[Investigation of oncolytic potential of vaccine strains of yellow fever and tick-borne encephalitis viruses against glioblastoma and pancreatic carcinoma cell lines].

INTRODUCTION: Flaviviruses, possessing natural neurotropicity could be used in glioblastoma therapy using attenuated strains or as a delivery system for antitumor agents in an inactivated form. OBJECTIVE: To investigate the sensitivity of glioblastoma and pancreatic carcinoma cell lines to vaccine strains of yellow fever and tick-borne encephalitis viruses. MATERIALS AND METHODS: Cell lines: glioblastoma GL-6, T98G, LN-229, pancreatic carcinoma MIA RaCa-2 and human pancreatic ductal carcinoma PANC-1. Viral strains: 17D yellow fever virus (YF), Sofjin tick-borne encephalitis virus (TBEV). Virus concentration were determined by plaque assay and quantitative PCR. Determination of cell sensitivity to viruses by MTT assay. RESULTS: 17D YF was effective only against pancreatic carcinoma tumor cells MIA Paca-2 and had a limited effect against PANC-1. In glioblastoma cell lines (LN229, GL6, T98G), virus had no oncolytic effect and the viral RNA concentration fell in the culture medium. Sofjin TBEV showed CPE50 against MIA Paca-2 and a very limited cytotoxic effect against PANC-1. However, it had no oncolytic effect against glioblastoma cell lines (LN229, T98G and GL6), although virus reproduction continued in these cultures. For the GL6 glioblastoma cell line, the viral RNA concentration at the level with the infection dose was determined within 13 days, despite medium replacement, while in the case of the LN229 cell line, the virus concentration increased from 1 × 109 to 1 × 1010 copies/ml. CONCLUSION: Tumor behavior in organism is more complex and is determined by different microenvironmental factors and immune status. In the future, it is advisable to continue studying the antitumor oncolytic and immunomodulatory effects of viral strains 17D YF and Sofjin TBEV using in vivo models.

[Decompression fusion surgery and minimally invasive microsurgical decompression in patients with single-segment lumbar spinal stenosis]. / Sravnitel'nyi analiz rezul'tatov primeneniya metodik dekompressii so stabilizatsiei i minimal'no invazivnoi mikrokhirurgicheskoi dekompressii u patsientov s monosegmentarnym poyasnichnym spinal'nym stenozom.

There are few studies comparing clinical efficacy of decompression/fusion surgery (transforaminal lumbar interbody fusion (TLIF) + transpedicular interbody fusion) and minimally invasive microsurgical decompression (MMD) in patients with single-segment lumbar spinal stenosis. OBJECTIVE: To compare the results of TLIF + transpedicular interbody fusion and MMD in patients with single-segment lumbar spinal stenosis. MATERIAL AND METHODS: A retrospective observational cohort study included medical records of 196 patients (100 (51%) men, 96 (49%) women). Age of patients ranged from 18 to 84 years. Mean postoperative follow-up period was 20.1±6.7 months. Patients were divided into 2 groups: group I (control) included 100 patients who underwent TLIF + transpedicular interbody fusion, group II (study) included 96 patients who underwent MMD. We analyzed pain syndrome and working capacity using visual analogue scale (VAS) and Oswestry Disability Index (ODI), respectively. RESULTS: Analysis of pain syndrome in both groups after 3, 6, 9, 12 and 24 months clearly demonstrated stable relief of pain syndrome (VAS score) in the lower extremities. In group II, VAS score of lower back and leg pain was significantly higher in long-term follow-up period (after 9 months or more) compared to the 1st group (p<0.05). In long-term follow-up period (after 12 months), there was significant decrease in degree of disability (ODI score) in both groups (p<0.001) without between-group differences. We assessed achievement of treatment goal in 12 and 24 months after surgery in both groups. The result was significantly better in the 2nd group. At the same time, some respondents failed to achieve the final clinical goal of treatment in both groups (group I - 8 (12.1%), group II - 2 (3%) patients). CONCLUSION: Analysis of postoperative outcomes in patients with single-segment degenerative lumbar spinal stenosis revealed similar clinical effectiveness of TLIF + transpedicular interbody fusion and MMD regarding decompression quality. However, MMD was associated with less traumatization of paravertebral tissues, blood loss, fewer unwanted phenomena and earlier recovery.

[Minimally invasive microsurgical decompression in patients with monosegmental lumbar spinal stenosis]. / Rezul'taty primeneniya minimal'no invazivnoi mikrokhirurgicheskoi dekompressii u patsientov s monosegmentarnym poyasnichnym stenozom.

Surgical treatment of degenerative lumbar spinal stenosis is an actual problem of modern spinal surgery and orthopedics. OBJECTIVE: To analyze the results of minimally invasive microsurgical decompression (MI-MD) in patients with monosegmental lumbar spinal stenosis. MATERIAL AND METHODS: A retrospective observational cohort study was performed. We analyzed medical records of patients who underwent MI-MD for monosegmental degenerative lumbar spinal stenosis. Clinical and objective results of MI-MD, as well as the types and prevalence of adverse clinical events were studied. RESULTS: The study included 96 medical records (50 (52%) males and 46 (48%) females aged 18-84 years). Analysis of pain in lower back and lower extremities in 3, 6, 9, 12 and 24 months after MI-MD showed a significant decrease of this indicator (p<0.001). There was significant improvement of capacity according to ODI score up to 5-12% in 72.9% of patients in early postoperative period (p=0.055). In delayed postoperative period, we also observed significant improvement of working capacity according to ODI score and gradual decrease in disability index (p<0.001). Adverse clinical events occurred in 6 (6.2%) patients. CONCLUSION: MI-MD is a highly effective surgical method for monosegmental lumbar spinal stenosis with minimal incidence of adverse clinical events.

Increased LAMP1 Expression Enhances SARS-CoV-1 and SARS-CoV-2 Production in Vero-Derived Transgenic Cell Lines.

Coronaviridae is a family of single-stranded RNA (ssRNA) viruses that can cause diseases with high mortality rates. SARS-CoV-1 and MERS-CoV appeared in 2002‒2003 and 2012, respectively. A novel coronavirus, SARS-CoV-2, emerged in 2019 in Wuhan (China) and has caused more than 5 million deaths in worldwide. The entry of SARS-CoV-1 into the cell is due to the interaction of the viral spike (S) protein and the cell protein, angiotensin-converting enzyme 2 (ACE2). After infection, virus assembly occurs in Golgi apparatus-derived vesicles during exocytosis. One of the possible participants in this process is LAMP1 protein. We established transgenic Vero cell lines with increased expression of human LAMP1 gene and evaluated SARS-CoV-1 and SARS-CoV-2 production. An increase in the production of both viruses in LAMP1-expressing cells when compared with Vero cells was observed, especially in the presence of trypsin during infection. From these results it can be assumed that LAMP1 promotes SARS-CoV-1 and SARS-CoV-2 production due to enhanced exocytosis.

[Increased LAMP1 Expression Enhances SARS-CoV-1 and SARS-CoV-2 Production in Vero-Derived Transgenic Cell Lines].

Coronaviridae is a family of single-stranded RNA (ssRNA) viruses that can cause diseases with high mortality rates. SARS-CoV-1 and MERS-CoV appeared in 2002-2003 and 2012, respectively. A novel coronavirus, SARS-CoV-2, emerged in 2019 in Wuhan (China) and has caused more than 5 million deaths in worldwide. The entry of SARS-CoV-1 into the cell is due to the interaction of the viral spike (S) protein and the cell protein, angiotensin-converting enzyme 2 (ACE2). After infection, virus assembly occurs in Golgi apparatus-derived vesicles during exocytosis. One of the possible participants in this process is LAMP1 protein. We established transgenic Vero cell lines with increased expression of human LAMP1 gene and evaluated SARS-CoV-1 and SARS-CoV-2 production. An increase in the production of both viruses in LAMP1-expressing cells when compared with Vero cells was observed, especially in the presence of trypsin during infection. From these results it can be assumed that LAMP1 promotes SARS-CoV-1 and SARS-CoV-2 production due to enhanced exocytosis.

[Degenerative lumbar spine stenosis: minimally invasive microsurgical methods of treatment]. / Degenerativnyi stenoz poyasnichnogo otdela pozvonochnika: kharakteristika minimal'no invazivnykh mikrokhirurgicheskikh metodov lecheniya.

Degenerative lumbar spine stenosis is one of the main causes of chronic pain and radiculopathy in advanced age people. Along with increase in average life expectancy, degenerative lumbar spine stenosis becomes the most common indication for spinal surgery. There is still no consensus regarding the most optimal surgical approach due to the variety of modern surgical methods. In recent years, minimally invasive spinal surgery has become a more advisable alternative to open surgery due to its advanced technical features combined with less soft tissue damage, lower risk of complications and shorter postoperative recovery.

[Intraoperative computed tomography and modern navigation in surgical treatment of spine and spinal cord diseases]. / Opyt primeneniya intraoperatsionnogo spiral'nogo komp'yuternogo tomografa i sovremennoi sistemy navigatsii v khirurgicheskom lechenii zabolevanii pozvonochnika i spinnogo mozga.

Surgical treatment of spine and spinal cord diseases is one of important objectives in modern neurosurgery. Patient safety is a priority in spine and spinal cord surgery. Intraoperative imaging ensures efficacy and safe surgery with and without stabilization, preoperative marking, control of decompression and correct implant placement. Surgical C-arms and intraoperative cone-beam CT scanners are the most widespread in everyday practice. The latest achievement was intraoperative spiral computed tomography. C-arms and CT scanners with intraoperative navigation increase the efficiency and safety of surgical interventions.

Detection of SARS-CoV-2 RNA in nasopharyngeal swabs from COVID-19 patients and asymptomatic cases of infection by real-time and digital PCR.

In this work we tested two reagent kits developed by us for detecting SARS-CoV-2 RNA using a fragment of the ORF1ab gene in digital PCR and real-time PCR formats. Data were obtained on the detection of SARS-CoV-2 virus RNA in nasopharyngeal swabs of patients with COVID-19 and asymptomatic carriers. The developed reagent kits provided 100% sensitivity and a detection limit of 103 GE / ml for qPCR, and at least 200 copies / ml of viral RNA when performing digital PCR. These methods were tested using a panel of 1,328 samples collected from patients with suspected COVID-19 at the beginning of 2020 in the Russian Federation. It has been shown that dPCR is more sensitive and can be used to analyze samples with low viral load, including those from patients without clinical symptoms. dPCR significantly improves the accuracy of laboratory research and significantly reduces the number of false negative results in the diagnosis of SARS-CoV-2. Determination of the concentration of SARS-CoV-2 RNA in patients with different clinical course of the disease showed that the concentration of viral RNA can sharply decrease in the first days of the disease. A low concentration of viral RNA in samples from patients is also characteristic of asymptomatic disease. Digital PCR provides a higher detection rate for asymptomatic cases, which is approximately 75% of those infected, as opposed to 45% for real-time PCR. The results obtained on the use of the digital PCR method for detecting SARS-CoV-2 RNA showed that this method is especially suitable for detecting RNA in case of its low concentration in contacts, as well as for monitoring changes in viral load in convalescent patients.

Phase states, microstructure and dielectric characteristics of solid solutions (1 - x)NaNbO3 - xCa2Nb2O7 and (1 - x)NaNbO3 - xSr2Nb2O7.

Ceramics of binary systems solid solutions (1 - x)NaNbO3 - xCa2Nb2O7 and (1 - x)NaNbO3 - xSr2Nb2O7 with non-isostructural extreme components were prepared by the solid-phase reactions technique with the following sintering using conventional ceramic technology. It was found that ceramics with x ≤ 0.2 have a perovskite structure. Layered type of structure predominates in the concentration range 0.2 < x ≤ 1. Phase diagrams of both systems at room temperature have been determined in the perovskite area. It was shown that this area contains two concentration regions with the different crystal structures and the morphotropic phase boundary between them. Microstructure and dielectric characteristics of selected solid solutions were investigated. The influence of technological regulations, such as mechanical activation and variation of sintering temperatures, on the formation of the microstructure and dielectric characteristics was studied for the individually selected concentrations (x = 0.1 and x = 0.25). Dielectric characteristics of ceramics revealed the presence of the Maxwell-Wagner polarization and its corresponding relaxation in the solid solutions (1 - x)NaNbO3 - xCa2Nb2O7 at x > 0.20.

Intercalation of water molecules from the air into perovskite and layered structures formed in the system of NaNbO3-Ca2Nb2O7.

The study results of the perovskite solid solution and layered compounds formed in the system of (1-х)NaNbO3-xCa2Nb2O7, x = 0.10, 0.25, 0.55, 1.00 are presented. The objects of the study are obtained by solid-phase synthesis, followed by sintering using conventional ceramic technology. The study of dielectric spectra has revealed their anomalous behavior in the temperature range of 360-450 K, most pronounced in the composition with x = 0.25. To explain the anomalies in these objects, a microstructural analysis of ceramics, thermogravimetry, high-temperature powder X-ray diffraction, and IR spectroscopy heve been performed. It has been established that the anomalies of the dielectric spectra in the indicated range are due to the adsorption of water from the air, its dissociation and the incorporation of the OH2 and OH- oxyhydryl groups into the crystal lattice of the solid solution and the compounds. In a compound located near the boundary between solid solutions and layered compounds, the process of water adsorption is accompanied by the appearance of an intermediate incommensurate phase and ends with the formation of a new compound.

[Systematic Analysis of the Roles of Trace Elements in the Prevention and Treatment of Chronic Heart Failure].

Systematic analysis of 3 728 publications on the relationship between microelement status and chronic heart failure (CHF) was carried out. Three main areas of research have been identified: 1) magnesium, electrolytes and CHF; 2) the transcriptional and antioxidant effects of zinc, selenium, copper; 3) iron-deficiency anemia and CHF. In this paper, we consider a complex of relationships between the magnesium insufficiency and CHF, the effect of magnesium on vascular tone, mitochondria, heart rhythm and the susceptibility of cardiomyocytes to adrenergic stimulation. Using magnesium orotate for the treatment of CHF is a feasible approach to compensate magnesium insufficiency in patients with CHF.

[Monitoring of adverse event triggers as a tool for managing the medical care quality at a neurosurgical clinic. Invitation to the discussion]. / Monitoring triggerov neblagopriiatnykh sobytii kak instrument upravleniia kachestvom meditsinskoi pomoshchi v neirokhirurgicheskoi klinike. Priglashenie k diskussii.

Management of the healthcare quality and safety is one of the priorities of state policy for protecting health of Russian citizens. We describe modern technologies for managing the quality of medical care and patient safety based on a systematic approach. Potential applications of these technologies in neurosurgical practice are defined. Quantitative, qualitative, and basic indicators are proposed for evaluation of outcomes (results) as part of implementation of an integrated quality management system in neurosurgical practice.

[Intraoperative video-angiography in surgery for spinal intramedullary cavernous malformations: first experience of its application at the Burdenko Neurosurgical Center]. / Intraoperatsionnaia videoangiografiia v khirurgii intramedulliarnykh kavernoznykh mal'formatsii spinnogo mozga: pervyi opyt ispol'zovaniia v FGAU 'Natsional'nyi meditsinskii issledovatel'skii tsentr neirokhirurgii im. akad. N.N. Burdenko'.

Spinal intramedullary cavernous malformations are a rare vascular pathology of the central nervous system. They account for 3-5% of spinal cord diseases. The clinical picture in patients with cavernous malformations varies from an asymptomatic course to gross neurological deficit in the case of bleeding from a malformation. Due to the lack of reliable methods for predicting the development of bleeding, the need for surgical treatment of asymptomatic patients remains a relevant and open topic for discussion. The goal of surgical treatment of cavernous malformations is to minimize the risk of repeated hemorrhages and gross neurological deficits in patients. Intraoperative indocyanine green video angiography is a promising technique for intraoperative visualization of the size and adherence area of a cavernous malformation to the spinal cord tissue. This increases the radicality of cavernous malformation resection and minimizes intraoperative risks for the patient.

[Experience with mexidol in neurological practice]. / Opyt primeneniia meksidola v nevrologicheskoi praktike.

Antihypoxic, antioxidant and nootropic effects of mexidol contribute to the improvement of patients with cerebrovascular pathology. The results of clinical studies show that the sequential scheme of using mexidol (first i.v. or i.m., then per os) is effective in the complex therapy of ischemic diseases of the brain, vascular surgery, therapy and rehabilitation of patients with degenerative-dystrophic changes of the spine, treatment of neurodegenerative pathology (including multiple sclerosis, Parkinson's disease and diabetic polyneuropathy), infectious neuropathies (ARVI, herpes, tick-borne encephalitis), neuropsychological and autonomic disorders.

Case Report: Education and training of RTTs for radiation oncology departments in Russia.

Modern radiotherapy is performed with sophisticated equipment that requires highly qualified professionals. In the Russian Federation the responsibilities of Radiation Therapy Technologists (RTTs) are carried out by medical nurses who receive on-the-job training. The article discusses the problems of RTT education and training, describes our own teaching experience and suggests further development for the national RTT education system in Russia.

[Results of surgical treatment for lumbar spine segmental instability]. / Rezul'taty khirurgicheskogo lecheniia nestabil'nosti pozvonochno-dvigatel'nogo segmenta poiasnichnogo otdela pozvonochnika.

AIM: To perform a comparative analysis of outcomes in patients with lumbar spine segmental instability who underwent surgical treatment using transforaminal lumbar interbody fusion (TLIF) and direct lateral interbody fusion (DLIF) techniques. MATERIAL AND METHODS: The multicenter study involved 209 patients who underwent surgery for lumbar spine segmental instability. Long-term outcomes (up to 2 years) were studied in 134 patients: patients of the first group (98 patients) underwent traditional transforaminal lumbar interbody fusion (TLIF) and transpedicular stabilization of vertebral segments; patients of the second group (36 patients) underwent direct lateral interbody fusion (DLIF) in combination with transpedicular stabilization of the lumbar vertebral segments. We used standard checkpoints for monitoring the patients' condition: before surgery, at discharge, at 3, 6 and, 9 months, and at 1 and 2 years after surgery. To follow-up the patients, we used the Visual Analogue Scale, Oswestry Disability Index, and Goal Attainment Scaling. RESULTS: A comparative analysis of the two interbody fusion techniques was enabled by the developed Vertebrologic Registry profile (http://spineregistry.ru/Register_treatment.php) that was designed for entering data of Russian and foreign experts to analyze clinical characteristics, evaluate outcomes, and follow-up patients with degenerative lumbosacral spine diseases. In both groups of patients, a significant decrease in the pain intensity in the lumbar spine and lower extremities (VAS) occurred in the immediate postoperative period, which persisted in the long-term period. There were no differences in the disability level (Oswestry index) in both groups of patients (p<0.05). An analysis of treatment goal attainments one year after surgery revealed the best result in patients of the second group who underwent DLIF. CONCLUSIONS: 1. Indirect decompression using direct lateral interbody fusion (DLIF) minimizes the risks of intraoperative injury to the dura mater and neural structures. Kawabata class I outcomes (good) were achieved in 89% of patients who underwent direct lateral spinal fusion (DLIF) and in 81% of patients who underwent transforaminal interbody stabilization in combination with transpedicular fixation.

An artificial metalloenzyme with the kinetics of native enzymes.

Natural enzymes contain highly evolved active sites that lead to fast rates and high selectivities. Although artificial metalloenzymes have been developed that catalyze abiological transformations with high stereoselectivity, the activities of these artificial enzymes are much lower than those of natural enzymes. Here, we report a reconstituted artificial metalloenzyme containing an iridium porphyrin that exhibits kinetic parameters similar to those of natural enzymes. In particular, variants of the P450 enzyme CYP119 containing iridium in place of iron catalyze insertions of carbenes into C-H bonds with up to 98% enantiomeric excess, 35,000 turnovers, and 2550 hours-1 turnover frequency. This activity leads to intramolecular carbene insertions into unactivated C-H bonds and intermolecular carbene insertions into C-H bonds. These results lift the restrictions on merging chemical catalysis and biocatalysis to create highly active, productive, and selective metalloenzymes for abiological reactions.

[Postoperative applications of the fast track technology in patients with herniated intervertebral discs of the lumbosacral spine]. / Primenenie tekhnologii bystrogo vosstanovleniya posle khirurgicheskikh vmeshatel'stv u patsientov s gryzhami mezhpozvonkovykh diskov poyasnichno-kresttsovogo otdela pozvonochnika.

TOPICALITY: The fast track technology means a complex of targeted measures involving rational preoperative preparation, minimally invasive surgery, regional anesthesia and short-acting anesthetics, and early postoperative rehabilitation. Elucidating the possibility of applying the fast track technology in neurosurgery, in particular in spinal surgery, is extremely topical. This is associated with the epidemiological data and the fact that minimally invasive techniques used in neurosurgery are highly expensive. AIM: The study objective was implementation of the fast track technology and subsequent analysis of its use after surgery in patients with herniated intervertebral discs of the lumbosacral spine. MATERIAL AND METHODS: The fast track technology following spinal surgery was implemented at the Clinical Hospital of the Presidential Administration of the Russian Federation and the Neurosurgical Department of the Clinical Hospital № 1 of the Presidential Administration of the Russian Federation using an algorithm of technology application. The study included 48 patients who underwent surgical treatment for herniated intervertebral discs of the lumbosacral spine between January and July 2015. RESULTS: An analysis of pain severity using the Visual Analog Scale demonstrated a slight decrease (10%) in a group of patients who were subjected to the fast track technology, at discharge and at 1 month after surgery; there was no difference in longer follow-up. An analysis of the functional status using the Oswestry index and Roland-Morris scale demonstrated that patients of the study group had faster and more efficient recovery and an improvement of the functional activity by 20% (p<0.05) compared to those in the control group. An analysis of patient-reported assessment of treatment quality revealed that indicators, such as awareness and pain control, in the study group were highest and amounted to 95% and higher. An analysis of the hospital stay duration showed a decrease in the number of bed-days in an integrated group by 39%, which saved 34 bed-days. CONCLUSION: The fast track technology reduces the degree of surgical aggression, increases surgery safety, and decreases the number of intraoperative complications and hospital stay duration.

[The use of intraoperative neuroimaging tools and a navigation system in surgical treatment of primary and metastatic tumors of the spine].

INTRODUCTION: Surgical treatment of spinal tumors is associated with a high risk of intraoperative complications, including injury to the spinal cord, its roots, and large vessels both during tumor resection and at the stabilization stage during implantation of pedicular or corporal screws. The use of intraoperative neuroimaging tools and a navigation system in surgical treatment of oncological diseases of the spine enables identifying the location and extension of a tumor lesion directly in the operating room, which provides control of the resection area and the possibility of the spine stabilization under disturbed anatomy conditions when bone density is altered by the osteolytic process or systemic changes. Also, the risk of injury to the major blood vessels is reduced. MATERIAL AND METHODS: Surgical treatment of 156 patients with primary and metastatic tumors of the spine was performed at the Burdenko Neurosurgical Institute in the period from 2002 to December 2014. Twelve patients underwent diagnostic intervention (transcutaneous biopsy), and 35 patients underwent surgery using intraoperative CT and a navigation systems. The indication for biopsy using both CT and the navigation system was the presence of a spinal tumor not verified by a pathomorphological examination. An O-arm intraoperative computed tomography scanner and a Medtronic's StealthStation S7 Navigation System were used in all cases. CONCLUSION: The use of both CT and the navigation system provides high quality treatment and significantly reduces radiation exposure to the medical personnel and patient. The possibility of intraoperative identification of the location and extension of a tumor in bone tissue facilitates adequate tumor resection within the intact surgical margin, with the surrounding vessels and neurological structures being under real-time control.