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At an international online expert meeting held on September 16, 2021, the results of the empagliflozin research program EMPA-REG Outcome, EMPEROR-Reduced and EMPEROR-Preserved were reviewed. We analyzed cardiovascular and renal outcomes during the treatment with empagliflozin in patients with chronic heart failure, regardless of the presence of type 2 diabetes mellitus. The positive results of the EMPEROR-Preserved study are updated and their significance for clinical practice is discussed. Several proposals have been adopted that will accelerate the introduction of empagliflozin therapy into practice in patients with heart failure and overcome clinical inertia.

Brief intensive behavioral interventions which promise a one session miracle cure from drug or alcohol dependence are very common in the Russian addiction psychiatry, particularly in its commercial domain. Unlike traditional shamanism these behavioral interventions are presented to the patients as the most recent advances in the main stream addiction medicine and therefore they can be called "scientifically decorated shamanism". The paper includes classification of these methods, reasons for this phenomenon to be so common in the Russian addiction psychiatry (narcology), and also possible approaches to the modernization of the Russian narcology system with evidence based approach to research and clinical practice to be the major one.

Background: Melatonin is known to modulate circadian and seasonal rhythms in metabolism, reproduction, and behavior. However, the effect of exogenous melatonin supplementation on the functioning of the thyroid and adrenal glands in species without a clear seasonality in reproduction is still unclear., Aim: Using a meta-analysis of publications, to investigate the effect of melatonin monotherapy on the concentrations of pituitary thyroid-stimulating hormone, thyroid hormones (TG), pituitary adrenocorticotropic hormone and corticosterone (CS) in rats kept under standard laboratory conditions., Materials and Methods: In our work, using the Review Manager 5.3 program, we conducted a meta-analysis of publications examining the effect of melatonin monotherapy on the functioning of the thyroid gland (22 papers) and adrenal glands (20 papers) in rats kept under standard conditions., Results: According to the results of our meta-analysis, the effects of melatonin on the levels of TG and CS depend on the dose and duration of therapy. A decrease in TG and CS was associated with therapy lasting no more than 4-5 weeks and with high doses of melatonin. An increase in CS and a trend toward increased TG levels were observed with longer therapy. However, a few studies have observed a decrease in TG with very long-term melatonin therapy (≥32 weeks). Among all TGs, total thyroxine (T4) showed maximum sensitivity to exogenous melatonin, which indicates the influence of melatonin on the secretory function of the thyroid gland. In addition, melatonin increased the relative weight of the adrenal glands. There was no convincing evidence that the effects of melatonin were influenced by the route and timing of administration, or the timing of blood sampling., Conclusion: As a result, exogenous melatonin can modulate TG and CS levels, even in species without a clear seasonality in reproductive function.

Despite the presence of various signs of cardiac amyloidosis ("red flags"), the introduction into routine practice of new non-invasive diagnostic methods (Speckle Tracking technology using echocardiography, myocardial scintigraphy with technetium pyrophosphate, genetic testing, screening for free light chains of immunoglobulins to exclude AL-amyloidosis), which have high specificity and sensitivity, transthyretinic (ATTR) cardiomyopathy is still a difficult to diagnose disease, especially in the early stages when treatment is most effective. The article presents a clinical case of ATTR-amyloidosis with predominant heart damage, manifested by severe diastolic heart failure resistant to treatment. The timing, from the moment of the first episode of decompensation of heart failure to death, is 4 months, which confirms the rapid progression of severe biventricular dysfunction of the heart. Despite the presence of cardiac and extracardial "red flags" of ATTR-amyloidosis in the patient, the diagnosis was established at autopsy. The paper analyzes possible errors of early diagnosis at the outpatient and inpatient stages of patient management.

Patients with rheumatic diseases infected with hepatitis B virus (HBV) are difficult to manage not only due to the presence of risk factors for the development and rapid progression of liver cirrhosis, but also due to the likelihood of reactivation of this infection. Despite the successes achieved in the fight against HBV, the virus cannot be completely defeated due to the presence of hidden forms of the disease, escaping the field of vision of a rheumatologist and an infectionist. Based on the results of the analysis of current publications, the paper presents the rationale for a complete immunological screening of patients with rheumatic diseases when prescribing antirheumatic therapy. The issues of the role of COVID-19 in the exacerbation of chronic viral hepatitis B, antiviral prevention and monitoring are discussed, the classification of antirheumatic drugs according to the risk of HBV reactivation is presented.

The main treatment option of prolactin-secreting pituitary adenomas is dopamine agonist therapy, which demonstrates prolactin level normalizing and reducing the size of an adenoma in the majority of cases. However, significant amount of patients - about 20% - poorly responds even to high doses of dopamine agonists that is explained by the resistance to therapy. The occurrence of pharmacodynamic characteristics is one of the causes responsible for the development of resistance to typical therapy. Clinical manifestations of persistent hyperprolactinemia are due to following pathological factors: hormonal hypersecretion and the mass-effect of pituitary adenoma. Prevention of irreversible changes is possible only with timely detection of resistance and determination of the optimal personalized treatment algorithm.We report a clinical case of dopamine-agonist resistant microprolactinoma. Patient's health stabilisation, normal level of prolactin and reduction in size of adenoma were achieved due to administration of combined treatment with tamoxifen and dopamine agonists. Hyperprolactinaemia occurring because of prolactin-secreting pituitary adenoma and associated adverse effects are significant problem, decreasing quality of life and demographics in general. This underlines the importance of figuring out causes and identifying predictors of the therapy resistance.The results of the study, illustrated by a clinical example, are presented in the present paper.

This study is aimed at investigating epileptic seizures, one of the consequences of traumatic brain injury (TBI). Immediate and early post-traumatic seizures, as well as late post-traumatic epileptic seizures or post-traumatic epilepsy, can have different pathogenetic bases. The following key risk factors associated with post-traumatic epilepsy are known: duration of unconsciousness, gunshot wounds, intracranial hemorrhage, diffuse axonal injury, prolonged (more than 3 days) post-traumatic amnesia, acute subdural hematoma with surgical evacuation, immediate and early post-traumatic epileptic seizures, fracture of the skull bones. The role of genetic factors in post-traumatic seizures is poorly understood due to the complexity and multiple causal mechanisms. This paper addresses the role of genetic factors in the occurrence and severity of epileptic events in patients with TBI. In particular, we investigated the role of the Cys112Arg single nucleotide polymorphism of the apolipoprotein E gene. Apolipoprotein E is known for its role in the transport and metabolism of lipids and, therefore, the development of cardiovascular diseases; it is also associated with Alzheimer's disease and has recently been studied in the context of association with epilepsy. The study shows an association between this polymorphism and the risk of immediate and early epileptic seizures in patients with severe TBI.

Radiation therapy is one of the main treatment option for prostate cancer used either independently or as a component of combined and complex treatment of the disease. Modern achievements make it possible to deliver doses of radiation that match the exact dimensions of the tumor for greater efficacy, with minimal exposure of the surrounding tissues, however, does not eliminate them. In most patients, clinical manifestations of chronic radiation proctitis occur during the first 2 years after radiation therapy. The article summarizes the current knowledge about pathophysiology, clinical manifestations, diagnostics and treatment options for this condition. In this paper, we present a case of complicated of chronic radiation proctitis.

Glucagon-like peptide-1 receptor agonists (arGLP1) are an effective treatment for patients with type 2 diabetes mellitus (T2DM), mainly due to increasing insulin secretion and suppressing glucagon release by stimulating the respective receptors. Taking into account their positive effect on major cardiovascular events, drugs in this group with proven cardioprotective effects are recommended for patients with T2DM and clinical cardiovascular diseases or multiple cardiovascular risk factors. In this paper, we present an overview of current clinical studies on the clinical efficacy and safety of arGLP1 and discuss current prospects for arGLP1 as a therapy for patients with T2DM.

Leonid Vasilyevich Sobolev is an outstanding pathologist, whose name definitely should occupy an honorable place in the galaxy of great scientists of Russia. However, his name was undeservedly forgotten, and the role of his work was underestimated. This Russian scientist made the most important discovery: he proved in an experiment that it is the islets of Langerhans in the pancreas that secrete a humoral regulator, "factor X", the deficiency of which leads to diabetes mellitus. This mysterious islet factor will be isolated from the pancreas of dogs in 1921 by the future Nobel laureate Frederick G. Banting and will become part of the medicine as insulin. However, there is every reason to believe that the discovery of F. G. Banting, who repeated a series of experiments by Leonid Vasilyevich Sobolev, is, in fact, secondary, which is the research subject in this paper.

The progressive improvement of the classification using modern analytical methods is an essential tool for the development of precise and personalized approaches to the treatment of pituitary adenomas. In recent years, endocrinologists have witnessed evolutionary changes that have occurred in the histopathological identification of pituitary neoplasms, revealing new possibilities for studying tumorigenesis and predicting biological behavior.The paper considers the historical aspects of the gradual improvement of the classification of pituitary adenomas, as well as the new international 2022 WHO classification, according to which pituitary adenomas are included in the list of neuroendocrine tumors (PitNETs) to reflect the biological aggressiveness of some non-metastatic pituitary adenomas. The characteristics of pituitary adenoma are presented, as well as a list of histological subtypes of aggressive neuroendocrine tumors of the pituitary gland, marked by the main potentials for invasive growth, an increased risk of recurrence and a negative clinical prognosis.The expediency of changing the definition of «pituitary adenoma» to «neuroendocrine tumor» is discussed. It is emphasized that the introduction of a unified clinical, laboratory and morphological protocol into national clinical practice will help provide comparable comparative studies on the prognosis of the disease and the effectiveness of secondary therapy and also contribute to adequate management of potentially aggressive PitNETs.

Background:  Primary hyperparathyroidism (PHPT) is an endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH) with upper-normal or elevated blood calcium levels due to primary thyroid gland pathology. PHPT is a rare pathology in children, with a prevalence of 2-5:100,000 children according to the literature. Due to the non-specificity of clinical manifestations at onset (nausea, vomiting, abdominal pain, emotional lability), the disease may remain undiagnosed for a long time., Aim:  To study the features of the course and molecular genetic basis of primary hyperparathyroidism in children., Materials and Methods:  Retrospective observational study of 49 patients diagnosed with primary hyperparathyroidism. All patients underwent a comprehensive laboratory-instrumental and molecular genetic study at the Institute of Pediatric Endocrinology, Endocrinology Research Center of Russia in the period 2014-2022., Results:  The first clinical symptoms of PHPT were noted at the age of 13.8 years [10.6; 1 5.2], among which fatigue, headaches, dyspepsia, lower limb pain, and fractures were the most common. The age of diagnosis was 15.81 years [13.1; 16.8], all children were found to have high levels of PTH, total and ionized calcium, with hypophosphatemia in 93.9% of patients (n=46) and hypercalciuria in 43% (n=21). Five out of 49 patients (10.2%) were found to have ectopy of the thyroid: 3 showed an intrathyroidal location, 2 in the mediastinal region. Molecular genetic study revealed mutations in 32.7% of patients (n=16, CI (21; 47)), mutations in MEN1 being the most frequent (n=11). Pathogenic variants in CDC73 were detected in 3 patients, RET - in 2. Among the operated 39 patients, adenoma of the thyroid was detected in 84.6% of cases (n=33), hyperplasia in 7.7% (n=3), atypical adenoma in 5.1% (n=2), carcinoma in 5.1% of cases (n=2)., Conclusion:  The paper presents the peculiarities of the course and the results of molecular genetic study of pediatric PHPT. This sample is the largest among those published in the Russian Federation.

Breast cancer (BC) is a serious disease and is considered an important health problem worldwide. The prevalence of the disease in women according to Rosstat was 64,951 cases in the Russian Federation in 2020 (21.7% among all types of cancer).  Hormone-dependent estrogen receptor-positive (HR+), human epidermal growth factor receptor type 2 negative (HER2-) metastatic breast cancer (mBC) accounts for 70% of all cases.  About 40% of patients with ER+/HER2- mBC have mutations in the PIK3CA gene, leading to hyperactivation of the alpha isoform (p110α) of phosphatidylinositol 3-kinase (PI3K). Hormonal therapy with or without cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor is considered the standard treatment for patients with ER+/HER2- mBC. However, acquired resistance to this therapy remains a problem. Innovative methods for the treatment of breast cancer are the use of targeted therapeutic agents aimed at direct inhibition of the PI3K pathway in combination with hormone therapy. Alpelisib is a PI3Kα-specific inhibitor. Hyperglycemia is the most common side effect of alpelisib treatment. Currently, there is a consensus on the prevention and correction of hyperglycemia in patients receiving therapy with alpelisib, which recommends that before starting therapy, in  order to diagnose carbohydrate metabolism disorders and assess the risk of developing hyperglycemia, determine in all patients: the level of glycated hemoglobin (HbA1c), glucose fasting plasma (FPG), body mass index (BMI). And also to evaluate such risk factors as the presence of a family history of type 2 diabetes mellitus (DM 2), the presence of gestational diabetes in the patient's history, or the fact of the birth of children weighing more than 4 kilograms.Recently, new combinations of drugs have been actively used to treat disorders of carbohydrate metabolism, such as pioglitazone + metformin. This paper discusses the mechanism of action of PI3K inhibitors, new therapeutic combinations and their undesirable effects, and presents therapeutic experience.

Congenital nephrogenic diabetes insipidus (CNDI, arginine vasopressin resistance) is a rare inherited disorder characterized by insensitivity of the kidney to the antidiuretic effect of vasopressin. NDI is clinically characterized by polyuria with hyposthenuria and nocturia and polydipsia. In the majority of cases, about 90%, nephrogenic diabetes insipidus is an X-linked recessive disorder caused by mutations in the AVP V2 receptor gene (AVPR2). In the remaining cases, about 10%, the disease is autosomal recessive or dominant and, for these patients, mutations in the aquaporin 2 gene (AQP2) have been reported. To date, the nucleotide variants registered in AQP2 were sporadic, there is no data on the presence of «frequent» mutations and the prevalence of the disease both among the global population and among individual ethnic groups. In this paper, we describe 12 cases of arginine vasopressin resistance caused by a new homozygous mutation p.R113C in AQP2 presented among the indigenous population of the Republic of Buryatia.

The article describes the historical milestones in the study of Crohn's disease from the time of its original description in the 17th century, the revolution in the medical community after the landmark paper in 1932, to the present day. The history of Crohn's disease testifies to the discoveries of the past years, which open up to us the advantages of a scientific approach to the diagnosis and treatment of this disease.

Disease modifying therapy for adult patients with SMA still raises certain questions regarding its effectiveness, given the long-term chronic process with often significant neurological deficits at the time of initiation of therapy. This paper presents three clinical cases of adult sitter patients with SMA type 2, who began risdiplam therapy 16.5-41 years after the disease onset. All patients have been receiving therapy since 2020, at the time of observation for 2.5-3 years. All patients showed subjective and objective (using specialized scales) improvement during long-term therapy with risdiplam. In addition to an increase in muscle strength, mainly in the proximal and distal parts of the arms, several non-motor effects were also noted (including improved swallowing and breathing), which cannot be recorded using scales. No adverse events were recorded during therapy.

Acute pain syndromes caused by discogenic lumbosacral radiculopathy and lumboischialgia are not uncommon in clinical practice and characterized by a high risk of becoming chronic. The pathogenetic aspects, features of the clinical picture, existing approaches to conservative treatment of these conditions are analyzed in this paper. Data on the efficacy and safety of a fixed combination of diclofenac and orphenadrine (Neodolpasse) use in the treatment of vertebrogenic pain syndromes based on the NEODOLEX study results are presented, and the authors' own clinical observations are given. Possible reasons for the high efficacy of Neodolpasse in patients with discogenic radiculopathies and nonspecific back and neck pain are discussed.

Aim: To systematize data on the prevalence of the combination of functional dyspepsia (FD) and irritable bowel syndrome (IBS) using the Rome IIIIV Criteria., Materials and Methods: A search in electronic databases MEDLINE/PubMed, EMBASE, and Cochrane was conducted. The depth of search was 17 years (from January 2006 to May 2022). Original publications from peer-reviewed periodicals that applied the Rome IIIIV Criteria for diagnosis of FD and IBS in an adult patient population with detailed descriptive statistics to allow the resulting data to be included in the meta-analysis were selected for final analysis., Results: The final analysis included 38 studies involving 17,993 patients with FD and 15,883 patients with IBS. In the overall pool of studies using the Rome IIIIV Criteria, the pooled prevalence of FD in patients with IBS was 34.625% (95% confidence interval [CI] 28.15941.390), and the pooled prevalence of IBS in patients with FD was 37.549% (95% [CI] 31.51143.787). A random-effects model was used in the analyses since significant heterogeneity between results was found (p0.0001; I298%). Using the Rome III Criteria, the pooled prevalence of FD in patients with IBS was 31.993% (95% CI 26.13538.150; I2=98.17%), while the prevalence of IBS in patients with FD was 34.694% (95% [CI] 29.31940.273; I2=97,89%). An analysis of papers using the Rome IV Criteria demonstrated that the pooled prevalence of FD in patients with IBS was 42.614% (95% CI 18.58868.675; I2=98.97%), and the prevalence of IBS in patients with FD was 50.444% (95% CI 37.95662.904; I2=94,39%)., Conclusion: This meta-analysis demonstrated that the prevalence of the combination of FD and IBS identified using the Rome IIIIV Criteria is high and is reported in approximately 1 in 3 patients with the functional gastrointestinal disorders concerned. The prevalence of a combination of FD and IBS identified using the Rome IV Criteria is at least 10% higher than that using the Rome III Criteria.

Presents data on the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH), which serve as a rationale for approaches to the choice of treatment. CTEPH usually begins with persistent obstruction of the large and/or medium pulmonary arteries by organized thrombi. Impaired lysis of thrombi may be associated with abnormal fibrinolysis, hematological or autoimmune diseases. The molecular processes underlying the lesions of small vessels are not fully understand. The degree of small-vessel disease has a significant impact on the severity of CTEPH and postoperative outcomes. The CTEPH treatment has evolved with the development of three directions pulmonary endarterectomy, balloon angioplasty of pulmonary arteries and the use of specific therapy used for pulmonary arterial hypertension. The paper demonstrates the possibilities of a multimodal approach in the treatment of this category of patients.

The paper reveals the 5 cases date about blastic plasmacytoid dendritic cell neoplasm. The presented information demonstrates morphological, immunohistochemical data and clinical manifestations.

Kabuki syndrome is a rare hereditary disease characterized by distinctive facial features, skeletal abnormalities, mental retardation, developmental delay, and anomalies in multiple organ systems development.Congenital hyperinsulinism is a rare manifestation of his Kabuki syndrome. However, early diagnosis is crucial to prevent neurological complications of hypoglycemia.There are 2 types of Kabuki Syndrome depending on severity of symptoms. Kabuki syndrome Type 1 is associated with heterozygous mutations in gene KMT2D. Kabuki syndrome Type 2 is inherited in an X-linked manner. It's associated with heterozygous mutations in gene KDM6A and characterized by more severe course of the disease.This paper presents 2 cases of children with congenital hyperinsulinism as the feature of Kabuki syndrome Type 1 and Type 2.

Treatment of patients with long-term persistent symptoms after COVID-19 is an urgent problem for clinicians around the world. One of the most significant manifestations of post-COVID-19 syndrome is organizing pneumonia that is usually treat with corticosteroids. The paper presents a clinical case of typical course of post-COVID-19 organizing pneumonia in a patient without previous lung disease. Risk factors, diagnostic methods and treatment options in this group of patients are also discuss.

This paper summarizes the data from updated international protocols and guidelines for diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). The invasive and non-invasive diagnosis techniques and their combinations are briefly reviewed; the evidentiary foundations for each diagnostic option and tool are analyzed. The paper describes a customized algorithm for sequential diagnosis and differential diagnosis of patients with suspected ATTR-CM with allowance for the combination of clinical signs and diagnostic findings. Along with the awareness of primary care providers about the red flags of the disease and visualization criteria, as well as providing information to the patients about the possibility of performing therapy of ATTR amyloidosis and the risks of delayed diagnosis, the proposed algorithm enables timely patient routing and prescribing specific treatment.

The purpose of the comments is the analysis of Professor Dmitry D. Pletnev's article Hypertension (experience in analyzing its genesis) from the point of view of modern ideas about arterial hypertension. Currently, a small number of publications of Professor D.D. Pletnev, a Russian scientist and clinician, unjustly convicted in 1937, have been preserved. The small work includes not only a deep and critical analysis of the pathogenetic mechanisms of this disease, but also an assessment of diagnostic methods, as well as a detailed description of the clinical picture. The paper, published in 1935, remains relevant and of interest to clinicians and medical historians.

A combination of factors, including Western European eating habits, physical inactivity and genetic predisposition, lead to a dramatic increase in adipose tissue mass. A special place is occupied by abdominal obesity, in which there is an accumulation of adipose tissue in the mesentery of the small intestine and the omentum. Developing in conditions of visceral obesity, insulin resistance, dyslipidemia and systemic inflammation are one of the key components of the pathogenesis of type 2 diabetes mellitus, cardiovascular diseases, non-alcoholic fatty liver and pancreas disease, polycystic ovary disease, some forms of cancer (breast cancer, endometrial cancer, colonic and direct intestines). At the same time, the pathogenetic role of adipose tissue is not limited to its participation in the formation of the cardiometabolic continuum and oncogenesis. The most important role of metabolically active fat in the pathogenesis of many respiratory diseases is known, including bronchial asthma, obstructive sleep apnea and pulmonary hypertension. This paper presents an overview of current data on immunological, pathophysiological and clinical features of the phenotype of the combination of respiratory diseases with overweight and obesity.

The article reflects the potential for correcting intestinal microbiota disorders in the complex therapy of patients with COVID-19. It has been noted that the inclusion of dietary fiber in the diet contributes to protection against disruption of the integrity of the intestinal barrier and may limit bacterial translocation into the systemic circulation. The possibility of using psyllium (Mucofalk) is reflected, the action of which is realized both through its sorption, cytoprotective and anti-inflammatory properties in viral lesions of the gastrointestinal tract, and through stimulation of the own beneficial intestinal microbiota. The paper presents studies of the prospects for the use of probiotics, synbiotics in the complex therapy of patients with COVID-19. Detailed data are provided on the mechanisms of the positive effect of short-chain fatty acid preparations on reducing the severity of the disease in patients with COVID-19. It was noted that taking the drug Zacofalk leads to a significant increase in its own butyrate-producing microbiota (Faecalibacterium prausnitzii) and suppression of the growth of opportunistic flora with pro-inflammatory activity. The results of a recent study are presented showing that in patients with a mild course of COVID infection with respiratory and intestinal symptoms, the administration of Zakofalk for 30 days (3 tablets per day) led to significantly faster stool normalization (by day 7), persistent normalization of the frequency and consistency of stools by the 21st day and a significantly more pronounced regression of bloating and abdominal pain, as well as a decrease in the risk of developing post-infectious irritable bowel syndrome.

Aim - based on the clincal experience of monitoring and treatment of teenagers with Hirschsprung's disease (HD), to study clinical aspects of the disease in older children and to establish an adequate diagnostic and treatment policy. The paper is based on the analysis of the results of examination and treatment of 26 children with Hirschsprung's disease, who were first diagnosed with the disease at the age of 10 years and older. There were 19 (73.08%) boys and 7 (26.92%) girls. The following diagnostic methods were used: X-ray examination of the large intestine, ultrasonography of the abdominal organs and the large intestine, rectosigmoidoscopy, morphological examination of biopsy material, immunohistological examination for acetylcholinesterase (AChE). Nonparametric statistical methods were used due to the small sample and the prevalence of the analysis of qualitative rather than quantitative criteria. Hirschsprung's disease in older children has a latent course with long periods of functional compensation. The rectal form of pathology predominates (57.69%). The main diagnostic methods are anamnesis, features of the clinical course of the pathology, irrigoscopy, morphological examination of full-thickness rectal biopsies and immunohistochemical examination of the rectal mucosa for AChE. 84,62% of teenagers underwent one-stage surgery without postoperative complications; 15,38% of patients had indications for colostomy.

This paper reports two cases of Guillain-Barre syndrome associated with coronavirus infection COVID-19. The clinical symptoms and neurological status of patients, the data of the additional examination and the features of the prescribed therapy are described in detail. The issue of the tropicity of the SARS-CoV-2 virus to human nervous tissue and its possible ways of affecting the peripheral nervous system is discussed.

Visual object agnosia (VOA) is a loss of the ability to recognize visible objects in patients with the intact primary visual functions and in the absence of dementia. The apperceptive and associative variants of VOA are marked out. The apperceptive VOA is thought to be due to «pre-semantic» impairment of visual information processing. The associative VOA is caused by the loss of access to knowledge about the objects, and its semantic subtype is due to the disintegration of this knowledge itself. It is important to diagnose VOA and its variants in time to provide individualized approaches to medical rehabilitation of patients. Case reports of apperceptive and associative VOA in acute ischemic stroke are presented in this paper. These case reports indicate the possibility of the development of apperceptive and associative VOA in unilateral acute ischemic brain lesion. The variants of VOA can be recognized only by a detailed neuropsychological examination.

The prevalence of cervical dizziness, still not recognized by the entire medical community, not only does not become less frequent, but even increases today. This phenomenon is facilitated by the widespread computerization of our lives and, in particular, the strain on the neck when working with portable electronic equipment. Despite the fact that criteria that reliably confirming the association of dizziness with cervical pathology have not yet been defined, experimental and clinical evidence of such an association continues to accumulate. This review presents data from studies of the last few years on cervical pathology as a causative factor in some types of dizziness and vertigo. To date, the following variants of cervical vertigo are distinguished: Barre-Lieu syndrome, rotational vertebral artery syndrome, proprioceptive cervical vertigo, migraine-associated cervical vertigo. The paper considers the features of all four cervical vertigo types, as well as methods for diagnosing and the first randomized trials on the treatment of dizziness associated with the pathology of neck structures. The results of own observations of similar cases (diagnosis and treatment) are described; as well as principles of differential diagnosis of some conditions manifested by headache and dizziness in patients with various types of disorders of cervico-cranial region. The similarities of clinical presentation and pathogenetic mechanisms characteristic of skull base and neck anomalies, Meniere's syndrome and cervical vertigo are discussed. In conclusion, an assumption was made about the common origin of a whole group of the diseases associated with the cranio-cervical region.

The article is dedicated to the 350 th anniversary of the death of the Dutch anatomist, physiologist, yatrochemist and the greatest physician of the XVII century, Franciscus Sylvius (Franz de le Boe) (1614-1672). His contribution to the study of the structure of the nervous system is characterized, as well as the main scientific discoveries and achievements in building a rational system of medical science and practice. It is stated that eponym «aquaeductus Sylvii» was coined by Lorenz Heister in 1717 in his paper «De admiranda cerebelli structura».

This review addresses current issues in post-COVID syndrome with a focus on neurocognitive impairment. The results of studies on complications in patients of different ages and health statuses recovered from mild to severe COVID-19 are discussed. Current data on the pathogenetic mechanisms of the development of various post-COVID disorders are presented, including a detailed discussion of central nervous system damage. The paper summarizes data on the relationship between neurocognitive disorders and accelerated cell aging, chronic nonspecific inflammation, and reduced neuroplasticity in the central nervous system. The main pathogenetic ways to prevent COVID-related complications, including neuronal tissue damage and the prospects for managing such patients are discussed. The choice of pathogenetic therapy in patients with neurocognitive impairment in the post-COVID period is assessed. The main benefits of choline alfoscerate therapy for neurocognitive impairment in patients with post-COVID syndrome are discussed.

Constipation is one of the most common non-motor symptoms of Parkinson's disease. The pathogenetic mechanisms of constipation, diagnostic criteria, approaches to investigations and treatment are discussed in the paper.

This paper describes two cases of congenital bilateral perisylvian syndrome (CBPS), a rare disorder of late neuronal migration, which is characterized by language delay, intellectual disorders, epilepsy and bilateral perisylvian polymicrogyria. Pseudobulbar paralysis and orofacial muscles dyspraxia causing drooling and feeding difficulties are common for patients with CBPS. Communicational problems lead to low self-esteem and social maladaptation. Literature data regarding correlation between polymicrogyria topography and speech disorders and articulation impairment severity are presented. The results demonstrate the association of diffuse spreading of bilateral polymicrogyria and more severe speech disorders comparing to mild speech disorders in patients with more local polymicrogyria. Known etiology factors of this syndrome are bilateral cerebral hypoperfusion, brain damage while neuronal migration period, postmigrational vascular insults and gene mutations. Syndrome can be inherited in autosome dominant and X-linked manner. Speech apraxia with normal impressive speech, refractory epileptic seizures and status dysraphicus must be red flags for a physician regarding this syndrome. Overnight video-EEG monitoring and brain MRI confirm a thesis that this syndrome is underdiagnosed in everyday clinical practice.

Objective: This paper presents an analysis of polymorphic gene loci, the products of which are directly involved in the molecular mechanisms of regulation of neurophysiological processes., Material and Methods: The sample of subjects consisted of 128 unrelated males and females living in the European part of Russia. The study assessed the frequency of occurrence of 11 single-nucleotide substitutions located in genes encoding serotonin receptors, ciliary neurotrophic factor, uncoupling protein 2, methylenetetrahydrofolate reductase, methionine synthase, methionine synthase reductase, dipeptidyl carboxypeptidase 1, gamma-coactivator of the receptor activated by the proliferator peroxisome and neurotrophic factor of the brain. Genotyping of the samples was carried out by PCR with fluorescence detection and analysis of the polymorphism of the lengths of restriction fragments., Results: The distribution of polymorphism genotypes corresponded to the Hardy-Weinberg equilibrium with the exception of rs1801133 MTHFR (χ 2 =5.3088, p =0.0212) in which a decrease in heterozygosity was observed. These studies of minor allele distribution have no statistically significant deviations from the European population, but there are deviations from the Asian, African, and Latin American populations., Conclusion: Statistically significant correlations of allele frequencies in the study group with populations from other regions and the studies conducted in them are the basis for the inclusion of selected single-nucleotide polymorphisms in the list of a limited set of molecular genetic markers, which makes it possible to supplement the system of mental health monitoring and improve the professional training of people in extreme professions.

Common variable immunodeficiency (CVID) is one form of the primary immunodeficiencies (PIDs). CVID is characterized by variable clinical manifestations. Genetic alteration is a cause of the disease in many cases. In the current paper we described Patient N of 45 years old, who have been suffering from frequent various infections and therefore attended an immunologist and clinical geneticist. Immunoglobulins (Ig) A, M, and G deficiency was found in the patient. As a result of medical genetic counselling primary immunodeficiency has been suggested as a diagnosis. Further molecular genetic testing using clinical exome sequencing (Next Generation Sequencing method) revealed a likely-pathogenic variant c.204dupA (p.Leu69ThrfsX12, rs72553875) of TNFRSF13B gene in the patient. The gene variant was found in homozygous state. According to the international medical literature and genomic databases TNFRSF13B gene mutations lead to the CVID development and in some patients are characterized by isolated IgA deficiency and in the other group of patients can lead to decrease of IgA, IgM, and IgG. The patient had a family history of cancer and autoimmune inflammatory bowel disease (erosive-ulcerative enterocolitis). Moreover, one sibling of the patient died at the age of 3 weeks from complications of toxoplasmosis infection. The other sibling of 51 years old have been also suffering from recurrent infectious diseases. Thus, the genetic cause of the disease was identified in the proband. It has been shown that homozygosity for variant c.204dupA of TNFRSF13B gene is characterized by the deficiency of all three classes of Ig. Medical genetic counselling and modern molecular genetic methods application is an important step in management of people with signs of immunodeficiency. Such approach helps to make a diagnosis to the patient, to find an exact molecular reason of the condition, to use effective treatment, and to perform preventive measures in patient`s family.

The article describes a clinical observation of a severe course of a sporadic case of foodborne botulism in a woman at 32 weeks gestation with a successful resolution of pregnancy by independent childbirth. No adverse effects of botulism on pregnancy, delivery, and fetal development were noted. Anti-botulinum serum was administered to the patient no earlier than 96 hours from the onset of the disease. The paper analyzes the clinical picture of botulism, on the basis of which it is necessary to carry out a differential diagnosis.

Complete prosthetic surgery of the ascending aorta, aortic arch branches, and descending aorta in patients with aortic arch aneurysm, study and demonstration the possibility of the "elephant trunk" method. The paper describes the technology and demonstrates the results of the first 29 operations of ascending aorta, aortic arch, aortic arch branches and descending thoracic aortic prostheses performed by the staff of the Department of Aortic Pathologies of the Amusov State Institute during 2016-2020. All patients, underwent elephant trunk prosthesis surgery of the ascending aorta, aortic arch, aortic arch branches, and descending thoracic aorta as the first stage of reconstruction of aortic arch pathology. Most of the patients, except for three, underwent the second stage of surgery, endoprosthesis of the aortic arch and descending thoracic aorta through a vascular stent. In case of an aortic arch aneurysm or disruption of the anatomical integrity of blood vessels, restoration of the anatomical integrity of the aortic arch and aortic arch blood vessels or prosthesis of blood vessels in this basin can be performed through "elephant trunk" surgery. Optimization and improvement of preoperative diagnostics, surgical techniques, methods of protection of the brain, spinal cord and visceral organs, the use of hybrid / endovascular techniques allows treatment in case of complex damage to the ascending arch and descending thoracic aorta. The first completely satisfactory results of the performed operations were obtained, the hospital lethality was demonstrated within 10.3%.

The virologists' attention to bats (Сhiroptera) changed in the late 20th century as the concept of emerging infections grew in popularity. Since the beginning of the COVID-19 pandemic, the number of publications on bat viruses has increased profoundly.History of the problem; biodiversity of Chiroptera and related viruses; medical and veterinary significance of some viral genera and subgenera (Lyssavirus, Henipavirus, Marburgvirus, Ebolavirus, Sarbecovirus, Merbecovirus), as well as problems of bat protection, are addressed in a concise form. Literature search was carried out in electronic databases, mainly for the period of 2000-2021. Publications in Russian that are poorly represented in English-language reviews are also included. The purpose of the review is to substantiate the importance of an interdisciplinary approach in the context of increased interest in the study of viral infections in bats. This review was written for researchers who have not previously dealt with this problem.Since the beginning of this century, the number of known virus species associated with bats has increased by an order of magnitude (>200). The families Rhabdoviridae, Coronaviridae, Paramyxoviridae are in the first ranks according to the number of findings, and the highest diversity of viruses has been established for the families Vespertilionidae, Pteropodidae, Molossidae. Interdisciplinary cooperation positively influences the efficiency, biological safety and practical significance of the ongoing research. The best results were achieved by multidisciplinary teams with good cross-training in several specialties. Many papers emphasize the need to balance health and conservation interests.The analysis of scientific publications indicates a change in research approaches in this area: from collecting individual facts within the framework of narrow specialties to a comprehensive assessment of new knowledge from ecological, evolutionary and socio-economic positions. Results of the research emphasize the need to maintain complex approaches addressing public health needs and environmental protection. The importance of bat-borne viral infections determines the necessity for correction and interdepartmental coordination of scientific research and surveillance of wildlife zoonoses in the Russian Federation.

The paper summarizes the most important aspects of modern treatment of patients with pulmonary arterial hypertension (PAH): the goals of therapy are indicated, the issues of risk stratification of PAH progression/mortality, the place of combination specific therapy and switching strategies are considered, as well as new promising approaches to therapy; features of the course of the new coronavirus infection COVID-19 in this category of patients are discussed.

Due to the new coronavirus infection pandemic, the global scientific community has been forced to change the direction of the most research, focusing on vaccine development as well as the search for new antiviral drugs to treat COVID-19. The choice of experimental models, timeframe and approaches for evaluating drugs and vaccines under development is crucial for the development of effective measures to prevent and control this disease.The purpose of this review was to summarize the relevant data concerning the susceptibility of laboratory animals to SARS-CoV-2. This paper describes the most virus-susceptible animal species that can be used to reproduce coronavirus infection, stressing the main advantages and disadvantages of each of them.According to the latest data, small rodents (Rodentia) and non-human primates (Strepsirrhini) are commonly used in the scientific community to model coronavirus infection. The viral load in the upper and lower parts of the respiratory system, clinical symptoms of infection (weight loss, body temperature and general health status), pathomorphological picture in target organs and the production of antibodies after infection are considered to the main markers of pathology. Despite the vast amount of data, none of the described models of SARS-CoV-2 infection may be considered a gold standard, since they do not reproduce all spectrum of morphological and pathogenetic mechanisms of infection, and do not fully reflect the clinical picture observed in patients in human population.Based on the analyzed literature data, we suppose that Syrian hamster (Mesocricetus auratus) and mice (Muridae) expressing the angiotensin converting enzyme receptor 2 (ACE2) are the most suitable animal species for their use in experiments with SARS-CoV-2 infection. The development of neutralizing antibodies makes it possible to evaluate the efficacy of vaccines, while the course and severity of symptoms infection makes the use of mice and hamsters especially popular for screening pharmacological substances with antiviral mechanism of action, when their administration can prevent or slow the disease progression.

Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder characterised by lack of pubertal development and infertility, due to deficient production, secretion or action of gonadotropin-releasing hormone (GnRH). Clinically, there are variants of CHH with hypo-/anosmia (Kalman syndrome) and normosmic hypogonadotropic hypogonadism. Given a  growing list of gene mutations accounting for CHH, the application of next generation sequencing (NGS) comprises an excellent molecular diagnostic approach because it enables the simultaneous evaluation of many genes. Biallelic mutations in GNRHR gene lead to the development of hypogonadotropic hypogonadism with normosmia. In this paper, we describe 16 patients with proven GnRH resistance and estimate the frequency of pathogenic variants in the GNRHR gene in the Russian population.

Oral manifestations of HIV infection are diverse and not still not completely studied. HIV-associated diseases can occur as the first symptoms of infection, these are characterized by high frequency, clinical polymorphism and pronounced course. Periodontal aspects are also neglected in the literature. No papers on the condition of different areas of the oral mucosa, tongue and periodontium where they were studied simultaneously and according to various criteria have been found in the available literature. The objective of the research is to evaluate the condition of periodontium and the oral mucosa in different parts of the oral cavity in HIV-positive patients. Total number of the HIV-positive patients observed was 90, among them 81 males and 9 females between the age range of 24-62. An average age of the patients was 45.2±8.34, with male patients prevailing (p<0.001). HIV infection was diagnosed by Western-blot reaction. Clinical examination as well as probing and determination of the pocket depth by means of the periodontal probe was carried out to assess the health status of the oral cavity. Periodontal indices were also determined. It has been found that immunocompromised condition due to HIV infection contributes to the oral mucosa lesions. Namely, coated tongue was observed in 100% of cases, the oral mucosa relief impairment was seen in 75.6% of cases, lip cracks of different location and bright red color of the mucous membrane were observed in 73.3% and 82.2%, respectively (р<0.001). Examination of the tongue revealed the symptoms which were not found in the control group, such as tongue coating - in 100% (90 patients observed), epithelial desquamation foci - in 54.4% (49) (p<0.001). Inflammatory diseases of periodontium, particularly catarrhal and hypertrophic gingivitis and periodontitis of moderate severity were also revealed.

Acute and chronic thyroid diseases are the most frequently detected disorders being second only to diabetes mellitus.The World Health Organization points out that thyroid diseases' incidence tends to grow every year. The present paper consists of clinical practice guidelines that consider etiology, clinical course, diagnostics and treatment of acute and chronic inflammatory thyroid diseases (except those of autoimmune type).The clinical practice guidelines provide an important working tool for clinicians including specialty physicians and medical experts. Containing structured and concise information on the specific nosology, diagnostic methods and treatment tips these guidelines allow medical specialists to quickly resolve difficulties and choose the most efficient and personalized treatment (following strict principles of evidence-based medicine at the same time).The clinical practice guidelines were drawn up by highly-skilled professional team of specialty physicians approved by the Expert Council of Russian Federation's Health Department. These guidelines contain the most complete and up-to-date information required to diagnose acute and chronic thyroiditis, provide patient care and treatment.The working group publishes the present paper in the professional journal dealing with endocrinology topics to improve healthcare quality and refine treatment of acute and chronic thyroiditis (autoimmune thyroiditis excluded). It is advisable to acquaint as many endocrinology and general (family) medicine specialists as possible with the full text of these clinical guidelines.

The review summarizes the current literature data on the inherited metabolic disorder of branched-chain amino acids - methylmalonic aciduria, characterized by high mortality, acute onset and crisis course. The paper presents the molecular genetic characteristics of the known thirteen different genes (responsible for the synthesis of methylmalonyl-CoA mutase, methylmalonyl-CoA epimerase and vitamin B12 metabolism), mutations of which lead to the development of methylmalonic aciduria. The current knowledge about the potential role of organic acids and their derivatives in the development of metabolic decompensation, toxic damage to the nervous system and internal organs is presented. Early diagnosis by tandem mass spectrometry is extremely important, since timely treatment started (diet therapy, the use of hydroxycobalamin in the B12-dependent form) prevent an unfavorable outcome and allow a high degree of rehabilitation for children with this pathology. Moreover, the identification of the primary molecular genetic defect makes it possible to adjust the patient management tactics and to carry out further prenatal diagnosis of the pathology in subsequent pregnancies.

Background: Primary hyperparathyroidism (PGPT) is an increase in the secretory activity of the parathyroid glands (OSH), due to their tumor or hyperplastic changes. Due to the lack of an effective alternative to the treatment of PGPT, the surgical method is still the only correct tactical solution for the management of patients with an established diagnosis of PGPT. The paper presents the long-term results and assessment of the quality of life of patients who underwent surgical treatment from standard and small access. The results obtained showed the promise of a sparing approach to the treatment of PGPT caused by LV adenoma., Aim: To study the effectiveness of surgical treatment of patients with PGPT based on the assessment of the quality of life of patients who underwent parathyroidectomy from standard and small access., Materials and Methods: A retrospective study of the quality of life of patients with PGPT after surgical treatment was conducted using the SF-36 questionnaire and the linear analog scale (LAS). Statistical data processing is performed in the R programming language using the FMSB package. The quantitative parameters were presented as median (Median) and interquartile range (25th (1st Qu) - lower quartile and 75th (3rd Qu ) - upper quartile). As a nonparametric statistical criterion, the Mann-Whitney U-test was used, on the basis of which the p-value was calculated. The calculated data of the research results are presented in graphical form - in the form of bar charts, spider plot and barplot., Results: This study involved 264 patients. The patients were divided into 2 groups: GR1 - patients operated from the Kocher access with mandatory revision of all 4 OSH, GR2 - patients who received surgical treatment from the small access with the removal of the altered OSH, without revision of the remaining OSH. When analyzing the quality of life of patients before surgery, there were no statistically significant differences in the groups in terms of PF (Physical Functioning) and VT (Vitality). Small-access parathyroidectomy (patients with GR 2) significantly improved the quality of life in the GH (General Health) and VT (Vitality) domains. The analysis of LAS before surgery between the groups showed no statistically significant differences, while after surgical treatment, the indicators on the linear analog scale differ in the direction of improvement in GR2., Conclusion: The results obtained in the course of the study showed the promise of a gentle approach to the treatment of PGPT caused by LV adenoma, which is reflected in higher quality of life indicators.

Objective: Neuroprotective and nootropic drugs often exhibit complementary, «synergistic» effects, the consideration of which is important for choosing the most effective and safe drug combinations., Material and Methods: Chemoinformatic analysis of vinpocetine, piracetam and cinnarizine on neuron cultures, on model organisms (mice, rats) based on modern data mining and machine learning methods., Results: The paper presents the results of the chemoreactom analysis of vinpocetine, piracetam, and cinnarizine. Estimates of various biological activities of molecules on neuronal cultures, on model organisms (mice, rats) and estimates of modulation of the activity of target proteins in rats and humans were obtained. The data obtained made it possible to quantify the value of the synergism score for the combination «vinpocetine + piracetam» (54 points) compared with the combination «piracetam + cinnarizine» (25 points)., Conclusions: The combination of «vinpocetine + piracetam» in the fixed combination (Vinpotropil) is thus more preferable for combined use than for the combination of «piracetam + cinnarizine».

The paper addresses associations between sleep disorders and emotional and behavioral disturbances in children. These associations are considered in a view of commonly found co-occurrences of sleep problems, signs of anxiety and depression, oppositional-defiant behavior, and increased aggressiveness. The authors put forward a conception of reciprocal influences of these disturbances and provide information on potential physiological mechanisms responsible for associations between sleep problems and emotional and behavioral disturbances in children. Attention is drawn to hypothalamus-hypophysis-adrenal axis activation, serotonergic and aminergic systems imbalance, impaired melatonin and orexins production. Possibility of an existing pattern encompassing sleep problems, emotional and behavioral disturbances is discussed. Practical recommendations aimed at timely identification and treatment of the mentioned disorders are suggested.