Optimization and degradation studies of cellulose transesterification to palmitate esters in superbase ionic liquid.

Cellulose palmitates (CPs) were synthesized with varying degrees of substitution (DS) via a catalyst-free, homogeneous transesterification of cellulose in a novel superbase ionic liquid (SB-IL) system, specifically 5-methyl-1,5,7-triaza-bicyclo[4.3.0]non-6-enium acetate [mTBNH][OAc], combined with dimethyl sulfoxide (DMSO) as a co-solvent, using vinyl palmitate as the acylating agent. We examined the influence of reaction temperature, reaction time, and the molar ratio of vinyl palmitate to anhydroglucose unit (AGU) on the DS, which ranged from 0.5 to 2.3 under the given conditions. Notably, the reaction order of the three hydroxy groups was C6-OH > C2-OH > C3-OH. To elucidate the chemical structure of CPs and confirm the transesterification process, various spectroscopic techniques including 1H nuclear magnetic resonance (NMR), 13C NMR, heteronuclear single quantum correlation (HSQC), and solid-state NMR were employed. Higher reaction temperatures and extended reaction times led to a decrease in the DS of CPs, potentially due to the degradation of some of the involved chemicals during the transesterification process. We also investigated the stability of the pure ionic liquid (IL) and the IL + DMSO solvent system at elevated temperatures by heating them at 100 °C for 5 h, confirming their chemical integrity through 1H NMR analysis. Additionally, we assessed the compatibility between the solvent system and cellulose by subjecting a mixture of cellulose and the solvent system to 100 °C for 5 h. To compare the structures of untreated cellulose and regenerated cellulose, Fourier transform infrared (FT-IR) spectroscopy was employed. Furthermore, we determined the molar mass of both untreated cellulose and regenerated cellulose, as well as CPs synthesized at higher reaction temperatures and longer durations, using intrinsic viscosity measurements. Lastly, we examined the solubility properties of CPs.

Opinion research among Russian Physicians on the application of technologies using artificial intelligence in the field of medicine and health care.

BACKGROUND: To date, no opinion surveys has been conducted among Russian physicians to study their awareness about artificial intelligence. With a survey, we aimed to evaluate the attitudes of stakeholders to the usage of technologies employing AI in the field of medicine and healthcare and identify challenges and perspectives to introducing AI. METHODS: We conducted a 12-question online survey using Google Forms. The survey consisted of questions related to the recognition of AI and attitudes towards it, the direction of development of AI in medicine and the possible risks of using AI in medicine. RESULTS: 301 doctors took part in the survey. 107 (35.6%) responded that they are familiar with AI. The vast majority of participants considered AI useful in the medical field (85%). The advantage of AI was associated with the ability to analyze huge volumes of clinically relevant data in real time (79%). Respondents highlighted areas where AI would be most useful-organizational optimization (74%), biopharmaceutical research (67%), and disease diagnosis (52%). Among the possible problems when using AI, they noted the lack of flexibility and limited application on controversial issues (64% and 60% of respondents). 56% believe that AI decision making will be difficult if inadequate information is presented for analysis. A third of doctors fear that specialists with little experience took part in the development of AI, and 89% of respondents believe that doctors should participate in the development of AI for medicine and healthcare. Only 20 participants (6.6%) responded that they agree that AI can replace them at work. At the same time, 76% of respondents believe that in the future, doctors using AI will replace those who do not. CONCLUSIONS: Russian doctors are for AI in medicine. Most of the respondents believe that AI will not replace them in the future and will become a useful tool. First of all, for optimizing organizational processes, research and diagnostics of diseases. TRIAL REGISTRATION: This study was approved by the Local Ethics Committee of the Lomonosov Moscow State University Medical Research and Education Center (IRB00010587).

Rhodococcus rhodochrous IEGM 1360, an Effective Biocatalyst of C3 Oxidative Transformation of Oleanane Triterpenoids.

The optimal conditions for C3 oxidative biotransformation of 1.0 g/L pentacyclic triterpenoids oleanolic (OA) and glycyrrhetinic (GA) acids were determined using the resting cells of Rhodococcus rhodochrous IEGM 1360 from the Regional Specialised Collection of Alkanotrophic Microorganisms. Resting cell suspensions (OD600 2.6, pH 8.0, and OD600 2.2, pH 6.0) showed the highest catalytic activity against OA and GA, resulting in the formation of 61 and 100% of their 3-oxo derivatives, respectively. Using phase contrast, atomic force, and confocal laser scanning microscopy, an adaptive response of rhodococci to the effects of OA and GA was revealed. In silico, the apoptotic activity of 3-oxo-OA and antioxidant activity of 3-oxo-GA have been assumed. In vitro, a pronounced antibacterial activity of 3-oxo-OA against Micrococcus luteus, Escherichia coli, Staphylococcus aureus, and Bacillus subtilis was shown. The absence of toxic effects of the above triterpenoids and their 3-oxo derivatives on aquatic objects and plants was demonstrated in silico and in vitro, respectively. Supplementary Information: The online version contains supplementary material available at 10.1134/S0026261722603360.

[Melanotic neuroectodermal tumor of infancy. Clinical case of large fontanel tumor and literature review]. / Melanoticheskaya neiroektodermal'naya opukhol' mladentsev. Klinicheskii sluchai opukholi v oblasti bol'shogo rodnichka i obzor literatury.

Melanotic neuroectodermal tumor of infancy (MNTI) is a neonatal tumor with progressive growth and high recurrence rate. Aggressive growth and localization of tumor often lead to significant cosmetic defects of cranial and facial bones. The authors report MNTI in a 6-month-old boy with lesion of the large fontanel. Total resection was followed by recurrence after 3 weeks. Repeated resection with subsequent radiotherapy was performed. The follow-up period was 6 months after repeated resection. There was no tumor growth throughout this period. Considering this case and world experience, we can conclude that treatment strategy for MNTI is still unclear.

European Biomedical Research Infrastructures and the Fight against COVID-19 Pandemic.

The study aims to assess the role of EU biomedical research infrastructures in the fight against the COVID-19 pandemic and to analyze their response to the challenges associated with the spread of the new pathogen. Materials and Methods: We analyzed the materials of the Seventh Framework Program for Research and Technological Development (FP7, 2007-2013) of the EU and the Eighth Framework Program "Horizon 2020" (FP8, 2014-2020), official reports of the European Strategic Forum on Research Infrastructures, expert reports, as well as documents of the European Commission, the COVID-19 Data Portal, and other relevant sources of information. Results: The analysis revealed that the mechanisms created within the united European research community provided for a flexible response to the emerging threat of COVID-19 as soon as January-May 2020. In particular, information channels were established to timely analyze the research results and coordinate the efforts in the fight against COVID-19. The biomedical infrastructures created in the EU and proved successful earlier have now been mobilized to search for ways of preventing and treating COVID-19. These mechanisms facilitated communication and data exchange between various research institutions and thus laid the ground for new achievements in this area. Conclusion: The decisions taken to combat the COVID-19 pandemic have convincingly illustrated that the EU research infrastructures, integrated into a united ecosystem, are highly adaptable and flexible, which allows to realign priorities in a short time and to create instruments that enable scientists to respond to new challenges.

Calcineurin and Its Role in Synaptic Transmission.

Calcineurin (CaN) is a serine/threonine phosphatase widely expressed in different cell types and structures including neurons and synapses. The most studied role of CaN is its involvement in the functioning of postsynaptic structures of central synapses. The role of CaN in the presynaptic structures of central and peripheral synapses is less understood, although it has generated a considerable interest and is a subject of a growing number of studies. The regulatory role of CaN in synaptic vesicle endocytosis in the synapse terminals is actively studied. In recent years, new targets of CaN have been identified and its role in the regulation of enzymes and neurotransmitter secretion in peripheral neuromuscular junctions has been revealed. CaN is the only phosphatase that requires calcium and calmodulin for activation. In this review, we present details of CaN molecular structure and give a detailed description of possible mechanisms of CaN activation involving calcium, enzymes, and endogenous and exogenous inhibitors. Known and newly discovered CaN targets at pre- and postsynaptic levels are described. CaN activity in synaptic structures is discussed in terms of functional involvement of this phosphatase in synaptic transmission and neurotransmitter release.

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.

[The intestinal microbiota composition in patients with multiple sclerosis receiving different disease-modifying therapies DMT]. / Osobennosti sostava mikrobioty kishechnika u patsientov s rasseiannym sklerozom, poluchaiushchikh preparaty, izmeniaiushchie techenie rasseiannogo skleroza.

AIM: To describe characteristics of the intestinal microbiota in patients with multiple sclerosis (MS) treated with glatiramer acetate (GA) or fingolimode (FG) for understanding causal relationships between gut microbiota and autoimmune processes in MS patients. MATERIAL AND METHODS: The study included 34 patients treated with GA (n=17) or FG (n=17). GA was used in a dose of 20 mg/kg subcutaneously once a day, FG in a dose of 0.5 mg daily. All patients were examined during remission. To assess the composition of gut microbiota, bacteriological and real-time PCR techniques were used. DNA was extracted from feces using DNA-EXPRESS kit. RESULTS AND CONCLUSION: There was a decrease in numbers of Escherichia coli with normal enzymatic activity, which was replaced by atypical forms of E. coli, Enterobacter spp. and fungi of the genus Candida, and, during treatment with GA, by atypical forms of E. coli, Proteus spp., Parvimonas micra. These differences indicate the effect of the therapy on the intestinal microbiota composition.

Enterococcus faecium strain L-3 and glatiramer acetate ameliorate experimental allergic encephalomyelitis in rats by affecting different populations of immune cells.

The effect of probiotic Enterococcus faecium strain L-3 was studied in rats with experimental allergic encephalomyelitis (EAE). Glatiramer acetate (GA) was used as control drug. E. faecium strain L-3 and GA both were able to reduce the severity of EAE in a similar fashion. Both approaches increased the proportion of EAE resistant rats and rats with mild disease, prolonged the inductive phase of EAE and reduced the disease duration. Study of the phenotypes of immune cells in blood revealed the differences in immunoregulatory pathways that mediate the protective action of probiotic or GA treatment of EAE. The presence of pronounced protective and immunomodulating effects of the probiotic E. faecium strain L-3 opens an opportunity of its application for the treatment of multiple sclerosis.

[Basal ganglia germinomas in children. Four clinical cases and a literature review].

UNLABELLED: Basal ganglia germinomas are a specific group of intracranial germinomas. Their early diagnosis is complicated due to their atypical localization and diversity of neuroimaging and clinical signs. MATERIAL AND METHODS: We describe 4 cases of basal ganglia germinoma in boys of 13, 14, 15, and 16 years of age. The medical history data, clinical features, neuroimaging and histological characteristics of basal ganglia germonomas, and preliminary results of the treatment are presented. CONCLUSION: Basal ganglia germinomas are usually verified at the late stage of the disease when patients are detected with extended lesions of the basal ganglia and severe neurological and neuroendocrine deficits. This situation is due to clinical and imaging signs that are untypical of common germinomas.

[EFFECT OF PROBIOTIC ENTEROCOCCI AND GLATIRAMER ACETATE ON THE SEVERITY OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN RATS ].

Currently intestinal microbiota is considered as a potential target for influence in various pathologies which have inflammation, autoimmunity or neurodegeneration in the genesis. Multiple sclerosis (MS) combines all these processes in the pathogenesis. Furthermore, the balance of the components of intestinal microbiota is disrupted during MS and followed by disbiosis. Different probiotics - bacteria with proven beneficial properties are widely used to correct dysbisis. In this paper, was investigated the ability of probiotic strain Enterococcus faecium L-3 to reduce disease severity in multiple sclerosis model - experimental allergic encephalomyelitis (EAE). E. faecium L-3 were used alone or in combination with glatiramer acetate (GA). It is shown that administration of E. faecium L-3 reduces the severity of EAE in rats almost as same as that of GA. However, when the probiotic enterococci administered together with GA the protective effect does not observed. It is assumed that these preparations stimulates different ways of the immune system, because their action stimulate different immune cells populations. The study demonstrates the ability of E. faecium L-3 to influence on the immune system in MS, directly and indirectly (through the correction of dysbiosis). This fact allows us to consider E. faecium L-3 as a potential tool for immunomodulation in autoimmune, inflammatory and neurodegenerative diseases.

[Growing teratoma syndrome in a patient with intracranial germ cell tumor].

A six-year-old patient with non-germinomatous germ cell tumor of the chiasmatic-sellar area developed polyuria and polydipsia as the first symptoms of the disease. Then there were signs of precocious puberty and vision impairment. MRI examination revealed a shiasmatic sellar tumor and occlusive hydrocephalus. Tumor marker levels in blood serum were elevated. The alpha-fetoprotein level was increased 5-fold; human chorionic gonadotropin 20-fold. These levels increased over time. The patient received 2 cycles of PEI multiagent chemotherapy (Ifosfamide 1.5 g/m(2), Cisplatin 20 mg/m(2), Etoposide 100 mg/m(2)) during 5 days and 1 cycle of second-line multiagent chemotherapy (Cisplatin 100 mg/m(2) for 1 day and Endoxan 1500 mg/m(2) for 2 days). Despite the decrease in tumor marker levels to normal values, the patient's vision still deteriorated. MRI examination revealed that tumor size increased and its structure changed. Total tumor resection led to vision improvement and regression of intracranial hypertension. Histological analysis of tumor tissue only revealed a mature teratoma. This phenomenon, known as growing teratoma syndrome, is very rare among patients with intracranial non-germinomatous germ cell tumors.

[CHANGES IN THE QUALITATIVE AND QUANTITATIVE COMPOSITION OF GUT MICROBIOTA IN RATS DURING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS].

In this study, on the model of multiple sclerosis - experimental allergic encephalomyelitis (EAE), the dynamics of changes in the qualitative and quantitative composition of the intestinal microbiota in rats with symptoms of the disease and asymptomatic course were compared. It was found that the composition of the intestinal microbiota in rats with the clinical symptoms of EAE is shifted towards gram-negative opportunistic microorganisms of the genus Citrobacter, Prote- us, Klebsiella and enteropathogenic Escherichia coli. It has been shown that rats without clinical signs of EAE have higher levels of Faecalibacteriumprausnitzii. The significance of the complex changes in the composition of the intestinal microbiota, indicating long-lasting dysbiosis in rats during the development of EAE is discussing.

The mechanism of choline-mediated inhibition of acetylcholine release in mouse motor synapses.

The mechanism of action of tonically applied choline, the agonist of α7 nicotinic acetylcholine receptors (nAChRs), to the spontaneous and evoked release of a neurotransmitter in mouse motor synapses in diaphragm neuromuscular preparations using intracellular microelectrode recordings of miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs) was studied. Exogenous choline was shown to exhibit a presynaptic inhibitory effect on the amplitude and quantal content of EPPs for the activity of neuromuscular junction evoked by single and rhythmic stimuli. This effect was inhibited either by antagonists of α7-nAChRs, such as methyllycaconitine and α-cobratoxin, or by blocking SK-type calcium-activated potassium (KCa) channels with apamin or blocking intraterminal ryanodine receptors with ryanodine. A hypothesis was put forward that choline in mouse motoneuron nerve terminals can activate presynaptic α7-nAChRs, followed by the release of the stored calcium through ryanodine receptors and activation of SK-type KCa channels, resulting in sustained decay of the quantal content of the evoked neurotransmitter release.

[Characteristics of medulloblastoma in children under age of three years].

We present a series of 51 medulloblastoma in children under three years, collected in N.N. Burdenko Neurosurgical Institute from 2000 to 2010. 57% of the tumors showed desmoplastic/nodular histology. Performed fluorescence in situ hybridization (FISH) analysis revealed the MYC oncogene amplification in 4%, the MYCN oncogene amplification - in 8%, isochromosome 17q - in 16% of cases. 9q deletion was found in 8% of desmoplastic/ nodular medulloblastomas. Our results showed that desmoplastic/nodular medulloblastoma has a positive predictive value for progression-free survival. Another feature of a biology of medulloblastomas in children younger than three years is the lack of nuclear accumulation of beta-catenin, and 6q deletion. Medulloblastomas with MYCN oncogene amplification often exhibit desmoplastic/nodular histology and a relatively favorable outcome. The most unfavorable prognostic marker is the MYC oncogene amplification, which in our series of 100% combined with the large cell/anaplastic medulloblastoma and isochromosome 17q - such tumors should be included in the "high risk" protocol.

[Glioneuronal tumor with neuropil-like islands in a neonate]. / Glioneironal'naia opukhol' s uchastkami neiropilia u rebenka grudnogo vozrasta.

Glioneuronal tumor with neuropil-like islands - GTNI is a rare histopatological subtype of anaplastic astrocytoma. English-language literature contains only 43 observations, among them only 4 observations in children up to 18 years. Neuropil is an eosinophilic stained a cellular foci of tumor tissue. These cells demonstrate less proliferation activity than prevailing glial component, which is characterized by a high degree of atypia - Gr III according to WHO classification. Single reports about verification of the glioneuronal tumor with neuropil-like islands in children are supplemented with an observation of the case with tumor, located in lateral ventricular in infant with the onset of hypertension symptoms at the age of 11 months. The potential for complete removal of these tumors despite its large size and young age of the child is presented. However, the prognosis in infants with GTNI despite completeness of removal and chemotherapy might be extremely unfavorable - in case of intraventricular localization progression in the form of tumor implantation on ventricular ependyma is possible.

[Investigation of the genetic profile of Blastocystis species in Saint Petersburg residents with gastrointestinal tract diseases in different age groups].

A total of 1500 people, including 1273 children with various gastrointestinal tract diseases and 327 patients with chronic viral hepatitis C, were examined. Microscopy and polymerase chain reaction (PCR) were used to determine Blastocystis in the feces. Blastocysts were detected in 33% of the patients with chronic viral hepatitis C and in 4.9% of the children. Genotyping established that Blastocystis species subtype 3 (antroponous) was encountered relatively rarely (25%) in these patients; there were most common Blastocystis species subtypes 5 (36.1%) and 6 (36.1%). Significant intestinal dyspepsia was noted in all the patients with chronic hepatitis C and Blastocystis invasion. Blastocystis species subtype 3 was prevalent (62.3%) among the examined children. The other subtypes were less frequently detected. These were subtype 1 (29.5%), subtype 2 (24.3%), subtype 4 (1.3%), and subtype 7 (3.8%) whereas subtype 5 and subtype 6 were not found in any case. The comparison of clinical symptoms in children could reveal the following tendency: there were digestive disorders and skin allergic reactions with Blastocystis species subtype 1 and subtype 2, respectively.

[The influence of GPIIIA gene polymorphism on the variability of standard electrocardiogram in patients with acute coronary syndrome].

The authors analyse effect of GPIIIA gene (PI a allele) polymorphism on the frequency of complicated coronary heart disease in patients with dyslipidemia and hypertensive disease. Specific features of ventricular repolarization (T-wave variability) in patients with acute coronary syndrome are described.

[The levels of stable organic pollutants in the breast milk of women living in the Irkutsk region].

The concentrations of stable organic chlorine pollutants (SOCP) in the breast milk of women living in Irkutsk, Baikalsk, and the settlement of Kachug are lower than those in the increased SOCP-burdened areas of the Irkutsk Region (the town of Usolye-Sibirskoye, settlements on the shore of the Baikal Lake) and comparable with those in Russia and industrially developed countries of the world. The content of SOPC is much lower than those in the developing countries where this pesticide continues to be applied. The breast milk levels of OCP, TEQ (polychlorinated dibento-para-dioxines and polychlorinated dibenzofurans) in all towns and individual indicator polychlorinated biphenyls (PCB) in Irkutsk significantly decreased as compared with those in the 1980s. However, in Kachug and Baikalsk, the concentrations of PCB practically unchanged and the level of some congeners increased. The absence of changes in the content of PCB in Kachug and Baikalsk may be associated with no decrease in environmental pollution in the Irkutsk Region. Altered breast concentrations of SOCPs caused a reduction in their intake in babies.

2-(4-Chloro-benzo-yl)-1-(diamino-methyl-ene)hydrazinium chloride monohydrate.

In the cation of the title compound, C(8)H(10)ClN(4)O(+)·Cl(-)·H(2)O, the guanidinium group is planar (maximum deviation = 0.0001 Å) and nearly perpendicular to carboxamide group, making a dihedral angle of 87.0 (3)°. The N atoms of the guanidine fragment have a planar trigonal configuration and the N atom of the carboxamide group adopts a pyramidal configuration. In the crystal structure, inter-molecular N-H⋯O, N-H⋯Cl and O-H⋯Cl hydrogen bonds link the cations, anions and water mol-ecules into layers parallel to the bc plane.