Proinflammatory status of oral fluid in COVID-19

At present, a search for promising ways to diagnose infection caused by SARS-CoV-2 is quite relevant. Oral fluid is not commonly used for assessment of COVID-19 risk. Its molecular profile reflects both local state of the oral cavity, and individual organs and systems, thus suggesting a reliable diagnostic platform. Systemic inflammatory response is known to play a crucial role in development of the coronavirus infection; the “cytokine storm” determines severity of the disease. The saliva-based diagnostics of clinical course in COVID-19 patients includes determination of IL-6, IL-8, C-reactive protein in oral fluid, in order to assess severity of the inflammatory process. The present study was carried out at the Department of Fundamental and Clinical Biochemistry with Laboratory Diagnostics, and Department of Pediatric Infections at the Samara State Medical University. The study involved 122 persons: 67 clinically healthy individuals comprised the control group, and the group of comparison included 55 inpatients with moderate or severe coronavirus infection (COVID-19) caused by SARS-CoV-2 virus as confirmed by PCR and/or ELISA testing. Development of the disease was accompanied by drastically increased contents of IL-6 and IL-8 in oral fluid of the patients relative to the indexes in healthy persons, i.e., several-fold for IL-6 (+ 650%) and even higher elevation of IL-8 levels (+ 26513%), as well as a 2-fold increase of C-reactive protein (+115%). When comparing the immune indexes of oral fluid in presence versus absence of respiratory insufficiency, a significant difference was found for salivary IL-6 (+173%) in the patients with grade 1-2 respiratory insufficiency as compared with patients free of respiratory disorders. Determination of these proinflammatory markers in patients with COVID-19 is of important prognostic significance when assessing development of the disease and its severity. Direct detection of their content in the oral fluid makes this method relevant, and potentially demanded for the outpatient diagnostics, being highly important during pandemics of coronavirus infection and limited medical resources. Examination of oral fluid at the pre-hospital stage is a resource-saving technology, since it does not require additional medical staff to take biomaterial, is non-invasive to the patient, and suggesting a wide range of research items, it can resolve a number of diagnostic issues, e.c., presence of specific genetic material or antibodies to SARS-CoV-2, severity of the inflammatory process and the risk of respiratory failure in the patient

Development of ELISA test for the quality control of Pseudomonas aeruginosa recombinant vaccine based on the hybrid recombinant protein

A hybrid recombinant protein containing the amino  acid sequences of the three  most significant Pseudomonas aeruginosa antigens  (membrane proteins OprF, OprI  and toxoid  aTox)  was incorporated into a vaccine against Pseudomonas infection. Quality control of a hybrid recombinant protein and appropriate vaccine includes  determination of authentity and completeness of adsorption upon aluminum hydroxide adjuvant. The aim of our study was to develop  techniques of quality  control for a vaccine  based on the hybrid  OprF-aToxOprI  recombinant protein specific  to  P. aeruginosa.  Hybridomas secreting  specific  monoclonal antibodies for OprF-aTox-OprI were derived  from the fusion of myeloma cells and murine spleen  cells immunized with recombinant proteins P. aeruginosa. To  produce sufficient  quantities of antibodies, the  hybrid  cells were in vivo cultured in BALB/c mice.  Supernates and ascite liquids were chromatographically purified  with immune sorbent. Conjugation of antibodies with  horseradish peroxidase was carried  out  according to  P.K.Nakane. The  hybrid  OprF-aTox-OprI recombinant protein was detected by the  solid-phase ELISA, using a panel  of monoclonal antibodies and  conjugates of monoclonal antibodies with  horseradish peroxidase. Monoclonal antibodies were specific for different  OprF-aTox-OprI epitopes. Titration assays containing OprF-aTox-OprI protein at 78 ng/ml to 5000 ng/ml were used as quantitative standards for calibration curves.To identify  the recombinant protein OprF-aTox-OprI, 55 variants  of of MAb pairs were tested.  Limits  of quantitative detection served  for selection of most  sensitive  and  specific  ELISA  variants.  The  quantitative detection limit was calculated for all 11 ELISA  variants.  Two ELISA  variants  with the highest  sensitivity were selected  for  quality  control of the  hybrid  recombinant protein. The  limits  of quantitative detection were, respectively, 2.9 and 13.6 ng/ml (0.0058  and 0.027% of the estimated antigen  content in the vaccine)  for the first and  second  ELISA  variants.  The  first variant  included a pair  of monoclonal antibodies specific  for the OprF  and OprI  epitopes, the second  variant  represented aTox and OprI  epitopes. Two variants  of ELISA  were developed to detect  the hybrid recombinant OprF-aTox-OprI protein. The first variant allows to determine the protein amount and to evaluate completeness of its adsorption on aluminum hydroxide. To confirm authenticity of the protein, both methods must be used, since they can detect all three antigens (OprF, aTox and OprI) which are present  in the fusion protein

Application of “Polyana Kvasova” Mineral Water in the Complex Therapy of Patients with Gastro-esophageal Reflux Disease and Osteochondrosis of the Spine

Aim: To investigate the effectiveness of complex therapy using “Polyana Kvasova” mineral water in patients with GERD and osteochondrosis (OH) of the cervical and thoracic spine. Materials and Methods: The examined patients included 56 Helicobacter pylori (HP)-positive patients with GERD and OH of the cervical and thoracic spine. The examined patients were divided into 2 groups depending on the scheme of complex treatment. All HP-positive patients with GERD and OH underwent standard triple anti-helicobacter therapy and itopride hydrochloride. Group I patients (n=26) received only the above-mentioned regimen. Patients of the II group (n=30) were additionally prescribed 100-150 ml of “Polyana Kvasova” carbonated bicarbonate-sodium mineral water (MW) as a natural antacid, warm, still 4 times a day (1.5 hours before meals and after 45 minutes after – both in the morning and evening) within 1 month. Results: The complex therapy carried out had a positive effect on the endoscopic picture of GERD in patients with cervical and thoracic OH. The decrease in the severity of RE was accompanied by an increase in the number of GERD patients in whom the erosive form of reflux esophagitis was not detected during repeated fibroesophagogastroduodenoscopy (FEGDS) (mainly in the II group of examined patients – 10.0% of patients, p<0.05). The additional prescription of “Polyana Kvasova” MW to the complex treatment increased the frequency of eradication of HP infection by 9.2% – p<0.05 at the background of more pronounced normalization of clinical and endoscopic signs of GERD. Conclusions: 1. GERD is often manifested by atypical extraesophageal symptoms (up to 25.0-27.3% of cases) in patients with OH of the cervical and thoracic spine. 2. The use of standard triple AHT in combination with itopride hydrochloride is an effective method of correcting esophageal and extraesophageal clinical manifestations of GERD in patients with cervical and thoracic spine OH. 3. The additional prescription of “Polyana Kvasova” MW as part of the complex therapy of patients with GERD and OH of the cervical and thoracic regions is a safe, effective method for reducing clinical symptoms, the severity of esophageal lesions with repeated FEGD, and also contributes to increasing the frequency of HP infection eradication in the data patients

Diffuse-Charge Dynamics in Electrochemical Systems

The response of a model micro-electrochemical system to a time-dependent applied voltage is analyzed. The article begins with a fresh historical review including electrochemistry, colloidal science, and microfluidics. The model problem consists of a symmetric binary electrolyte between parallel-plate, blocking electrodes which suddenly apply a voltage. Compact Stern layers on the electrodes are also taken into account. The Nernst-Planck-Poisson equations are first linearized and solved by Laplace transforms for small voltages, and numerical solutions are obtained for large voltages. The ``weakly nonlinear'' limit of thin double layers is then analyzed by matched asymptotic expansions in the small parameter $\epsilon = \lambda_D/L$, where $\lambda_D$ is the screening length and $L$ the electrode separation. At leading order, the system initially behaves like an RC circuit with a response time of $\lambda_D L / D$ (not $\lambda_D^2/D$), where $D$ is the ionic diffusivity, but nonlinearity violates this common picture and introduce multiple time scales. The charging process slows down, and neutral-salt adsorption by the diffuse part of the double layer couples to bulk diffusion at the time scale, $L^2/D$. In the ``strongly nonlinear'' regime (controlled by a dimensionless parameter resembling the Dukhin number), this effect produces bulk concentration gradients, and, at very large voltages, transient space charge. The article concludes with an overview of more general situations involving surface conduction, multi-component electrolytes, and Faradaic processes.Comment: 10 figs, 26 pages (double-column), 141 reference

Fatty Acids of Erythrocyte Membranes and Blood Serum in Differential Diagnosis of Inflammatory Bowel Diseases

Aim: to study fatty acid levels in erythrocyte membranes (RBC) and blood serum (BS) in patients with inflammatory bowel diseases (IBDs) to develop differential diagnostic models including fatty acids as biomarkers to distinguish between nosological entities of IBDs (ulcerative colitis — UC, Crohn's disease — CD, unclassified colitis — UCC).Materials and methods. We examined 110 patients (mean age 37,7 ± 12,1 years) with IBDs and 53 healthy patients in control group (43,3 ± 11,7 years). The IBDs group included 50 patients with UC, 41 patients with CD, 19 patients with UCC. An exacerbation of the disease was revealed in 42 patients (84 %) with UC, 34 patients with CD (82.9 %) and 11 people with UCC (57.9 %). The study of fatty acids (FA) composition of RBC membranes and BS was carried out using GC/MS system based on three Agilent 7000B quadrupoles (USA).Results. The most significant for distinguishing active UC from CD exacerbation were serum levels of elaidin (p = 0.0006); docosatetraenoic (n-6) (p = 0.004); docodienic (n-6) (p = 0.009); omega-3/omega-6 ratio (p = 0.02); docosapentaenoic (n-3) (p = 0.03); the sum of eicosapentaenoic and docosahexaenoic (p = 0.03), as well as the content of RBC lauric FA (p = 0.04) (AUC — 0.89, sensitivity — 0.91, specificity — 0.89, diagnostic accuracy — 0.91). To distinguish active UC from the same of UCC, the following serum FA were found to be significant: alpha-linolenic; saturated (pentadecanoic, palmitic, stearic, arachidic); monounsaturated (palmitoleic, oleic); omega-6 (hexadecadienic, arachidonic) (p = 0.00000011—0.03300000) (AUC — 0.995, sensitivity — 0.98, specificity — 0.96, diagnostic accuracy — 0.97). The most significant in distinguishing patients with active CD from UCC exacerbation were levels of the following FA: alpha-linolenic; palmitoleic; oleic; the amount of saturated fatty acids (SFA); total unsaturated fatty acids (UFA); stearic; monounsaturated fatty acids (MUFA) amount; SFA/UFA; SFA/PUFA (polyunsaturated fatty acids); linoleic; total PUFA n6; lauric; arachidic acid (p = 0.0000000017–0.030000000) (AUC — 0.914, sensitivity — 0.90, specificity — 0.87, diagnostic accuracy — 0.91).Conclusion. The study of FA levels in groups with different nosological forms of IBDs using complex statistical analysis, including machine learning methods, made it possible to create diagnostic models that differentiate CD, UC and UCC in the acute stage with high accuracy. The proposed approach is promising for the purposes of differential diagnosis of nosological forms of IBDs

Observational Diagnostics of Gas Flows: Insights from Cosmological Simulations

Galactic accretion interacts in complex ways with gaseous halos, including galactic winds. As a result, observational diagnostics typically probe a range of intertwined physical phenomena. Because of this complexity, cosmological hydrodynamic simulations have played a key role in developing observational diagnostics of galactic accretion. In this chapter, we review the status of different observational diagnostics of circumgalactic gas flows, in both absorption (galaxy pair and down-the-barrel observations in neutral hydrogen and metals; kinematic and azimuthal angle diagnostics; the cosmological column density distribution; and metallicity) and emission (Lya; UV metal lines; and diffuse X-rays). We conclude that there is no simple and robust way to identify galactic accretion in individual measurements. Rather, progress in testing galactic accretion models is likely to come from systematic, statistical comparisons of simulation predictions with observations. We discuss specific areas where progress is likely to be particularly fruitful over the next few years.Comment: Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dave, to be published by Springer. Typos correcte

Natural Focality of Lyme Borreliosis, Granulocytic Anaplasmosis, and Monocytic Ehrlichiosis in Humans in the Republic of Tatarstan

Objective of the study is to investigate natural focality of Ixodidae tick borreliosis, granulocytic anaplasmosis, monocytic ehrli-chiosis in humans in the Republic of Tatarstan. Materials and methods. Utilized were the data from tick studies conducted between 2010–2015. Applying immune-enzymatic analysis, investigated were the blood sera from residents (donors) of Kazan and municipal districts of the Republic of Tatarstan for the presence of specific antibodies to borreliosis, ehrlichiosis, and anaplasmosis pathogens. Results and conclusions. For the first time ever, the data on spontaneous carriage of Ehrlichiosis pathogens in Ixodidae ticks have been obtained. The information received is an indicative of the active circulation of Borrelia, Ehrlichia and Anaplasma in the territory of the region and of necessity to expand the research on the “novel” for the Republic nosological forms of natural-focal infections

Gas Accretion and Star Formation Rates

Cosmological numerical simulations of galaxy evolution show that accretion of metal-poor gas from the cosmic web drives the star formation in galaxy disks. Unfortunately, the observational support for this theoretical prediction is still indirect, and modeling and analysis are required to identify hints as actual signs of star-formation feeding from metal-poor gas accretion. Thus, a meticulous interpretation of the observations is crucial, and this observational review begins with a simple theoretical description of the physical process and the key ingredients it involves, including the properties of the accreted gas and of the star-formation that it induces. A number of observations pointing out the connection between metal-poor gas accretion and star-formation are analyzed, specifically, the short gas consumption time-scale compared to the age of the stellar populations, the fundamental metallicity relationship, the relationship between disk morphology and gas metallicity, the existence of metallicity drops in starbursts of star-forming galaxies, the so-called G dwarf problem, the existence of a minimum metallicity for the star-forming gas in the local universe, the origin of the alpha-enhanced gas forming stars in the local universe, the metallicity of the quiescent BCDs, and the direct measurements of gas accretion onto galaxies. A final section discusses intrinsic difficulties to obtain direct observational evidence, and points out alternative observational pathways to further consolidate the current ideas.Comment: Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dav\'e, to be published by Springe

Применение рибосомального препарата рибомунила для коррекции иммунной системы у больных хроническим бронхитом

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Analysis of the epidemiological situation on the natural focal zooantroponozam Begional Infectious Pathology in the Republic of Tatarstan. Ixodes tick-borne Lyme disease. Ehrlichiosis and anaplasmosis. Hemorragic fever with renal syndrome (HFRS)

The study of long-term indicators of the level, structure and dynamics of the incidence of HFRS in the territory of the Republic of Tatarstan has shown that it has a wavy character with a tendency to increase and stabilize at a high level. Geographical spread of the infection is characterized by marked unevenness: the bulk of cases - 98% are landscape- geographical zones and Zakamye Predvolzhja. Analysis of the incidence of infection conditions showed that pockets of forest and dominated by household type, which accounted for 69% of morbidity. The continuing high incidence of HFRS in the Republic of Tatarstan for further study of the causes and conditions for the spread of infection to the development of a set of measures to prevent and reduce morbidity.Изучение многолетних показателей уровня, структуры и динамики заболеваемости ГЛПС на территории Республики Татарстан показал, что она имеет волнообразный характер с тенденцией к росту и стабилизации на высоком уровне. Территориальное распространение инфекции характеризуется выраженной неравномерностью: основная доля заболевших - 98% приходится на ландшафтно-географические зоны Закамья и Предволжья. Анализ заболеваемости по условиям заражения показал, что преобладают очаги лесного и бытового типа, на долю которых приходится 69% всей заболеваемости. Сохраняющийся высокий уровень заболеваемости ГЛПС в Республике Татарстан требует дальнейшего изучения причин и условий распространения инфекции для разработки комплекса мероприятий по предупреждению и снижению заболеваемости