H2S prevents the disruption of the blood-brain barrier in rats with prenatal hyperhomocysteinemia.

Elevation of the homocysteine concentration in the plasma called hyperhomocysteinemia (hHCY) during pregnancy causes a number of pre- and postnatal developmental disorders. The aim of our study was to analyze the effects of H2S donors -NaHS and N-acetylcysteine (NAC) on blood-brain barrier (BBB) permeability in rats with prenatal hHCY. In rats with mild hHCY BBB permeability assessed by Evans Blue extravasation in brain increased markedly throughout life. Administration of NaHS or NAC during pregnancy attenuated hHCY-associated damage and increased endogenous concentrations of sulfides in brain tissues. Acute application of dl-homocysteine thiolactone induced BBB leakage, which was prevented by the NMDA receptor antagonist MK-801 or H2S donors. Rats with hHCY demonstrated high levels of NO metabolite - nitrites and proinflammatory cytokines (IL-1ß, TNF-α, IL-6) in brain. Lactate dehydrogenase (LDH) activity in the serum was higher in rats with hHCY. Mitochondrial complex-I activity was lower in brain of hHCY rats. NaHS treatment during pregnancy restored levels of proinflammatory cytokines, nitrites and activity of the respiratory chain complex in brain as well as the LDH activity in serum. Our data suggest that H2S has neuroprotective effects against prenatal hHCY-associated BBB disturbance providing a potential strategy for the prevention of developmental impairments in newborns.

Interspecies Interaction of Bacteria Listeria monocytogenes, Yersinia pseudotuberculosis, and Marine Saprotrophs during Long-Term Culturing in Biofilms.

All bacterial strains studied retained the viability and ability to form both mono- and polycultural biofilms under conditions of long-term culturing in artificial seawater at 6°C and without addition of nutrients. Bacillus sp. and Pseudomonas japonica presumably stimulated the growth and reproduction of the pathogenic bacteria Listeria monocytogenes and Yersinia pseudotuberculosis. Preserved cell viability in a monoculture biofilm for a long period without adding a food source can indicate allolysis. At the same time, in a polycultural biofilm, the metabolites secreted by saprotrophic strains can stimulate the growth of L. monocytogenes and Y. pseudotuberculosis.

[Morphological aspects of diaphragm dysfunction in COVID-19-associated pneumonia]. / Morfologicheskie aspekty disfunktsii diafragmy pri COVID-19-assotsiirovannoi pnevmonii.

OBJECTIVE: To assess morphological changes in the diaphragm and phrenic nerve in patients who died from COVID-19. MATERIAL AND METHODS: In a case-control study, an analysis was made of autopsy material of the diaphragm and phrenic nerve of those who died from COVID-19 infection complicated by SARS-CoV-2-associated pneumonia, confirmed in vivo by the presence of SARS-CoV-2 RNA (Group 1, n=12), and those who died with a diagnosis of acute cerebrovascular accident of the ischemic type without parenchymal respiratory failure (Group 2, n=3). RESULTS: The main histopathological features in the diaphragm of the 1st group were the edema of the pericellular spaces of muscle fibers, edema of perivascular spaces, diapedese hemorrhages, plethora in arteriolas, in most veins and capillaries, red blood clots were revealed; in the diaphragmatic nerve - swelling of the perineral space, severe edema around the nerve fibers inside the nerve trunk. In the diaphragm of group 2, edema of pericellular spaces of muscle fibers and edema of perivascular spaces were less pronounced (p<0.001), hemorrhages were not determined; in the diaphragmatic nerve, moderate edema of the perineral space, mild swelling inside the nerve trunk around the nerve fibers was revealed (p<0.001). The glycogen content in the muscle cells of group 1 is significantly lower compared to group 2 (p<0.001). CONCLUSION: The study confirms the characteristic pathological picture of organ damage in COVID-19. However, the leading pathological mechanism of organ damage requires further investigation.

[Features of assessing the quality of medical care for patients with chronic heart failure of older age groups (review).]

The review presents a literature analysis on the quality of medical care in general and the criteria for their assessment. The main discussion is conducted in several areas: what indicators are currently available; which of them can be used in elderly and senile age groups; what indicators should be used in this category of patients. Based on the review, it should be concluded, that the existing quality indicators do not reflect the specifics of providing care to elderly and senile people with chronic heart failure. It is concluded, that many issues have not yet been resolved and further research is needed on this issue. In our opinion, the assessment of the quality of medical care for chronic heart failure, primarily in elderly and senile patients, should be carried out taking into account age characteristics and using additional quality indicators, which should be introduced in a separate paragraph in the profile order.

Finding of Molars of the Archaic Vole Lasiopodomys (Stenocranius) Gregaloides (Hinton, 1923) (Mammalia, Rodentia, Cricetidae) in the Late Pleistocene of the Southern Urals.

A total of 1250 lower first molars (m1) of voles (Arvicolini) were studied from Late Pleistocene deposits (the radiocarbon dates from rodent bones: 17 100 ± 50 IGANAMS-9117; 13 255 ± 60 IGANAMS-9116) of the Imanay Cave (southern Urals, 53°02' N, 56°26' E). Of these, 24 m1 of voles of the subgenus Stenocranius were found to have broadly connected triangles T4 and T5 (Pitymys-Rhombus) at the base of the anteroconid. This structure is characteristic of lower m1 of Lasiopodomys (Stenocranius) gregaloides (Hinton, 1923) from faunas of the second half of the Early Pleistocene and the first half of the Middle Pleistocene. Molars with such morphology have not been found so far in the Late Pleistocene and Holocene locations of Europe and the Urals.

[THE COMBINATION OF HIGH-FREQUENCY ELECTRICAL STIMULATION AND FIBRIN GLUE IN THE TREATMENT OF DECUBITAL ULCERS IN PATIENTS AFTER BRAIN DAMAGE: A PILOT STUDY].

Aim - to improve the results of treatment of decubital ulcers (DU) in combination therapy of high-frequency electrical stimulation (HFS) and fibrin glue (FG). The authors carried out a comparative analysis of the effectiveness of the combined method of treatment of decubital ulcers using high-frequency electrical stimulation (HFS) and fibrin glue (FG). All patients included in the pilot project, 22 people with a stage III pressure ulcer and who are in chronic critical condition after various brain damage. During the dressings, high-frequency stimulation was carried out with an EHVCh-250 "KiK Medimaster" electrosurgical apparatus, which generates alternating currents of the radio frequency (RF) range (0.3-3.0 MHz) for 28 days, and then (the main group), cryoprecipitate (fibrin glue) within 21 days. For comparison, the results obtained were compared with those in 25 people with DU treated according to the generally accepted method with the use of standard drugs (levomekol, levosin). HFS has a beneficial effect on all stages of a complicated wound process, promotes wound cleansing, activation of early granulation growth and marginal epithelialization. And the subsequent use of fibrin glue causes an even greater prevalence of proliferative processes over inflammatory processes in the tissues, which also contributes to a decrease in exudation, further growth of granulation tissue and an increase in epithelization processes. The use of this combination in the treatment of decubital ulcers can be used in complex conservative therapy in the treatment of pressure ulcers.

Stress load and neurodegeneration after gastrostomy tube placement in amyotrophic lateral sclerosis patients.

Dysphagia and progressive swallowing problems due to motoneuron death is one of amyotrophic lateral sclerosis (ALS) symptoms. Malnutrition and body weight loss result in immunological disturbances, fatigability and increase risk of secondary complications in ALS patients, percutaneous endoscopic gastrostomy tube (PEG) placement representing a well-recognized method for malnutrition correction and potentially increasing life expectancy. However, despite nutritional correction, occasional rapid neurological deterioration may develop after PEG placement. We have hypothesized that this decline can be a result of exteroceptive stress during PEG placement and promote neurodegeneration in ALS patients. Intravenous sedation may decrease stress during invasive procedures and it is safe during PEG placement in ALS patients. The aim of the study was comparing different PEG placement protocols of anesthesia (local anesthesia or local anesthesia plus intravenous sedation) in ALS from perspectives of stress load and neurological deterioration profile. During 1.5 years 94 ALS patients were admitted; gastrostomy was performed in 79 patients. After screening according to inclusion and exclusion criteria, 30 patients were included in the prospective consecutive study. All patients were divided in two groups, with local anesthesia and with combination of local anesthesia and intravenous sedation. Routine biochemical indices, neurodegeneration and stress markers were measured. The age of ALS patients was 61 ± 10 years; 20 patients were included at stage 4A and 10 at stage 4B (King's College staging). PEG was placed at average14 months after the diagnosis and 2.2 years after first symptoms. Mean ALS Functional Rating Scale-Revised was 27.8, mean forced vital capacity of lung 46.3% (19-91%). After one year of observation only 8 patients survived. Mean life duration after PEG was 5 months (5 days-20 months). Comparison of two PEG placement protocols did not reveal differences in survival time, stress load and inflammation level. Higher saliva cortisol levels, serum cortisol, glucose, C-reactive protein and interleukin-6 were detected after PEG placement, confirming considerable stress response. PEG is a stressful factor for ALS patients, PEG placement representing a natural model of exteroceptive stress. Stress response was detected as increased cortisol, C-reactive protein, interleukin-6, and glucose levels. Intravenous sedation did not increase the risk of PEG placement procedure, however, sedation protocol did not affect stress load.

Modeling of Interspecific Interaction of Yersinia pseudotuberculosis and Listeria monocytogenes in a Mixed-Species Biofilms with Microorganisms Isolated from Coastal Waters of the Sea of Japan.

We studied the possibility of formation of mixed-species biofilms by Yersinia pseudotuberculosis and Listeria monocytogenes with marine saprotrophic bacteria Flavobacterium sp. and Micrococcus luteus isolated from the coastal waters of the Sea of Japan in summer. Model experiments showed that Flavobacterium sp. and Micrococcus luteus can form both single- and mixed-species biofilms with the specified pathogenic bacteria thus stimulating their growth. This can contribute to the preservation of the pathogens in the marine environment.

Heart failure with preserved left ventricular ejection fraction in patients with obstructive sleep apnea syndrome: prognostic value of biomarkers.

Aim      To study the role of soluble ST2 (sST2), N-terminal pro-brain natriuretic peptide (NT-proBNP), and С-reactive protein (CRP) in patients with chronic heart failure and preserved left ventricular ejection fraction (CHF with pLVEF) and syndrome of obstructive sleep apnea (SOSA) in stratification of the risk for development of cardiovascular complications (CVC) during one month of a prospective observation.Material and methods  The study included 71 men with SOSA with an apnea/hypopnea index (AHI) >15 per hour, abdominal obesity, and arterial hypertension. Polysomnographic study and echocardiography according to a standard protocol with additional evaluation of left ventricular myocardial fractional changes and work index were performed for all patients at baseline and after 12 months of observation. Serum concentrations of sST2 , NT-proBNP, and CRP were measured at baseline by enzyme-linked immunoassay (ELISA).Results The ROC analysis showed that the cutoff point characterizing the development of CVC were sST2 concentrations ≥29.67 ng/l (area under the curve, AUC, 0.773, sensitivity 65.71 %, specificity 86.11 %; p<0.0001) while concentrations of NT-proBNP (AUC 0.619; p=0.081) and CRP (AUC 0.511; р=0.869) were not prognostic markers for the risk of CVC. According to data of the ROC analysis, all patients were divided into 2 groups based on the sST2 cutoff point: group 1 included 29 patients with ST2 ≥29.67 ng/l and group 2 included 42 patients with ST2 <29.67 ng/l. The Kaplan-Meyer analysis showed that the incidence of CVC was higher in group 1 than in group 2 (79.3 and 28.6 %, respectively, p<0.001). The regression analysis showed that adding values of AHI and left ventricular myocardial mass index (LVMMI) to sST2 in the model increased the analysis predictive significance.Conclusion      Measuring sST2 concentration may be used as a noninvasive marker for assessment of the risk of CVC development in patients with CHF with pLVEF and SOSA within 12 months of observation. Adding AHI and LVMMI values to the model increases the predictive significance of the analysis.

[Analysis of healthcare for patients with cardiovascular diseases in Russian Federation in comparison with the practice of Europe and USA].

The medical community, researchers and healthcare organizers are constantly challenged by comparing key indexes reflecting the effectiveness of cardiovascular care, primarily for the dynamic assessment and implementation of the world's best practices to reduce cardiovascular mortality. The analysis of health care for patients with cardiovascular diseases (CVD) is a complex, multicomponent process, the structure and key tools of which differ from country to country. Using different data sources, methodological and analytical approaches creates certain limitations and barriers to the assessment. In order to update the ideas about the modern coordinate system and tools for assessing cardiovascular care, the authors presented practices for analyzing major indexes in Russia, European countries, and the United States. The review presents sources of statistical data, principles for assessing risk factors, cardiovascular morbidity and mortality, and specific features of monitoring the availability and quality of cardiovascular care.

[Long-term postoperative outcomes in patients with drug-resistant epilepsy]. / Otdalennye rezul'taty khirurgicheskogo lecheniya patsientov s farmakorezistentnymi formami epilepsii.

Epilepsy surgery is effective in 30-82% of patients with drug-resistant epilepsy. However, risk factors of unfavorable outcomes after epilepsy surgery require further study. OBJECTIVE: To evaluate risk factors of favorable and unfavorable long-term postoperative outcomes in patients with drug-resistant epilepsy. MATERIAL AND METHODS: Postoperative outcomes in a large cohort of patients with epilepsy are reported for the first time in the Russian Federation. There were 271 patients with drug-resistant scheduled for surgery. Preoperative examination and surgical treatment were carried out between January 1, 2014 and December 12, 2019 at the Evdokimov Moscow State University of Medicine and Dentistry and Sklifosovsky Research Institute for Emergency Care. We used Engel grading system to assess postoperative outcomes after 12, 24, 48 and 60 months. We distinguished favorable (Engel I-II) and unfavorable (Engel III-IV) outcomes and analyzed the factors influencing postoperative results in these patients. RESULTS: There were 319 surgical procedures in 271 patients (217 primary resections, implantation of vagus nerve stimulator in 31 patients, 9 redo resections and 8 radiosurgical procedures). Focal cortical dysplasia (FCD) was found in 162 (60%) patients, «dual pathology¼ - in 118 (44%) cases. In 12 months after surgery, favorable outcomes (Engel l-II) were observed in 69% of patients (n=148), after 24 months - in 71% (n=127) of patients. Postoperative complications occurred in 6 (1.9%) patients. There was no mortality. The earlier onset of epilepsy (p=0.01), multifocal (p=0.002) and bilateral lesions (p=0.0038) were the most significant risk factors of unfavorable postoperative outcomes. CONCLUSION: Surgical resection is effective approach for drug-resistant epilepsy.

[Possibilities for predicting of cardiac arrhythmias and conductivity disorders in former athletes.]

In order to analyze the relationship between the athletic qualification and syndrome of cardiac rhythm and conductivity disturbances in former athletes, a retrospective analysis of medical records of 39 male former athletes with cardiovascular complaints (mean age 61,6±11,3 years, mean duration of career in sports 23,9±17,3 years, mean duration of post-athletic period 20,1±9,9 years) was carried out. The patients were screened for cardiac arrhythmias and underwent echocardiography. The overall prevalence of sustained paroxysms of atrial fibrillation was 42%, increasing with the athletic qualification. Ryan grade 4b-5 premature ventricular contractions were found in 14% of patients. 3 parameters were found to be the independent predictors of arrhythmias in former athletes, i. e. athletic qualification, multifocal atherosclerosis (as an anti-risk factor), and age. The coefficient of determinance for the created prognostic model reached 43%. Further prospective studies are needed to validate an algorithm.

[Results of analysis of the prescriptions for elderly patients in ambulatory practice.]

A randomized retrospective analysis of medical records of patients aged 65 years and older receiving ambulatory medical care was carried out in order to assess drug prescriptions for the detection of polypharmacy and potentially dangerous and significant drug interactions. The average number of visits per patient over 65 is 11,2±8,4. Comorbidity was detected in 89,4% of patients. Polypharmacy was detected in 76,6% of patients. In 1/3 of cases, patients were prescribed not recommended drugs (Beers criteria 2015). Authors found 364 interactions of various hazard categories. The obtained data shows that it is mandatory to implement various systems of prescription audit for the timely detection of potentially hazardous and incompatible drugs, as well as to correct prescriptions and improve efficacy and safety of drug use in patients older than 65 years.

[Factors limiting nutritional support for patients in chronic critical illness].

Patients in chronic critical illness after brain injury may experience various conditions that limit nutritional support. The aim of this work is to analyze the factors limiting or hindering the provision of nutritional support (in particular, enteral clinical nutrition) in patients in chronic critical illness after brain damage. Material and methods. This study is a prospective observational cohort study. In the course of the study, 47 patients (27 men and 20 women, mean age 52±18.4 years) in a chronic critical illness who were undergoing rehabilitation after brain damage and who had certain limitations in the provision of nutritional support were evaluated. The duration of the patients' stay in the intensive care unit was from 21 to 30 days. During hospitalization, adverse events and conditions were recorded in these patients, limiting the conduct of enteral clinical nutrition. Results. Among the undesirable phenomena and conditions limiting enteral nutrition, diarrheal syndrome most often developed - in 41.7% of patients (associated with the use of antibiotics in 25.0% of the examined). The second group in terms of frequency - the development of surgical pathology (of various etiology) - in 31.7% of patients, which attracted special attention, taking into account the neurological and/or neurosurgical nature of the underlying disease. At the same time, the appearance of a high residual volume of the stomach against the background of an increase in hydrocephalus developed only in 5.0% of cases. More attention should be paid to patients who are in the most severe physical condition, since they have a high probability of the occurrence of several factors at once that limit the use of clinical nutrition - this category of the studied sample included 19.1% of patients. Conclusion. Strict adherence to the technology of enteral nutrition can increase the efficiency of enteral nutrition in patients in chronic critical condition.

[LOW-ENERGY LASER TECHNOLOGY IN THE COMPLEX TREATMENT OF PRESSURE SORES IN PATIENTS WITH SEVERE BRAIN DAMAGE].

Aim - to improve the results of treatment of pressure sores using low-energy laser technology. The authors performed a comparative analysis of the effectiveness of the use of low-energy laser irradiation in the complex treatment of pressure ulcers of 2-3 degrees in 35 patients with severe brain damage for the period from 2017-2019. The contact laser was used with the following parameters: wave length - 904 nm, frequency - 5000 Hz, irradiation mode - pulsed, power - 13.5mWt/cm2, exposure - on average 2 minutes per zone. The results were compared with those in 41 people treated according to the traditional methodology. The demographic criteria, localization and length of the process did not have significant intergroup differences. The use of low-energy laser technology in combination with other conservative methods made it possible to accelerate the healing of pressure sores by 1.3-1.4 times, and to reduce the degree of microbial contamination of the focus in earlier periods (p<0.05). At the same time, both the duration of the inpatient rehabilitation phase and the overall treatment costs are reduced. An integrated approach using low-energy laser technology as an additional physical factor can significantly improve the results of the treatment of pressure sores in people with severe brain damage.

Establishing a hepatitis C continuum of care among HIV/hepatitis C virus-coinfected individuals in EuroSIDA.

OBJECTIVES: The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)-coinfected individuals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct-acting antiviral (DAA) therapy. METHODS: Stages included in the continuum were as follows: anti-HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow-up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow-up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24 weeks after stopping treatment. RESULTS: Numbers and percentages for the stages of the HCV continuum of care were as follows: anti-HCV positive (n = 5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n = 3876), initiated HCV treatment (1693 of 3876; 43.7%), completed HCV treatment (1598 of 3876; 41.2%), follow-up HCV RNA test to allow SVR assessment (1195 of 3876; 30.8%), and cure (629 of 3876; 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P < 0.0001). CONCLUSIONS: In the proposed HCV continuum of care for HIV/HCV-coinfected individuals, we found major gaps at all stages, with almost 20% of anti-HCV-positive individuals having no documented HCV RNA test and a low proportion achieving SVR, in the pre-DAA era.

The Missing Link: How Exosomes and miRNAs can Help in Bridging Psychiatry and Molecular Biology in the Context of Depression, Bipolar Disorder and Schizophrenia.

MicroRNAs (miRNAs) only recently have been recognized as promising molecules for both fundamental and clinical neuroscience. We provide a literature review of miRNA biomarker studies in three most prominent psychiatric disorders (depression, bipolar disorder and schizophrenia) with the particular focus on depression due to its social and healthcare importance. Our search resulted in 191 unique miRNAs across 35 human studies measuring miRNA levels in blood, serum or plasma. 30 miRNAs replicated in more than one study. Most miRNAs targeted neuroplasticity and neurodevelopment pathways. Various limitations do not allow us to make firm conclusions on clinical potential of studied miRNAs. Based on our results we discuss the rationale for future research investigations of exosomal mechanisms to overcome methodological caveats both in studying etiology and pathogenesis, and providing an objective back-up for clinical decisions.

Neuronal damage and neuroinflammation markers in patients with autoimmune encephalitis and multiple sclerosis.

Inflammatory diseases of the central nervous system (CNS) are a diagnostic challenge to clinicians. Autoimmune encephalitis (AE) is an important diagnostic consideration in patients with CNS inflammatory disorders; despite of a wide range of neuropsychiatric symptoms it should be diagnosed as soon as possible and the patient transferred to the neurologist. We studied a group of AE patients (n = 24) as compared to multiple sclerosis (MS, n = 61) and control (n = 19) groups. Detailed clinical pictures of patients are presented. We focused on relevant cerebrospinal fluid (CSF) tests like protein levels, cytosis and oligoclonal bands, neuroinflammation indices (interleukin-6, soluble receptor of IL-6, neopterin, anti-ribosomal proteins antibodies) and markers of neurodegeneration (phosphorylated neurofilament heavy chain, pNfh). Elevated neopterin level was found in AE group as compared to the MS and control groups, while protein and pNfh were increased in both AE and MS groups. In the MS group, the cytosis and soluble receptor of IL-6 were higher as compared to the control group. Anti-ribosomal proteins antibodies were increased in a single patient with AE. High levels of protein were predictive of mortality in AE patients, while IL-6 and pNfh were elevated in severe AE patients. AE patients with paraneoplastic etiology demonstrated oligoclonal bands positivity. Taken together, our results suggest the neopterin as an additional marker of autoimmune brain inflammation. Though higher levels of protein, IL-6 and pNfh were found in patients with severe disease progression and death, prognostic values of these markers should be validated in larger cohorts of patients.

[Plasma D-dimer volume as a subclinical marker of thrombotic risk in elderly patients with atrial fibrillation.]

Aged patients with atrial fibrillation (AF) are at high risk of both thromboembolic and haemorrhagic complications of disease and of its treatment. A study was provided to assess the role of D-dimer plasma level as a marker of thrombosis in aged patients with AF having no clinical signs of active thrombosis depending on used treatment strategy and quantitative thrombotic and haemorrhagic risk of AF. The results show that D-dimer plasma levels correlate with scores of thromboembolic and haemorrhagic risks in group on antiplatelet agents but not anticoagulants, with the difference in D-dimer level driven by subgroup on CHA2DS2-VASc score ≥5. High D-dimer level was associated with in-hospital mortality and rhythm of AF at the moment of blood sample collection. Therefore, an accuracy of risk prognosis of fatal complications of AF for elderly patients may be increased by using the laboratory markers of thrombus formation such as D-dimer and by using the obtained results to guide an antithrombotic therapy.

Interaction of Salmonella enteritidis and Salmonella typhimurium in Microbial Association Formed by Them in In Vitro Experiment.

We studied the interaction of Salmonella enteritidis and Salmonella typhimurium in the microbial association formed by these microorganisms in vitro. It was found that S. typhimurium in microbial association in LB-broth inhibited reproduction of S. enteritidis, which attested to its higher competitiveness. The concentration of S. typhimurium in the medium in 6 h reached 92-93% of the total number of bacteria. Parallel growth of the populations of S. enteritidis and S. typhimurium was observed only during the first hour, but later, S. typhimurium always exceeded S. enteritidis by the growth dynamics. The competitive advantage of S. typhimurium was observed both in the absence and presence of 60-MDa virulence plasmid.