroprotective properties. In the review we are considering the base sorts of peptides that are used for normalized skin fibroblasts function: matrikines, carnosine, collagen peptides, cytokine and growth factor analogs, defensins, immunoprotective peptides and polyfunctional peptides. Polyfunctional peptides (AcSDKP, KED, AEDG, AED) have geroprotective properties, slow apoptosis and stimulate skin cell proliferation, also increase functional activity of skin fibroblasts, normalize intracellular matrix hemostasis. Polyfunctional peptides are the antioxidants and immunoprotectors and can activate microcirculation in dermis. Peptide regulation of skin function during ageing are the fast-developing and prospective area in molecular gerontology.

Analysis of Antitumor Activity of the Liposomal Photosensitizer Lipophthalocyan.

We studied specific antitumor activity of a liposomal drug based on tetra-3-phenylthiophthalocyanine aluminum hydroxide (lipophthalocyan) intended for photodynamic therapy. The optimal dose and protocol for photodynamic therapy with lipophthalocyan were chosen in experiments on mice: single intravenous dose of 6 mg/kg with a 5-h interval between administration and laser exposure and irradiation energy density of 400 J/cm2. A wide spectrum antitumor activity of lipophthalocyan was demonstrated in vivo for various transplantable mouse tumors (Lewis lung epidermoid carcinoma, S37 sarcoma, and colon adenocarcinoma AKATOL). The results show the possibility of using lipophthalocyan for photodynamic therapy of tumors of surface localization (skin and mucosa tumors).

[Mathematical Modeling of the Intracellular Regulation of Immune Processes].

The modern era of research in immunology is characterized by an unprecedented level of detail about structural characteristics of the immune system and the regulation of activities of its numerous components, which function together as a whole distributed-parameter system. Mathematical modeling provides an analytical tool to describe, analyze, and predict the dynamics of immune responses by applying a reductionist approach. In modern systems immunology and mathematical immunology as a new interdisciplinary field, a great challenge is to formulate the mathematical models of the human immune system that reflect the level achieved in understanding its structure and describe the processes that sustain its function. To this end, a systematic development of multiscale mathematical models has to be advanced. An appropriate methodology should consider (1) the intracellular processes of immune cell fate regulation, (2) the population dynamics of immune cells in various organs, and (3) systemic immunophysiological processes in the whole host organism. Main studies aimed at modeling the intracellular regulatory networks are reviewed in the context of multiscale mathematical modelling. The processes considered determine the regulation of the immune cell fate, including activation, division, differentiation, apoptosis, and migration. Because of the complexity and high dimensionality of the regulatory networks, identifying the parsimonious descriptions of signaling pathways and regulatory loops is a pressing problem of modern mathematical immunology.

Emergence of Candida auris in Russia.

This paper reports the emergence of Candida auris infections in an intensive care unit at a hospital in Moscow. Forty-nine cases were diagnosed in 2016-2017, and the risk factors and antifungal susceptibilities are described. The 30-day all-cause mortality for 19 bloodstream infections in patients who did not receive appropriate antifungal therapy was 42.1%. Phylogenetic analysis of the internal transcribed spacer and D1-D2 regions and K143R substitution in the ERG11 gene indicated that the studied C. auris strains were of South Asian origin. This first reported series of C. auris infections in Russia demonstrates the rapid dissemination of this species, and the need for international surveillance and control measures.

[Aging of skin fibroblasts: genetic and epigenetic factors.]

Gerontocosmetology is the rapid developing knowledge area that has a very large applied meaning. Herewith a lot of information about skin aging and geroprotectors for skin rejuvenation hasn't a scientific background. Thus, understanding the fundamental mechanisms of skin aging becomes the actual task of molecular gerontology. Skin fibroblasts are the polyfunctional cell population that synthesize a number of biologically active substances and participate in maintaining of extracellular matrix homeostasis, skin hydratation and endocrine and immune function. In the review genetic (accumulation of nuclear and mitochondrial DNA mistakes) and epigenetic factors of skin fibroblasts aging are described. Role of AP-1, NF-κB, c-jun, CCN1, TGF-ß, TNF-α, MMP-1, MMP-3, MMP-8, MMP-9 and glycation in skin fibroblasts aging are discussed. There are some data about decreasing of skin fibroblasts ability to migration and synthesis of paxillins and aquaporin-3 (AQP3) during aging. Role of hormonal regulation in skin fibroblasts aging are described. Geroprotective action of melatonin to skin fibroblasts are showed. Reviewed molecular-cellular aspects of skin fibroblasts aging can be take into consideration for scientific background of using of cosmetic products for retarding of skin aging rate.

[The efficacy of botulinum therapy in treatment of delayed facial palsy after resection of vestibular schwannoma]. / Éffektivnost' botulinoterapii v lechenii otsrochennoi neiropatii litsevogo nerva posle udaleniia nevrinomy slukhovogo nerva.

Delayed facial palsy is a complication developing 3 or more days after surgery. The etiology and pathogenesis of this condition has not been fully explored, and there are no treatment standards for it. As in the case of Bell's paralysis, glucocorticosteroids (GCSs) are currently used to treat delayed facial palsy. However, patients with contraindications to GCSs need new therapy modalities. AIM: We aimed to evaluate the efficacy and safety of botulinum therapy in patients with delayed facial palsy after neurosurgical interventions. MATERIAL AND METHODS: We examined 33 patients with delayed facial palsy developed 3 or more days after resection of vestibular schwannoma. The main group included 18 patients with contraindications to GCSs who received injections of botulinum toxin A (BTA) into the facial muscles of the healthy side for muscle relaxation. The comparison group consisted of 15 patients who received a course of prednisolone (1 mg/kg/day) for 5-7 days. The efficacy of treatment was assessed using the House-Brackmann scale and Clinical Global Impression Scale. The follow-up period after therapy was 3 months. RESULTS: Delayed facial palsy was more common in the following cases: the facial nerve was located near the antero-inferior tumor pole; the tumor was adherent to the facial nerve; the tumor extended in the oral direction; the tumor had with unclear borders and was 11 to 30 mm in size. In most patients of both groups, facial muscle palsy developed more than 11 days after surgery. Treatment both in the main and control groups resulted in a significant improvement: complete regression of the facial asymmetry in patients of the main group and comparison groups 3 months after treatment onset was 83.3 and 93.3% (House-Brackmann scale), respectively. CONCLUSION: Botulinum therapy may be recommended for patients with delayed facial palsy developed after vestibular schwannoma resection, who have contraindications to GCSs.

Influence of monostrain and multistrain probiotics on immunity, intestinal ultrastructure and microbiota in experimental dysbiosis.

The biological effects of three probiotic strains Lactobacillus rhamnosus K32, Bifidobacterium longum GT15, Enterococcus faecium L3 and their mixture were studied using a model of dysbiosis induced in rats by antibiotics. It was found that after taking different probiotics intestinal microbiota changed in a strain-specific manner. The maximal activity against pathogens was revealed after the administration of a mixture of bacterial strains under study or a single strain of enterococci. The strain E. faecium L3 showed the most activity against both Klebsiella spp. and Bacteroides fragilis. It helped to restore the original content of Faecalibacterium prausnitzii. The number of Klebsiella spp. was the same in the group receiving L. rhamnosus K32 and the group of animals, which was not consuming probiotics. Different probiotic strains included in the composition had various immunological effects. Probiotic bifidobacteria, enterococci and the mixture of three probiotics stimulated of mRNA expression of interleukin (IL)-10 in mesenteric lymph nodes. The changes in microbiota after consuming an enterococcal probiotic correlated with an increase in transforming growth factor (TGF)-ß and IL-10 content in blood serum and an increase of the intestinal mucus layer. Consumption of L. rhamnosus K32 led to the stimulation of IL-8 expression in mesenteric lymph nodes. Control group not receiving probiotics was characterised by expression of pro-inflammatory cytokines, damage of epithelial cells and the destruction of their tight junctions. The damage to the ultrastructure of the mucosa was prevented in all the groups taking probiotics.

[Facial nerve injury in neurosurgery: a rehabilitation potential of botulinum therapy]. / Porazhenie litsevogo nerva pri neirokhirurgicheskikh operatsiiakh: reabilitatsionnyi potentsial botulinoterapii.

Surgical treatment of posterior cranial fossa and cerebellopontine angle tumors is associated with a risk of facial nerve dysfunction. The causes for facial muscle paresis include nerve compression by the tumor, destruction of the nerve structure by the tumor growing from nerve fibers, nerve injury during surgical removal of the tumor, etc. The first 3 months after facial nerve injury are a potential therapeutic window for the use of botulinum toxin type A (BTA). During this period, the drug is introduced both in the healthy side to improve the facial symmetry at rest and during mimetic movements and in the affected side to induce drug-induced ptosis. Post-paralytic syndrome develops 4-6 months after facial nerve injury. At this stage, administration of BTA is also an effective procedure; in this case, drug injections are performed on the affected side at small doses and symmetrically on the healthy side at doses doubling those for the affected side. BTA injections are mandatory in complex treatment of facial muscle paralysis.

[Conversion ratio between different botulinum neuroprotein product in neurological practice]. / Sootnoshenie edinits deistviia razlichnykh preparatov botulinicheskogo neiroproteina pri ispol'zovanii v nevrologicheskoi praktike.

Despite nearly 30 years of experience in the application of botulinum toxin type A (BTA) in clinical practice, many fundamental questions of therapy remain valid. There are 5 botulinum toxin type A used for neurological indications in the Russian Federation in 2017. They contain different number of active neuroprotein (150 kDa) in a therapeutic dose of the drug that may have a potential impact on the efficacy and duration of action. The current SmPC of each BTA stated that the unit of activity is unique and can not be compared with any other BTA. In scientific publications one can find many details concerning the equivalence doses of onabotulinumtoxin A (botox) and abobotulinumtoxin A (dysport) and the ratio of units varies from 1:1 to 1:11. However, according to clinical guidelines, systematic reviews and high quality research evidence of recent years, the ratio of units of abobotulinumtoxin A (dysport) and onabotulinumtoxin A (botox) is 3(2,5):1. Use of a fixed ratio of units is possible only when switching from one drug to another or in case of limiting access to specific drug. Botulinum toxin type A is the first line of therapy in the treatment of several neurological diseases. The most commonly used drugs of botulinum toxin type A (botox, dysport, xeomin) have a significant evidence base that confirms their efficacy and optimal safety profile. The main difference between botulinum toxin type A is their potential activity of action, i.e., activity units and total therapeutic dose.

[Transcription factor p53 and skin aging].

The review is devoted to an actual problem of cosmetics in gerontology, one of molecular aspects of skin aging. Cell renewal processes slow down with aging, and the proliferation apoptosis ratio shifts towards cell death. One of the most pivotal apoptotic markers is the transcription factor p53. p53 protein expression in the skin keratinocytes increases under the influence of ultraviolet radiation. Wherein when exposed to ultraviolet radiation mutant forms of p53 have been revealed in 70 % of keratinocytes. On the one hand, suppression of p53 expression decreases apoptosis in skin cells that slows down the process of aging. On the other hand, it promotes the development of tumors in the skin. Thus, maintaining the physiological balance of p53 expression in skin cells is important for the basic and practical cosmetic medicine in gerontology. In addition, p53 protein may be used as a functionality marker of skin cells when administered with geroprotective cosmetic means and instrumental cosmetology methods.