Alzheimer’s is a global disease (AD). The most important pathogenesis of AD is the increase in the amyloid-β protein (Aβ) deposition, and abnormal phosphorylation aggregation of the microtubule-associated protein tau. Many etiological factors are implicated in the production of AD such as age, genetics, lifestyle, environmental factors, and gut microbiota (GM). Dysregulation of GM contributes to AD pathogenesis and cognitive impairment via several mechanisms, including Aβ and Tau protein aggregation, production of neurotransmitters and metabolites, immune dysregulation, neuroinflammation, blood-brain barrier disruption, oxidative stress, and leaky gut.
Sex differences might be an important factor for AD pathogenesis. About 75 % of AD patients are females. The higher prevalence of AD in females is due to their genetics, brain structure, and function, estrogen, lifestyle factors (e.g., education, occupation, exercise, and sleep), and incidences of infection and inflammations. Because women live longer than men do, they are more likely to get AD.
This article discusses the role of the GM and sex differences in AD. It begins with an overview of the gut-microbiota axis and sex differences in AD. It discusses promising therapeutic strategies for AD targeting GM.

Nowadays non-alcoholic fatty liver disease (NAFLD) and sarcopenia are actually considered as one of the pathological condition with involvement into development of pathology of liver and skeletal muscles. Scientists of different countries found that sarcopenia is associated with insulin resistance and skeletal muscle atrophy as an insulin target organ. Spredly known many cytokines of inflammation with variable affection of skeletal muscle proteins, low level of adiponectin, decreased insulin sensitivity, oxidative stress with activation of catabolism leading to muscle atrophy are involved into complicated pathogenesis of NAFLD. Progressive sarcopenia associated with NAFLD is prognostic factor and can increase the risk of mortality. Sarcopenia, which due to decreased skeletal muscle mass and increased visceral fat, very often provokes development of sarcopenic obesity and NAFLD. Hyperammonemia, abnormal intestinal microbiota, lipid factors also contribute to the development of sarcopenia in patients with NAFLD. Given the common pathogenetic mechanisms indicating a bidirectional relationship between sarcopenia and NAFLD, a multidisciplinary approach to the management of patients with NAFLD and sarcopenia could be the most optimal. Modern strategies are aimed at early diagnosis of NAFLD with sarcopenia, optimizing the lifestyle of these patients, searching for effective drugs, personalizing treatment and prevention of the progression of these diseases and their complications.

Objective. To evaluate the content of intercellular adhesion molecules: ICAM-1, ICAM-2, ICAM-3, NCAM, VCAM-1, PECAM-1, E-sel, P-sel, EpCAM, L-sel in patients with COVID-19-associated lung damage and to identify the relationship between their concentration and severity the flow of the process. Materials and methods. The study included 200 patients after suffering COVID-19-associated lung damage 1 month after discharge from Chita monostationals. The subjects were divided into groups of 50 people, depending on the degree of lung damage according to the results of computed tomography: Group 1 (CT-1), median age was 51.5 [50.5; 54.8]; Group 2 (CT-2), median age 57.0 [53.1; 57.0]; group 3 (CT-3), median age 52.5 [51.9; 55.0]; 4th group (CT-4), median 55.0 [53.2; 56.4]. The control group included 56 relatively healthy individuals who had not previously had coronavirus infection and other acute respiratory diseases in the last 3 months, the median age was 55.0 [51.1; 55.0]. All the study groups were comparable in gender and age. The content of intercellular adhesion molecules in blood serum was determined by immunochemical analysis. Results. The study revealed an increased content of intercellular adhesion molecules (MMA) (ICAM-1, ICAM-2, ICAM-3, NCAM, VCAM-1, PECAM-1, E-sel, P-sel, EpCAM, L-sel) in the studied groups of patients with COVID-19-associated lung damage in comparison with the control group. Differences were found between groups of patients with different levels of lung damage according to CT data, when examining some intercellular adhesion molecules. Conclusion. According to the results of the work carried out, it was revealed that after a coronavirus infection complicated by lung damage, an increase in the concentration of intercellular adhesion molecules in the blood is observed — representatives of all the studied superfamilies. An increase in the levels of intercellular adhesion molecules in the studied patients reflects the presence of endotheliosis and correlates with the severity of lung tissue damage, including during the period of convalescence.

Relevance. Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome occurring with a frequency of 1:3164 of the world’s population. The disease is characterized by severe clinical manifestations such as multiple cutaneous and subcutaneous tumors, plexiform neurofibromas, skeletal abnormalities, cognitive disorders and various complications. The aim of the study. To determine the frequency of NF1 in the Republic of Bashkortostan and its dynamics, clinical features of NF1 to improve organizational and therapeutic and diagnostic approaches in providing medical care to patients with NF1.Material and methods. A clinical and epidemiological study of NF1 patients in the Republic of Bashkortostan and a comparative analysis with data for 2009 and 2021 were conducted. Results. In the Republic of Bashkortostan, 544 patients with NF1 from 433 families aged 1 to 85 years (average age 30 years and 7 months) were registered, the incidence rate is 1:7407 people. Pigment spots were identified in all patients, cutaneous and subcutaneous neurofibromas in 58 %, plexiform neurofibromas in 7 %, scoliosis in 17.4 %. Learning difficulties were identified in 14 %, epilepsy in 3.7 %, hydrocephalus in 4 %, optic nerve gliomas in 6 %, and brain tumors in 4 % of NF1 patients from the republic. Discussion. A comparative analysis of the characteristics of NF1 in patients from the Republic of Bashkortostan with global data showed a significantly rarer detection of neurofibromas, Lisch nodules, optic nerve gliomas, intellectual disabilities and psychological disorders. The number of patients with NF1 in the republic has increased by 2.3 times in 15 years and by 35 % in the last 3 years. Moreover, 4 patients with plexiform neurofibromas are receiving a mitogen-activated protein kinase inhibitor, which has proven its effectiveness. Conclusion. The obtained results indicate an increase in the number of registered cases of NF1 in recent years, but the need for a multidisciplinary approach in the study of patients due to the reliably low frequency of registration of characteristic symptoms of the disease.

Aim of the work: to explore the possible relation between macrovascular disease especially atherosclerosis and microcirculation abnormalities in patients with T2DM and, to assess any relationship between blood glucose level, microvascular and macrovascular affection. Patients and methods: the study recruited 150 participants; 100 patients with T2DM and 50 controls. All participants underwent history taking, clinical examination, biochemistry testing including HBA1c, FPG, 2h-PG, TG, TC, HDL, and LDL. Nailfold video capillaroscopy (NVC) was performed to evaluate morphology of the nailfold capillaries, arterial and venous limb diameter, alteration in Capillary length and loop diameter, presence or absence of capillary hemorrhage, extravasation, scarring, scanty and large capillaries. To score these alterations, a semi-quantitative rating scale (0–3) was used. Carotid duplex was done to all participants to measure the intima media thickness in the common carotid artery (CIMT). Results: Subjects with T2DM showed significantly increased CIMT when compared with controls. There were a significantly higher frequencies of abnormal capillary morphology, hemorrhage, scarring and scanty capillaries, Modified NVC score>1 in T2DM. In comparison to the control group, they also exhibited noticeably greater rates of extravasation, branching, crossed, and corkscrew-shaped capillaries, larger loops, and decreased capillary length. There was significantly higher left and right CIMT in the group of diabetics with Modified NVC score >1. Conclusion: A significant relationship was found between atherosclerosis and microcirculation abnormalities. Videocapilloroscopy could be used to assess microcirculatory abnormalities before detection of atherosclerosis by carotid duplex.

Aim of investigation. To study the prognostic significance of clinical and laboratory markers of liver pathology, including components of the matrix metalloproteinase (MMP) system, to identify moderate/significant activity in chronic liver diseases (CLD). Materials and methods. 76 patients with CLD of viral or alcoholic etiology aged from 18 to 64 years were examined. Minimal (histological activity index — HAI 1-3 points), minor (HAI 4-8 points), moderate (HAI 9-12 points) and significant morphological activity (HAI more than 12 points) were detected in 19 (25.0 %), 34 (44.7 %), 14 (18.4 %) and 9 (11.9 %) of cases, respectively. Enzyme immunoassay was used to determine the blood levels of MMP-1, MMP-9, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), and the of TIMP-1/MMP-1, TIMP-1/MMP-9 was calculated. Results. According to multivariate logistic regression data, moderate/significant histological activity of CLD was associated with γ-glutamyltranspeptidase (GGT) (odds ratio (OR) 1.016; 95 % confidence interval (CI) (1.006-1.024), p=0.001), international normalized ratio (INR) (OR 1.079; 95 % CI (1.028-1.132), p=0.002), and TIMP-1/MMP- 9 ratio (OR 0.554; 95 % CI (0.380-0.809), p=0.002). The combination of these parameters had sensitivity of 82.6 %, specificity of 92.5 % and accuracy of 89.5 % in detecting HAI of 9 or more points. Conclusion. The increased values of GGT and INR, as well as a reduced ratio of TIMP-1/MMP-9, are independent risk factors for moderate/significant histological activity in CLD, due to their participation in the processes of hepatic inflammation.

Close attention to the problem of amyloid cardiomyopathy in recent years has been caused by a significant increase in the disease detection simultaneously with increased sensitivity and specificity of imaging methods used in cardiological practice, along with the emergence of new promising diagnostic methods and specific therapy. The choice of treatment tactics for systemic amyloidosis directly depends on the results of typing of amyloidogenic proteins, which became possible due to the development of proteomics based on mass spectrometry. To date, it has been proven that amyloid cardiomyopathy is an important and often undiagnosed cause of chronic heart failure and cardiac arrhythmias, especially in the elderly. There are more than 15 types of precursor proteins capable of causing systemic amyloidosis, but only 2 of them accumulate in the interstitium of the heart: light chains of clonal immunoglobulin (AL) and tetrameric protein transthyretin (TTR). The significant prevalence of wild-type genetic transthyretin amyloidosis (ATTRwt), formerly referred to as senile systemic amyloidosis, is indicated by the following figures: in 13 % of patients hospitalized for decompensation of chronic heart failure with preserved left ventricular ejection fraction, transthyretin amyloid cardiomyopathy was a diagnostic finding, among patients over 80 years of age, this pathology is detected post mortem in 20-25 % of pathoanatomic reports, and in 37 % of cases in the long-lived group (patients over 97 years of age). Even with early diagnosis of ATTR-amyloidosis, the life expectancy from the moment the first symptoms appear is 10-12 years, as the disease progresses irreversibly, leading to disability due to severe heart damage and polyneuropathy. The late diagnosis of systemic amyloidosis is due to the low awareness of primary care physicians, the presence of comorbidity in elderly patients, the absence of specific symptoms of the disease and available diagnostic screening methods, and determines an unfavorable prognosis of this disease, especially with the formation of amyloid cardiomyopathy. The relevance of this topic is due to the need to improve diagnostic algorithms and reduce the time for primary diagnosis of amyloid cardiomyopathy in order to improve the prognosis of the disease.
We have described a clinical case of an elderly patient with a torpid course of progressive decompensation of congestive heart failure, which ended fatally on the 3rd day of hospitalization. Echocardiographic criteria brought us closer to the diagnosis of amyloid cardiomyopathy, but pathoanatomic studies have confirmed the diagnosis of systemic amyloidosis with predominant heart damage.

Chronic heart failure with preserved ejection fraction (HFpEF) is a complex, heterogeneous, multi-organ systemic syndrome characterized by significant morbidity and mortality. Currently, it has acquired the character of an epidemic of the 21st century. The clinical observation describes a typical story of an elderly patient suffering from coronary artery disease (CAD), dyslipidemia, atherosclerosis of the brachiocephalic arteries against the background of arterial hypertension (AH), obesity, type 2 diabetes mellitus (DM), complicated by diabetic retinopathy, polyneuropathy, nephropathy with development of chronic kidney disease (CKD) and HFpEF. The condition was aggravated by the presence of chronic pyelonephritis of a single kidney (right nephrectomy for renal abscess in 2013), bronchial asthma. The limitations of modern scales for determining the pre-test probability of HFpEF and low natriuretic peptide levels are demonstrated. Comorbidity, poorly controlled hypertension, diabetes, low adherence to therapy led to the development of acute vascular accident, then, repeated cerebrovascular accident — to a fatal outcome. Histologically, perivascular and interstitial sclerosis in the myocardium and epicardium was detected, which is the basis of diastolic dysfunction in HFpEF.
A clinical example reflects the difficulties of verification of HFpEF-diagnosis, as well as the mutual pathogenetic influence of concomitant pathology, which can lead to an unfavorable outcome if recommendations are not followed.