Development Of Pathology Research Articles

CAUSES OF MORBIDITY AND MORTALITY IN STELLER SEA LIONS (EUMETOPIAS JUBATUS) UNDER PROFESSIONAL CARE IN NORTH AMERICAN AQUARIUMS FROM 1979 TO 2021.

To date, published comprehensive pathology investigations documented in Steller sea lions (SSL; Eumetopias jubatus) are from free-ranging populations, whereas health data from those under professional care in aquariums are currently lacking. A retrospective review of gross and histopathologic reports of SSL under human care in North American aquariums from 1979 to 2021 (n = 20) was performed. Associations between age, sex, or birth origin (born in aquariums versus the wild) with cause of death (COD) and comorbidities were explored. Age was significantly associated with development of endocrine organ pathology (P = 0.011). A relationship between age and both cardiovascular and ocular disease was suggested by the data, but did not reach significance (P = 0.058). Ocular disease was significantly associated with being born in aquariums (P = 0.022). The most common COD was neoplasia (n = 10), which was significantly associated with aged animals (P = 0.038). Less frequent COD included sepsis (confirmed, n = 2; suspected, n = 3), cardiomyopathy (n = 1), clostridial enteritis (n = 1), Sarcocystis spp. (n = 1), complication secondary to sedation (n = 1), and unknown (n = 1). This is the first report documenting the high prevalence of neoplasia in SSL, with tumors found incidentally in three individuals, frequent metastasis (10/13, 77%), and many cases of multiple primary malignancies (6/13, 46%). These data expand upon the current understanding of disease in SSL, highlight this species' predisposition to neoplasia with increasing longevity, and underscore the need for heightened screening in aged animals, which may ultimately serve to elevate the care of SSL under professional care in aquariums.

Association Between Intracranial Aneurysms and Genes

Ruptured intracranial aneurysm(IA) leads to aneurysmal subarachnoid hemorrhage(aSAH), which is the most severe type of stroke. Besides age, sex, and alcohol consumption, family history is considered an important risk factor. Approximately 5% of the Japanese population is affected by unruptured cerebral aneurysms. However, their developmental processes and pathologies remain unclear. Familial cerebral aneurysms account for 10% of all cerebral aneurysm cases, and somatic gene mutations are believed to be involved in their development. This review summarizes the recent findings from family-based, genome-wide association, sequencing, and somatic gene mutation studies on IA.

The Role of Mast Cell-Neuron Tandem in the Regulation of Cardiac Function in Cardiovascular Pathologies

This review is consisted of new data about participation of mast cells (MCs) in the regulation of cardiac function in the development of some cardiovascular pathologies. In norm the number of MCs in the heart is very small compared to their number in barrier tissues. They are responsible for homeostasis of cardiac tissue and ensuring the interaction of the organ with the nervous and endocrine systems throughout the life of the organism. Pathological processes in the heart are accompanied by the development of inflammation reaction. MCs fulfil a significant role in the all stages of inflammation. The number of MCs significantly increases against the background of myocardial infarction development, fibrotic heart disease and vascular atherosclerosis. Their contribution to the pathogenesis of the disease is ambiguous, because on the one hand it is aimed at tissue adaptation to damage, and on the other hand - avalanche-like synthesis and release of mediators from activated MCs aggravates the course of the process. As a result, MCs change their secretory profile, interfere in the realization of cardiac functions against the background of inflammation, but at the same time modulate afferent information flow from the heart and efferent influences of the nervous system. The coordinated work of the system loses its stability, which can lead to severe consequences for the vital activity of the whole organism. The analysis of the current state of the problem indicates that the heart activity depends on the functional state of MCs, their complex interaction with the nervous system both in the norm and, especially, against the background of pathological processes development.

Investigation of pulmonary artery and circulating endothelin-1 expression in dogs with pulmonary hypertension secondary to myxomatous mitral valve disease.

Pulmonary hypertension (PH) is a condition characterized by abnormally elevated pressure in the pulmonary vasculature. It is a common complication of myxomatous mitral valve disease (MMVD) in dogs. Several vasoactive substances, including endothelin-1 (ET-1), have been suggested to contribute to pathological changes in the pulmonary arteries of patients with PH. This study aimed to examine the local and systemic expression of ET-1 in dogs with PH secondary to MMVD. Lung tissues were collected from 20 client-owned dogs during the first stage of the study and divided into three groups: normal dogs (n = 5), MMVD dogs (n = 8), and MMVD+PH dogs (n = 7). The expression of ET-1 and endothelin A receptor (ETAR) in the pulmonary arteries was determined using immunohistochemistry. Blood samples were collected from 61 client-owned dogs for the second stage of the study and divided into three groups: normal (n = 22), MMVD (n = 20), and MMVD+PH (n = 19). Plasma ET-1 concentration was measured using a sandwich enzyme-linked immunosorbent assay. There was no difference in ET-1 and ETAR expression in the pulmonary arteries among the three groups. Similarly, there was no difference in the plasma ET-1 concentration between the groups. In addition, no correlation was found between the immunohistochemical expression of ET-1 and ETAR and the thickness of the pulmonary arteries or between the plasma ET-1 level and echocardiographic variables. The lack of difference in the expression of ET-1 and ETAR in the pulmonary arteries and in the circulating ET-1 concentration among the studied groups suggests that ET-1 may not be related to the pathological development of PH secondary to MMVD in dogs. Due to the small sample size in this study, further research is needed to confirm these findings.

Apolipoprotein E in Alzheimer's Disease: Focus on Synaptic Function and Therapeutic Strategy.

Synaptic dysfunction is a critical pathological feature in the early phase of Alzheimer's disease (AD) that precedes typical hallmarks of AD, including beta-amyloid (Aβ) plaques and neurofibrillary tangles. However, the underlying mechanism of synaptic dysfunction remains incompletely defined. Apolipoprotein E (APOE) has been shown to play a key role in the pathogenesis of AD, and the ε4 allele of APOE remains the strongest genetic risk factor for sporadic AD. Itiswidelyrecognizedthat APOE4 accelerates the development of Aβ andtau pathology in AD. Recent studies have indicated that APOE affects synaptic function through a variety of pathways. Here, we summarize the mechanism of modulating synapses by various APOE isoforms and demonstrate the therapeutic potential by targeting APOE4 for AD treatment.

PRIMARY PREVENTION OF CARDIOVASCULAR DISEASES AND WAYS OF IMPROVING RISK ASSESSMENT OF THEIR DEVELOPMENT IN CLINICAL PRACTICE

Introduction. Cardiovascular diseases are a global problem and one of the main causes of death worldwide. Aim. To highlight and analyze modern approaches to the use in routine practice of risk factors for the development of cardiovascular pathology, which is appropriate for further clinical decision-making based on a meta-analysis of literary sources, clinical guidelines and the results of multicenter studies. Materials and methods. The search and selection of publications, systematic reviews and current recommendations is carried out using PubMed and Google Scholar databases, their detailed analysis and description. Results and discussion. The article provides data on primary prevention, which includes assessment and implementation of measures to reduce the overall risk of developing cardiovascular diseases in patients. Methods for assessing individual total or relative risk (use of SCORE and SCORE 2 scales, various risk calculators, etc.) taking into account the level of cholesterol and its various fractions are given. The importance of taking into account additional independent risk factors for the development of cardiovascular diseases is also considered. The possibility of taking into account the level of lipoprotein (a), high-density lipoprotein, and high-sensitivity C-reactive protein to improve the accuracy of predicting cardiovascular risk is discussed. Attention is paid to the possibility of using such "non-metabolic" factors as environmental pollution, psychosocial stress and stressful conditions, sleep disorders and obstructive sleep apnea syndrome, family history and genetic factors to change the risk category. Conclusions. The results of the conducted analysis prove that the given methods and importance of detection of subclinical atherosclerosis especially in patients with low or medium (marginal) cardiovascular risk. The use of both primary and secondary risk factors may be appropriate to inform decisions about changes in the calculated risk of such patients, the use and effectiveness of specific cardiac treatments, and the implementation of preventive measures such as statin therapy.

Evaluation of the effectiveness of a hyperlipidic-hyperglycemic diet in inducing weight gain and dyslipidemia in wistar rats

Hyperlipidic and hyperglycemic diets, called cafeteria diets, are important factors that favor the development of pathologies and comorbidities such as obesity, type 2 diabetes mellitus, neoplasms, and cardiovascular diseases. Thus, their use in experimental studies that aim to understand the factors that encompass the pathophysiology and treatment of obesity and the comorbidities involved has increased in recent years. Taking that into consideration, the aim of this study was to analyze the effectiveness of a high-fat-hyperglycemic (HHD) diet in inducing weight gain and dyslipidemia in Wistar rats. In this study, 22 rats were divided into 2 groups, and exposed to standard and high-fat-hyperglycemic diets for 11 weeks. After that, euthanasia was carried out along with collection of blood samples for analysis of the following parameters of the lipid profile: triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-c), high-density lipoprotein (HDL-c), and TG/HDL-c ratio. A more expressive weight gain was found in the rats that received HHD (p=0.006) in relation to the group maintained on the standard diet. Furthermore, no statistically detected alterations were found in the levels of TG, TC, LDL-c, HDL-c, and TG-HDL-c ratio. Analysis of the results indicated that HHD was effective in inducing weight gain in rats. However, there was no significant influence on the lipid profile.

Steroid profiling in human primary teeth via liquid chromatography-tandem mass spectrometry for long-term retrospective steroid measurement.

Steroid hormones are important modulators of many physiological processes, and measurements of steroids in blood, saliva, and urine matrices are widely used to assess endocrine pathologies and stress. However, these matrices cannot be used to retrospectively assess early-life stress and developmental endocrine pathologies, because they do not integrate steroid levels over the long term. A novel biological matrix in which to measure steroids is primary teeth (or "baby teeth"). Primary teeth develop early in life and accumulate various endogenous molecules during their gradual formation. Here, we developed and validated the first assay to measure steroids in human primary teeth using liquid chromatography-tandem spectrometry (LC-MS/MS). Our assay is highly sensitive, specific, accurate, and precise. It allows for the simultaneous quantification of 17 steroids in primary teeth (16 of which have not been examined previously in primary teeth). Overall, steroid levels in primary teeth were relatively low, and 8 steroids were quantifiable. Levels of dehydroepiandrosterone, cortisol, and progesterone were the highest of the 17 steroids examined. Next, we used this assay to perform steroid profiling in primary teeth from males and females. The same 8 steroids were quantifiable, and no sex differences were found. Levels of androgens (androstenedione and testosterone) were positively correlated, and levels of glucocorticoids (cortisol, cortisone, corticosterone, 11-dehydrocorticosterone) were also positively correlated. These data demonstrate that multiple steroids can be quantified by LC-MS/MS in human primary teeth, and this method potentially provides a powerful new way to retrospectively assess early-life stress and developmental endocrine pathologies.

Persistent Post COVID-19 Endothelial Dysfunction and Oxidative Stress in Women.

The assessment of endothelial dysfunction and free radical homeostasis parameters were performed in 92 women, aged 45 to 69 years, divided into the following groups: women without COVID-19 (unvaccinated, no antibodies, control); women with acute phase of COVID-19 infection (main group, COVID-19+); 12 months post COVID-19+; women with anti-SARS-CoV-2 IgG with no symptoms of COVID-19 in the last 12 months (asymptomatic COVID-19). Compared to the control, patients of the main group had lower glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities, decreased advanced glycation end products (AGEs) level, higher glutathione reductase (GR) activity, and higher glutathione S transferases pi (GSTpi), thiobarbituric acid reactants (TBARs), endothelin (END)-1, and END-2 concentrations (all p ≤ 0.05). The group with asymptomatic COVID-19 had lower 8-OHdG and oxidized glutathione (GSSG) levels, decreased total antioxidant status (TAS), and higher reduced glutathione (GSH) and GSH/GSSG levels (all p ≤ 0.05). In the group COVID-19+, as compared to the group without clinical symptoms, we detected lower GPx and SOD activities, decreased AGEs concentration, a higher TAS, and greater GR activity and GSTpi and TBARs concentrations (all p ≤ 0.05). The high content of lipid peroxidation products 12 months post COVID-19+, despite decrease in ENDs, indicates long-term changes in free radical homeostasis. These data indicate increased levels of lipid peroxidation production contribute, in part, to the development of free radical related pathologies including long-term post COVID syndrome.

Heparan sulfate proteoglycans in pathological protein aggregation and brain functionality

Proteoglycans are highly specialized proteins with specific interactive modules in their core proteins, allowing them to engage with a diverse range of cellular and structural proteins, contributing to many varied roles in cell processes. This review examines the roles of heparan sulfate (HS) proteoglycans (HSPGs) in the assembly of pathological protein aggregates in brain tissues, which negatively impact cognitive brain function. While HSPGs play roles in normal brain development, they also contribute to the abnormal accumulation and persistence of protein aggregates in Alzheimer’s and Parkinson’s diseases (AD and PD), prolonging their neurotoxic effects. HSPG-mediated effects on the innate immune system may also contribute to the development of neuroinflammation and pathogenesis of neurodegenerative changes in the central nervous system. These pathological developments lead to impaired cognition, permanent memory loss in dementia and AD, and an inability of the brain to exert normal neuromuscular control, affecting motor functions and body movement in PD. A deeper understanding of the properties of HS in these degenerative processes is essential for the development of therapeutic measures to treat these conditions. Significant improvements in neuroimaging, next-generation glycosaminoglycan analytical techniques, and functional glycomics hold great promise for elucidating the complexities of HS structure and function. These advancements may significantly aid in the development of HS biotherapeutics to treat these debilitating conditions, which are increasingly impacting the aging global population. While a number of promising therapeutic candidates have already emerged, further research is required to optimize their biotherapeutic applications in this challenging area of pathobiology, bioregulation, and the recovery of neural function.

Exploring tau protein and amyloid-beta propagation: A sensitivity analysis of mathematical models based on biological data

Alzheimer’s disease is the most common dementia worldwide. Its pathological development is well known to be connected with the accumulation of two toxic proteins: tau protein and amyloid-β. Mathematical models and numerical simulations can predict the spreading patterns of misfolded proteins in this context. However, the calibration of the model parameters plays a crucial role in the final solution. In this work, we perform a sensitivity analysis of heterodimer and Fisher–Kolmogorov models to evaluate the impact of the equilibrium values of protein concentration on the solution patterns. We adopt advanced numerical methods such as the IMEX-DG method to accurately describe the propagating fronts in the propagation phenomena in a polygonal mesh of sagittal patient-specific brain geometry derived from magnetic resonance images. We calibrate the model parameters using biological measurements in the brain cortex for the tau protein and the amyloid-β in Alzheimer’s patients and controls. Finally, using the sensitivity analysis results, we discuss the applicability of both models in the correct simulation of the spreading of the two proteins.Statement of significance: Alzheimer’s disease is related to the accumulation of tau protein and amyloid-β. Mathematical models to predict the spreading patterns require accurate parameter calibration. In this work, we perform a sensitivity analysis of heterodimer and Fisher–Kolmogorov models to evaluate the impact of the equilibrium values of protein concentration on the solution patterns obtained with advanced numerical simulations on patient-specific brain geometry derived from magnetic resonance images. By using biological measurements in the brain cortex for the proteins in Alzheimer’s patients and controls, we use sensitivity analysis to discuss the applicability of models in simulating protein spreading.

Classic Dietiology or Holistic Nutritional Approach: What Type of Nutrition are We Working Towards?

In order to describe the negative aspects produced by the industrialized production of food that we present in this article, I have coined a definition that summarizes all the negative contents of the current diet: "PESTIFOOD", which is the portmanteau of the words PESTICIDE and FOOD. After a brief premise on the importance that healthy food has for the survival of living things, I critically describe the intensive production of food and the negative impact it has had on the emergence of numerous metabolic pathologies. So that due to the lack of nutritional value of the foods that industrial production provides us, we must record the growing development of new pathologies linked mainly to junk food and Pestifood. In the current state of degradation of food resources, not even the adoption of fortified foods or supplements can solve the root problem, represented by the use of chemical substances to improve production and extend the expiry date of foods. The only solution to the food problem for the future will be that of eco-sustainable choices, to recover the value of food as "our true medicine" - Hippocrates.

CLINICAL AND PARACLINICAL ASPECTS OF INTESTINAL FUNCTIONAL DISORDERS IN INFANTS

The aim of the work – to conduct an analysis of risk factors, clinical characteristics andresults of paraclinical examination of disorders of the functional state of the intestine ininfants who had a history of perinatal pathology.Materials and methods. A comprehensive clinical and paraclinical examination of 60infants during the period of catamnetic observation was carried out. The І group consistedof 36 children aged 6-7 months with disorders of the functional state of the gastrointestinaltract, the ІІ group – 25 healthy children of the same age category. The functional state ofthe intestines was assessed by determining the content of albumin, alpha-1-antitrypsin,elastase, PMN-elastase and fecal calprotectin levels in stools using the enzyme- linkedimmunosorbent assay (ELISA), reagents of the Immundiagnostic AG (Germany) companybased on German- Ukrainian laboratory «BUKINMED» (Chernivtsi, Ukraine).The results. Symptoms of disorders of the functional state of the intestines in infants are:restlessness and prolonged crying, poor sucking, loss of appetite, refusal to eat, vomiting,tendency to loose stools or constipation, flatulence and intestinal colic, body weightdeficiency. In the coprofiltrate of children of the I group, who had the signs of the functionalstate disorders of the intestine, compared with the control group, an increase in the contentof fecal calprotectin, alpha-1-antitrypsin, PMN-elastase and albumin was found, which areinterdependent criteria of the digestive system dysfunction. Laboratory indicators can actas markers of food intolerance and indicate the presence of local neutrophilic inflammation. Conclusions. Violations of the functional state of the intestines in infants havea multifactorial etiology caused by a combination of adverse effects of ante- and perinatalfactors on the fetal body, the development of perinatal pathology in newborns, as well asthe presence of diseases of the neonatal period.

The therapeutic potential of traditional Chinese medicine in depression: focused on the modulation of neuroplasticity.

Depression, a mood disorder characterized by a persistent low mood and lack of enjoyment, is considered the leading cause of non-fatal health losses worldwide. Neuroplasticity refers to the brain's ability to adapt to external or internal stimuli, resulting in functional and structural changes. This process plays a crucial role in the development of depression. Traditional Chinese Medicine (TCM) shows significant potential as a complementary and alternative therapy for neurological diseases, including depression. However, there has been no systematic summary of the role of neuroplasticity in the pathological development of depression and TCM Interventions currently. This review systematically summarized recent literature on changes in neuroplasticity in depression and analyzed the regulatory mechanisms of active metabolites in TCM and TCM formulas on neuroplasticity in antidepressant treatment. Additionally, this review discussed the limitations of current research and the application prospects of TCM in regulating neuroplasticity in antidepressant research.

Mailuoning oral liquid ameliorates vasculitis in thromboangiitis obliterans rats via inactivating cGAS-STING-IRF3 and TLR4-MAPKs/NF-κB signaling pathways

Ethnopharmacological relevanceMailuoning oral liquid (MLN O), one traditional Chinese patent medicine, has a good therapeutic effect on thromboangiitis obliterans (TAO) in clinical practice. However, the underlying mechanism remains unclear. Aim of the studyThis study aimed to explore the effects and potential mechanisms of MLN O against TAO based on network pharmacology and experimental verification. Materials and methodsNetwork pharmacology was used to identify the intersectional targets and signaling pathways of MLN O and TAO. In vivo, the TAO model was established by injecting sodium laurate and dihydrotestosterone (DHT) into the femoral arteries of Wistar rats. Rats were given the indicated drugs by intragastric administration (i.g.), intravenous injection (i.v.), or subcutaneous injection (s.c.) per day for 21 days since a week before surgery. In vitro, HUVECs, RAW264.7, and THP-1 cells were stimulated by LPS and DHT to simulate the pathological changes of TAO. The anti-inflammatory, anticoagulant, and immunomodulatory effects of MLN O were evaluated by histological observation, blood biochemical indexes detection, H&E staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), qRT-PCR, western blotting and immunofluorescence assays. Furthermore, the vascular ring test was applied to explore the vasodilatory activity of MLN O. ResultsMLN O significantly improved the pathological signs in TAO rats through its excellent anti-inflammatory, anticoagulant, immunomodulatory, and vasodilatory effects. Specifically, MLN O alleviated the gangrene and reduced the thrombosis in TAO rats, meanwhile, suppressed the expressions of inflammatory factors and clotting factors, which is related to the inactivations of cGAS-STING-IRF3 and TLR4-MAPKs/NF-κB signaling pathways. However, the superphysiological dose of DHT deteriorated the pathological development of TAO in vitro and in vivo. Moreover, the results of network pharmacology are consistent with the experimental verification. ConclusionCollectively, this study indicates for the first time that MLN O could alleviate TAO by inhibiting cGAS-STING-IRF3 and TLR4-MAPKs/NF-κB signaling pathways, which sheds light on a novel clinical therapeutic strategy for TAO.

METTL14-Mediated m6A Modification of TUG1 Represses Ferroptosis in Alzheimer's Disease via Inhibiting GDF15 Ubiquitination.

Alzheimer's disease (AD) is a neurodegenerative disease that remains a serious global health issue. Ferroptosis has been recognized as a vital driver of pathological progression of AD. However, the detailed regulatory mechanisms of ferroptosis during AD progression remain unclear. This study aimed to explore the regulatory role and mechanism of methyltransferase like 14 (METTL14) in ferroptosis in AD models. Serum samples were collected from 18 AD patients and 18 healthy volunteers to evaluate clinical correlation. Scopolamine-treated mice and Aβ1-42-stimulated SH-SY5Y cells were served as the in vivo and in vitro models of AD. Ferroptosis was detected by reactive oxygen species (ROS), Fe2+, total iron levels, and ferroptosis-related proteins glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). Cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. The N6-methyladenosine (m6A) modification was detected by RNA methylation quantification kit and methylated RNA immunoprecipitation sequencing-quantitative real-time polymerase chain reaction (MeRIP-qPCR). Molecular mechanisms were investigated by RNA pull-down, RNA immunoprecipitation (RIP), and co-immunoprecipitation (Co-IP) assays. Cognitive disorder of AD mice was measured by Morris water maze test. METTL14 was down-regulated, while lncRNA taurine upregulated gene 1 (TUG1) was up-regulated in clinical patients and experimental models of AD. Functional experiments demonstrated that METTL14 overexpression or TUG1 silencing effectively attenuated Aβ1-42-induced ferroptosis and neurotoxicity in SH-SY5Y cells. Mechanistically, METTL14-mediated m6A modification reduced the stability of TUG1. Moreover, TUG1 promoted the ubiquitination and degradation of growth differentiation factor 15 (GDF15) by directly interacted with Smad ubiquitin regulatory factor 1 (SMURF1), which consequently inactivated nuclear factor erythroid 2-related factor 2 (NRF2). Rescue experiments indicated that GDF15 depletion reversed sh-TUG1-mediated protection against ferroptosis and neurotoxicity. Finally, Mettl14 overexpression repressed ferroptosis to ameliorate the cognitive disorder via modulating Tug1/Gdf15/Nrf2 pathway in vivo. METTL14 inhibited ferroptosis to ameliorate AD pathological development by m6A modification of TUG1 to activate GDF15/NRF2 axis, providing a novel therapeutic target for AD.

ПРОГНОСТИЧЕСКИЙ АЛГОРИТМ ФОРМИРОВАНИЯ ЗАДЕРЖКИ ФИЗИЧЕСКОГО РАЗВИТИЯ У ДЕТЕЙ, ПЕРЕНЕСШИХ ВНУТРИУТРОБНУЮ НАРКОТИЧЕСКУЮ ИНТОКСИКАЦИЮ

Objective: to create prognostic tables for delayed physical development of children who have experienced drug intoxication in the prenatal period. Materials and methods. The research materials are presented by the study group (51 children) and the verification group of children (10 people). The study group consisted of children aged 1 to 14 years who had prenatal exposure to opiates. Research methods included medical history, follow-up observation and statistical processing of the data obtained using the “Statistica 9.0” program. Results. A prognostic algorithm has been created in tabular expression of the most informationally significant 19 risk factors that have both a prognostically significant and leveling effect on the formation of future delays in the child’s physical development. prognostic table of risk data for the development of delayed physical development in children born to drug-addicted women. The obtained data was verified by a verification group. The effectiveness was 90 % (9 prognostic scenarios adequately reflected upcoming events. Conclusion. The developed predictive algorithms for delayed physical development in children who were exposed to opiates in the prenatal period are applicable in the practice of a pediatrician and create a real opportunity to draw up individual scenarios. The data obtained will help to prevent the development of pathology in a timely manner.

New coronavirus infection COVID-19 as a predictor of the cardiovascular pathology development in health care workers

New coronavirus infection COVID-19 as a predictor of the cardiovascular pathology development in health care workers

Aquaporin-4 mis-localization slows glymphatic clearance of α-synuclein and promotes α-synuclein pathology and aggregate propagation.

The appearance of misfolded and aggregated proteins is a pathological hallmark of numerous neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. Sleep disruption is proposed to contribute to these pathological processes and is a common early feature among neurodegenerative disorders. Synucleinopathies are a subclass of neurodegenerative conditions defined by the presence of α-synuclein aggregates, which may not only enhance cell death, but also contribute to disease progression by seeding the formation of additional aggregates in neighboring cells. The mechanisms driving intercellular transmission of aggregates remains unclear. We propose that disruption of sleep-active glymphatic function, caused by loss of precise perivascular AQP4 localization, inhibits α-synuclein clearance and facilitates α-synuclein propagation and seeding. We examined human post-mortem frontal cortex and found that neocortical α-synuclein pathology was associated with AQP4 mis-localization throughout the gray matter. Using a transgenic mouse model lacking the adapter protein α-syntrophin, we observed that loss of perivascular AQP4 localization impairs the glymphatic clearance of α-synuclein from intersititial to cerebrospinal fluid. Using a mouse model of α-synuclein propogation, using pre-formed fibril injection, we observed that loss of perivascular AQP4 localization increased α-synuclein aggregates. Our results indicate α-synuclein clearance and propagation are mediated by glymphatic function and that AQP4 mis-localization observed in the presence of human synucleinopathy may contribute to the development and propagation of Lewy body pathology in conditions such as Lewy Body Dementia and Parkinson's disease.

Current trends in radiological diagnostics of the temporal bone pyramid pathologies

Diseases of the middle ear and the temporal bone pyramid remain one of the most common diseases in the structure of otorhinolaryngological pathologies, which have a significant impact on the quality of life of adults and children. Exudative processes, as well as their consequences, become one of the main causes of persistent hearing loss and are characterized by an asymptomatic course with a gradual evolution to chronic forms. It should be noted that in childhood the risk of impaired speech and intellectual development increases, leading to changes in the psycho-emotional status, social maladaptation of the child, and a decrease in the quality of life. Timely and complete diagnosis and high-quality follow-up takes a leading role in preventing the development of conductive hearing loss and other complicated pathologies of the temporal bone pyramid.<br /> Purpose of the study. To study the main predisposing factors, methods of radiological diagnosis and dynamic observation of patients, as well as some modern aspects of the treatment of the most common pathologies of the temporal bone pyramid.<br /> Methodology. We conducted an analytical review of open access sources from scientific databases such as Scopus, PubMed, Google Scholar, Web of Science, DisserCat, CyberLeninka. Key words used for the search: “chronic otitis media”, “cholesteatoma”, “mastoiditis”, “complications”, “magnetic resonance imaging”, “DWI”, “computed tomography”. Publications included in the literature review were full-text articles in English and Russian and dissertations in Russian. Exclusion criteria: brief reports, newspaper articles and personal communications. The search range was 5 years (2018-2023). A total of 108 sources were analyzed, of which 50 met the research objectives and inclusion criteria.<br /> Results and conclusions. In the diagnosis of temporal bone pathologies, the gold standard for diagnosis is computed tomography, but non-ionizing research techniques are increasingly used. Indications for the use of magnetic resonance imaging of the temporal bones are constantly expanding, and techniques for merging data with computed tomography data are being increasingly introduced. As a follow-up tool, magnetic resonance therapy is increasingly becoming a priority technique to reduce patient radiation exposure in the long term. In the treatment of complicated forms of diseases, endoscopic and laser correction techniques are used in foreign practice, helping to reduce the risk of recurrence and postoperative complications.<br /> <b>Key words</b>: chronic otitis media, cholesteatoma, magnetic resonance imaging, computed tomography, treatment