Position statement: Recommendations on the diagnosis and treatment of Malassezia folliculitis.

Malassezia is a lipophilic yeast that is a part of the human mycobiome. Malassezia folliculitis appears when the benign colonization of the hair follicles, by the Malassezia yeasts, becomes symptomatic with pruritic papules and pustules. Although Malassezia folliculitis is common in hospital departments, diagnosing and treating it varies among dermatologists and countries. The European Academy of Dermatology and Venereology Mycology Task Force Malassezia folliculitis working group has, therefore, sought to develop these recommendations for the diagnosis and management of Malassezia folliculitis. Recommendations comprise methods for diagnosing Malassezia folliculitis, required positive findings before starting therapies and specific treatment algorithms for individuals who are immunocompetent, immunocompromised or who have compromised liver function. In conclusion, this study provides a clinical strategy for diagnosing and managing Malassezia folliculitis.

[Interaction of DNA Methyltransferase Dnmt3a with Phosphorus Analogs of S-Adenosylmethionine and S-Adenosylhomocysteine].

Enzymatic methyltransferase reactions are of crucial importance for cell metabolism. S-Adenosyl-L-methionine (AdoMet) is a main donor of the methyl group. DNA, RNA, proteins, and low-molecular-weight compounds are substrates of methyltransferases. In mammals, DNA methyltransferase Dnmt3a de novo methylates the C5 position of cytosine residues in CpG sequences in DNA. The methylation pattern is one of the factors that determine the epigenetic regulation of gene expression. Here, interactions with the catalytic domain of Dnmt3a was for the first time studied for phosphonous and phosphonic analogs of AdoMet and S-adenosyl-L-homocysteine (AdoHcy), in which the carboxyl group was substituted for respective phosphorus-containing group. These AdoMet analogs were shown to be substrates of Dnmt3a, and the methylation efficiency was only halved as compared with that of natural AdoMet. Both phosphorus-containing analogs of AdoHcy, which is a natural methyltransferase inhibitor, showed similar inhibitory activities toward Dnmt3a and were approximately four times less active than AdoHcy. The finding that the phosphonous and phosphonic analogs are similar in activity was quite unexpected because the geometry and charge of their phosphorus-containing groups differ substantially. The phosphorus-containing analogs of AdoMet and AdoHcy are discussed as promising tools for investigation of methyltransferases.

Experimental and Model Study of a Swirling Fluid Flow in a Converging Channel As a Simulation of Blood Flow in the Heart and Aorta.

Study of swirling flows in channels corresponding to the static approximation of flow channels of the heart and major vessels with a longitudinal-radial profile zR2 = const and a concave streamlined surface at the beginning of the longitudinal coordinate has been carried out. A comparative analysis of the flow structure in channel configurations zRN = const, where N = -1, 1, 2, 3, in the absence and presence of a concave surface was carried out. The numerical modeling was compared with the results of hydrodynamic experiments on the flow characteristics and the shape of the flow lines. The numerical model was used to determine the velocity structure, viscous friction losses, and shear stresses. Numerical modeling of steady-state flows for channels without a concave surface showed that in the channel zR2 = const there is a stable vortex flow structure with the lowest viscous friction losses. The presence of a concave surface of sufficient size significantly reduces viscous friction losses and shear stresses in both the steady state and pulsed modes.

Entrainment, stopping, and transmission of microwave solitons of self-induced transparency in counter-propagating magnetized electron beam.

Based on numerical simulations of a boundary problem, we study various scenarios of microwave soliton formation in the process of cyclotron resonance interaction of a short electromagnetic pulse with a counter-propagating initially rectilinear electron beam taking into account the relativistic dependence of the cyclotron frequency on the electrons' energy. When a certain threshold in the pulse energy is exceeded, the incident pulse can propagate without damping in the absorbing beam, similar to the effect of self-induced transparency in optics. However, mutual motion of the wave and electrons can lead to some novel effects. For relatively small energy of the incident pulse, the microwave soliton is entrained by the electron beam opposite to the direction of the wave's group velocity. With an increase in the pulse energy, soliton stopping occurs. This regime is characterized by the close-to-zero pulse velocity and can be interpreted as a variety of the "light stopping." High-energy microwave solitons propagate in the direction of the unperturbed group velocity. Their amplitude may exceed the amplitude of the incident pulse, i.e., nonlinear self-compression takes place. A further increase in the incident energy leads to the formation of additional high-order solitons whose behavior is similar to that of the first-order ones. The characteristics of each soliton (its amplitude and duration) correspond to analytical two-parametric soliton solutions that are to be found from consideration of the unbounded problem.

[A systematic review of radiotherapy for primary renal cell carcinoma].

Renal cell cancer accounts for 2% of all cancers. The gold standard for managing patients with no evidence of distant metastasis renal cell cancer remains is complete surgical resection. The clinical data investigating preoperative radiotherapy failed to reveal benefited from this methods. The role of routine postoperative radiotherapy in the management of renal cell cancer is not established in patients with localized disease after complete surgical resection. Renal cell cancer is radioresistant tumor for conventional radiation therapy. Although renal cell carcinoma is related to radioresistant tumors, in recent years new promising directions in radiation therapy have become apparent. To overcome the radioresistance of renal cell carcinoma, the use of modified radiation therapy regimens with high doses per fraction is justified. new technologies of radiation therapy, which include stereotactic radiation therapy allows to accurately deliver doses of ionizing radiation to a tumor, without the risk of damage to neighboring tissues and organs. Recent data showing that with the use of high-precision methods, such as SBRT, unresectable local renal cell carcinoma can successfully be treated with durable local control and low toxicity. Nonetheless, prospective, randomized trials and omparative effectiveness studies are needed to further evaluate this ablative modality in the treatment of renal cell carcinoma.

[Etiopathophysiological mechanism of systemic and local allergic sensitization in the development of chronic rhinitis and chronic rhinosinusitis]. / Etiopatofiziologicheskii mekhanizm obshchei i mestnoi allergicheskoi sensibilizatsii v razvitii khronicheskogo rinita i khronicheskogo rinosinusita.

The persistence, development and exacerbation of chronic rhinitis and chronic rhinosinusitis all involve sensitization to respiratory allergens. The allergic response in question is the IgE-mediated mechanism of rhinitis, which often leads to a complex of etiopathophysiological malfunctions in various organs and systems. For clinical classification and further management of patients, it is important not to miss the detection of both systemic allergic sensitization to aeroallergens (which is achieved by conducting skin prick test or detecting the allergen-specific immunoglobulin E in the blood) and local sensitization (which can be confirmed by conducting nasal provocation test or detecting the nasal-specific immunoglobulin E in nasal mucosa). Before a full examination is conducted and both systemic and local sensitization are ruled out, the diagnosis of non-allergic rhinitis and the management of a patient with non-allergic nasal inflammation may be premature.

Involvement of NMDA and GABA(A) receptors in modulation of spontaneous activity in hippocampal culture: Interrelations between burst firing and intracellular calcium signal.

Spontaneous burst firing is a hallmark attributed to the neuronal network activity. It is known to be accompanied by intracellular calcium [Са2+]i oscillations within the bursting neurons. Studying mechanisms underlying regulation of burst firing is highly relevant, since impairment in neuronal bursting accompanies different neurological disorders. In the present study, the contribution of NMDA and GABA(A) receptors to the shape formation of spontaneous burst -was studied in cultured hippocampal neurons. A combination of inhibitory analysis with simultaneous registration of neuronal bursting by whole-cell patch clamp and calcium imaging was used to assess spontaneous burst firing and [Са2+]i level. Using bicuculline and D-AP5 we showed that GABA(A) and NMDA receptors effectively modulate burst plateau phase and [Са2+]i transient spike which can further affect action potential (AP) amplitudes and firing frequency within a burst. Bicuculline significantly elevated the amplitude and reduced the duration of both burst plateau phase and [Са2+]i spike resulting in an increase of AP firing frequency and shortening of AP amplitudes within a burst. D-AP5 significantly decreases the amplitude of both plateau phase and [Са2+]i spike along with a burst duration that correlated with an increase in AP amplitudes and reduced firing frequency within a burst. The effect of bicuculline was occluded by co-addition of D-AP5 revealing modulatory role of GABA(A) receptors to the NMDA receptor-mediated formation of the burst. Our results provide new evidence on importance of NMDA and GABA(A) receptors in shaping burst firing and Ca2+transient spikes in cultured hippocampal neurons.

Emerging antifungal treatment failure of dermatophytosis in Europe: take care or it may become endemic.

BACKGROUND: Dermatophytosis is a world-wide distributed common infection. Antifungal drug resistance in dermatophytosis used to be rare, but unfortunately the current Indian epidemic of atypical widespread recalcitrant and terbinafine-resistant dermatophytosis is spreading and has sporadically been reported in Europe. OBJECTIVES: To explore the occurrence of clinical and mycological proven antifungal drug resistance in dermatophytes in Europe. METHODS: A standardized questionnaire was distributed through the EADV Task Force of Mycology network to dermatologists in Europe. RESULTS: Representatives from 20 countries completed the questionnaires of which 17 (85 %) had observed clinical and/or mycological confirmed antifungal resistance, two countries published cases of antifungal resistance and one country had no known cases. CONCLUSIONS: This pilot study confirms that both clinical and mycological antifungal resistance exist in Europe.

The Effect of Mechanical Compatibility and of Thrombogenicity on the Ingrowth of a New Synthetic Vascular Prosthesis (Experimental Study).

Common disadvantages of modern synthetic vascular prostheses are thrombogenicity and lack of biomechanical compatibility with the prothesized vessel. To elucidate the role of these factors in the prosthesis integration, prostheses specimens were made by the electrospinning from the known materials: polycaprolactone, polyurethane and a mixture of fluorine-containing synthetic rubber FKM-26 with fluoroplastic F-26. The germination of the prostheses was compared with standard e-PTFE prosthesis in the pigs infrarenal aorta. The elastic properties of prostheses were studied by elastometry under the physiological range of loads. The thrombogenicity of the materials was determined by the number of platelets adhered to material surface exposed to native blood. The patency of the prostheses was checked by aortography. The germination of prostheses was assessed in the histological examination. It was shown that, with this set of materials, biomechanical compatibility turned out to be a more important factor of integration than the material thrombogenicity.

[Long-term results of radical surgery treatment of patients with bladder cancer].

PURPOSE: To investigate long-term results after radical cystectomy in patients with bladder cancer. MATERIALS AND METHODS: Since 1997 to 2020 yy. we have performed 404 radical cystectomy with different methods of derivation for patients with bladder cancer in our clinic. There were 342 (86,4%) men and 62 (13,6%) women. Laboratory study, ultrasound, X-ray, CT. MRI investigations were performed in all patients. RESULTS: Mortality rate was 2,9%. Early and late postoperative complications have occurred in 136 (33,6%) and 98 (41,8%) cases, respectively. Local recurrence has occurred in 33 (8,5%) patients. 10-years overall and cancer-specific survival were 43,4% and 47,2%, respectively. In lymph-negative patients 2-years and 5-years overall survival were 81,2% and 67,2%, respectively. In lymph positive patients 2-years and 5-years overall survival were 46,9% and 13,9%, respectively. In lymph-negative patients 2-years and 5-years cancer-specific survival were 83,6% and 70,7%, respectively. In lymph positive patients 2-years and 5-years cancer-specific survival were 51,0% and 15,1%, respectively. Overall and cancer -specific survival decreased according to increasing pT-stage and histopathologic grade. CONCLUSIONS: pT-stage (pT), lymp nodes status (pN), histopathologic grade ( pG) have a significant independent influence on overall and cancer-specific survival of bladder cancer patients after radical cystectomy.

[SCREENING ASSESSMENT OF MATERIALS THROMBOGENICITY BY THE NUMBER OF PLATELETS ADHERED FROM THE FLOWING NATIVE BLOOD].

The materials used in the construction of implants contacting with blood should be resistant to thrombus formation. One of the stages of a thrombogenicity assessment of materials is to determine the number of platelets adhered to its surface during the exposure to flowing blood under ex viAvo conditions. The aim of this study was to develop a modified test for screening assessment of materials for their thrombogenicity in contact with native blood. For the purpose of the study, flow chambers of were developed, allowing to mountain simultaneously 16 material samples. The chamber was connected to the circulatory system of the experimental animal through arterial and venous ports in such a way that blood, passing through the chamber, returned to the animal. The exposure time was 1 min. After perfusion the samples were rinsed and stained. The number of platelets adhered per unit area was calculated automatically that allowed significant error diminution. A total of 9 experiments were carried out on pigs under ex vivo conditions. The method was validated using standard samples of pyrolytic carbon, VT-6 titanium, glass, and polytetrafluorethylene as reference materials. New materials for synthetic vascular prostheses have been investigated. The developed technique makes it possible to study the thrombogenicity of polymeric materials with sufficient reliability.

[Phylogeography and Mitochondrial Polymorphism of Asian Coho Salmon].

Multiple Pleistocene glaciations significantly affected the gene pool of many species inhabiting the Northern part of the Pacific Rim, an area with a rich glacial history. This paper is devoted to the study of intraspecific polymorphism of the coho salmon and the routes of its settlement throughout the Asian part of its range. Such problems are traditionally solved by comparing parts of the mitochondrial genome. Here, two fragments of mtDNA, the control region (D-loop) and the cytochrome b gene (cytb), were investigated. It was shown that the settlement of the Asian Pacific coast by the coho salmon was preceded by a chain of successive migration events from the refugium located on the North American continent to the South of the ice sheet covering the area of modern Canada and southern Alaska. The low level of genetic polymorphism in Asian coho populations seems to be a result of a pronounced founder effect, rather than being characteristic of the species as a whole.

The Effect of Antitumor Antibiotic Olivomycin A and Its New Semi-synthetic Derivative Olivamide on the Activity of Murine DNA Methyltransferase Dnmt3a.

Olivomycin A is a highly active antitumor drug that belongs to the family of aureolic acid antibiotics. The antitumor effect of olivomycin A is related to its ability to bind to the DNA minor groove in GC-rich regions as Mg2+-coordinated complexes. Characterization of cellular targets of olivomycin A and its mechanism of action is crucial for the successful application of this antibiotic in clinical practice and development of semi-synthetic derivatives with improved pharmacological properties. Previously, we have shown that minor groove ligands are able to disrupt the key epigenetic process of DNA methylation. In this paper, we have studied the impact of olivomycin A and its improved semi-synthetic analogue N,N-dimethylaminoethylamide of 1'-des-(2,3-dihydroxy-n-butyroyl)-1'-carboxy-olivomycin A (olivamide) on the functioning of de novo DNA methyltransferase Dnmt3a (enzyme that carries out methylation of cytosine residues in the DNA CG-sites in eukaryotic cells) using an in vitro system consisting of the murine Dnmt3a catalytic domain and a 30-mer DNA duplex containing four consecutive GC pairs. We have shown that olivomycin A and olivamide inhibit Dnmt3a with IC50 of 6 ± 1 and 7.1 ± 0.7 µM, respectively. Neither olivomycin A nor olivamide interfered with the formation of the specific enzyme-substrate complex; however, olivomycin A prevented formation of the covalent DNA-Dnmt3a intermediate that is necessary for the methylation reaction to proceed. The inhibitory effects of olivomycin A and olivamide can be explained by the disruption of the enzyme catalytic loop movement through the DNA minor groove (the reaction stage that precedes the covalent bond formation between DNA and the enzyme). The results of this work indicate the epigenetic contribution to the antitumor effect of aureolic acid group antibiotics.

A survey among dermatologists: diagnostics of superficial fungal infections - what is used and what is needed to initiate therapy and assess efficacy?

BACKGROUND: Superficial fungal infections are common. It is important to confirm the clinical diagnosis by mycological laboratory methods before initiating systemic antifungal treatment, especially as antifungal sensitivity and in vitro susceptibility may differ between different genera and species. For many years, the gold standard for diagnosis of superficial fungal infections has been direct fungal detection in the clinical specimen (microscopy) supplemented by culturing. Lately, newer molecular based methods for fungal identification have been developed. OBJECTIVE: This study was initiated to focus on the current usage of mycological diagnostics for superficial fungal infections by dermatologists. It was designed to investigate whether it was necessary to differentiate between initial diagnostic tests and those used at treatment follow-up in specific superficial fungal infections. METHODS: An online questionnaire was distributed among members of the EADV mycology Task Force and other dermatologists with a special interest in mycology and nail disease. RESULTS: The survey was distributed to 62 dermatologists of whom 38 (61%) completed the whole survey, 7 (11%) partially completed and 17 (27%) did not respond. Nearly, all respondents (82-100%) said that ideally they would use the result of direct microscopy (or histology) combined with a genus/species directed treatment of onychomycosis, dermatophytosis, Candida- and Malassezia-related infections. The majority of the dermatologists used a combination of clinical assessment and direct microscopy for treatment assessment and the viability of the fungus was considered more important at this visit than when initiating the treatment. Molecular based methods were not available for all responders. CONCLUSION: The available diagnostic methods are heterogeneous and their usage differs between different practices as well as between countries. The survey confirmed that dermatologists find it important to make a mycological diagnosis, particularly prior to starting oral antifungal treatment in order to confirm the diagnose and target the therapy according to genus and species.

[The intraoperative prophylaxis of local ischemical brain damage in neurosurgical patients with cerebral aneurysm]. / Intraoperatsionnaia profilaktika lokal'nogo ishemicheskogo povrezhdeniia golovnogo mozga u neirokhirurgicheskikh patsientov s tserebral'noi anevrizmoi.

AIM: To study the effectiveness of intraoperative administration of Cytoflavine for the prevention of ischemic brain injury during cerebral aneurysm (CA) clipping with temporary occlusion of the leading artery under general anesthesia. MATERIAL AND METHODS: The prospective cohort single-center study included 40 patients with CA ( the main group - 27 patients with intraoperative administration of cytoflavine; the comparison group -13 patients without use of cytoflavine), who underwent aneurism clipping with temporary occlusion of the afferent artery. We assesed the intraoperative state of the brain, the time of awakening and extubation of patients after surgery, neurological deficit and local ischemic changes in the area of surgery according to the CT of the brain in the early postoperative period, resuscitation bed-day and the relationship of these indicators with the duration of temporary occlusion of the afferent artery in the selected groups of patients. RESULTS: In intergroup comparison, patients of the main group treated with intraoperative cytoflavin showed a reduction in the time of awakening (p=0.013) and the time of extubation (p=0.01) both with temporary occlusion of the afferent artery and in patients without temporary occlusion (p<0.05). The duration of resuscitation bed-day decreased in the main group of patients receiving intraoperatively cytoflavine (p=0.01), as well as in patients in the comparison group without temporary occlusion (p<0.05). CONCLUSION: Temporary occlusion of the afferent artery with short intervals of vessel occlusion in combination with intraoperative intravenous administration of cytoflavine expands the tolerability to artery occlusion in patients operated in the 'cold' period, reduces the possibility of neurological deficit, reduces the recovery period and resuscitation bed-day after surgical clipping CA.

[Detection of DNA Methylation by Dnmt3a Methyltransferase using Methyl-Dependent Restriction Endonucleases].

DNA methylation at cytosine residues in CpG sites by DNA methyltransferases (MTases) is associated with various cell processes. Eukaryotic MTase Dnmt3a is the key enzyme that establishes the de novo methylation pattern. A new in vitro assay for DNA methylation by murine MTase Dnmt3a was developed using methyl-dependent restriction endonucleases (MD-REs), which specifically cleave methylated DNA. The Dnmt3a catalytic domain (Dnmt3a-CD) was used together with KroI and PcsI MD-REs. The assay consists in consecutive methylation and cleavage of fluorescently labeled DNA substrates, then the reaction products are visualized in polyacrylamide gel to determine the DNA methylation efficiency. Each MD-RE was tested with various substrates, including partly methylated ones. PcsI was identified as an optimal MD-RE. PcsI recognizes two methylated CpG sites located 7 bp apart, the distance roughly corresponding to the distance between the active centers of the Dnmt3a-CD tetramer. An optimal substrate was designed to contain two methylated cytosine residues and two target cytosines in the orientation suitable for methylation by Dnmt3a-CD. The assay is reliable, simple, and inexpensive and, unlike conventional methods, does not require radioactive compounds. The assay may be used to assess the effectiveness of Dnmt3a inhibitors as potential therapeutic agents and to investigate the features of the Dnmt3a-CD function.

[Endovascular Treatment of Critical Аоrtic Stenosis: Current State of the Problem and Perspectives].

The article contains the review of current understanding of the etiology and pathogenesis of degenerative aortic stenosis, approaches to surgical treatment depending on various factors, e. g. severity of defect and comorbidity, description of endovascular techniques (balloon valvuloplasty and transcatheter aortic valve implantation), and features of the selection of patients for these procedures. The authors also present assessment of results of operations performed from 2011 to 2016 in the city hospital № 2 in Saint-Petersburg. They analyze data from 72 high-risk aortic stenosis patients aged 81±6 years treated with transcatheter aortic valve implantation. In 68 out of 72 patients (94.4 %) clinical improvement was achieved with reduction of dilation of left ventricular cavity, decrease of functional class of heart failure, and decrease of mean pressure gradient across the aortic valve. A conclusion is made that these results confirm advantages and perspectives of the use of endovascular methods of treatment in this complicated group of patients.

Generation of Rogue Waves in Gyrotrons Operating in the Regime of Developed Turbulence.

Within the framework of the average approach and direct 3D PIC (particle-in-cell) simulations, we demonstrate that the gyrotrons operating in the regime of developed turbulence can sporadically emit "giant" spikes with intensities a factor of 100-150 greater than the average radiation power and a factor of 6-9 exceeding the power of the driving electron beams. Together with the statistical features such as a long-tail probability distribution, this allows the interpretation of generated spikes as microwave rogue waves. The mechanism of spikes formation is related to the simultaneous cyclotron interaction of a gyrating electron beam with forward and backward waves near the waveguide cutoff frequency as well as with the longitudinal deceleration of electrons.

Cowpox in a human, Russia, 2015.

We investigated the first laboratory-confirmed human case of cowpox virus infection in Russia since 1991. Phylogenetic studies of haemagglutinin, TNF-α receptor-like protein and thymidine kinase regions showed significant differences with known orthopoxviruses, including unique amino-acid substitutions and deletions. The described cowpox virus strain, taking into account differences, is genetically closely related to strains isolated years ago in the same geographical region (European part of Russia and Finland), which suggests circulation of viral strains with common origin in wild rodents without spread over long distances and appearance in other parts of the world.

[Emotional impairments and their correction in patients with migraine]. / Émotsional'nye narusheniia i ikh korrektsiia u patsientov s migren'iu.

AIM: To study emotional impairments in patients with migraine and to evaluate the efficiency of Noophen therapy for this pathology. SUBJECTS AND METHODS: 63 patients aged 18 to 45 years with migraine without aura were examined. 56 patients used prophylactic antimigraine therapy: Group 1 (n = 26) received metoprolol and Group 2 took metoprolol in combination with Noophen. RESULTS: The patients with migraine had a significantly higher level of alexithymia than the controls. Concomitant anxiety disorders were found in 47 (74.6%) cases. The study provided evidence that the treatment was highly effective in Group 2 that exhibited a more pronounced decrease in pain intensity, a greater reduction in the levels of anxiety, and more vital activity. CONCLUSION: The results of this study allow a conclusion that emotional impairments are implicated in the pathogenesis and clinical presentations of migraine and that it is appropriate to use Noophen for the treatment of this pathology.