[Problems of ethyl glucuronide use in ethanol consumption diagnosis]. / Problemy ispol'zovaniya etilglyukuronida v diagnostike upotrebleniya etanola.

Quantitative determination of ethyl glucuronide (EtG) in different biological objects in recent years has been positioned as one of the most reliable biomarkers of unconditional alcohol consumption. The aim of the study is to summarize the analytical methods of alcohol consumption testing with the use of EtG currently available in domestic and foreign literature and to present a schematic overview of possible errors in reproducibility and interpretation of research on EtG results, which may limit their use in forensic medical practice. The main objective is to increase the reliability and validity of EtG as a marker of ethanol consumption.

[The role of antidiabetic drugs in the treatment of Alzheimer's disease: systematic review].

Recent studies show that Alzheimer's disease (AD) has many common links with conditions associated with insulin resistance, including neuroinflammation, impaired insulin signaling, oxidative stress, mitochondrial dysfunction and metabolic syndrome. The authors conducted an electronic search for publications in the PubMed/MEDLINE and Google Scholar databases using the keywords "amyloid beta", "Alzheimer type-3-diabetes", "intranasal insulin", "metformin", "type 2 diabetes mellitus", "incretins" and "PPARy agonists¼. A systematic literature search was conducted among studies published between 2005 and 2022. The authors used the following inclusion criteria: 1) Subjects who received therapy for AD and/or DM2, if the expected result concerned the risk of cognitive decline or the development of dementia; 2) The age of the study participants is > 50 years; 3) The type of studies included in this review were randomized clinical trials, population-based observational studies or case-control studies, prospective cohort studies, as well as reviews and meta-analyses; 4) The included articles were written in English. In recent years, there has been considerable interest in identifying the mechanisms of action of antidiabetic drugs and their potential use in AD. Human studies involving patients with mild cognitive impairment and Alzheimer's disease have shown that the administration of certain antidiabetic drugs, such as intranasal insulin, metformin, incretins and thiazolidinediones, can improve cognitive function and memory. The purpose of this study is to evaluate the effectiveness of antidiabetic drugs in the treatment of AD. According to the results of the study, metformin, intranasal insulin, thiazolidinediones and incretins showed a positive effect both in humans and in animal models. Recent studies show that thiazolidinediones can activate pathways in the brain that are regulated by IGF-1; however, rosiglitazone may pose a significant risk of side effects. The results of clinical studies on the use of metformin in AD are limited and contradictory.

[Determination of the corpse's stay in the water duration according to maceration degree of its skin]. / Opredelenie dlitel'nosti prebyvaniya trupa v vode po stepeni vyrazhennosti matseratsii ego kozhnogo pokrova.

A serious problem during the postmortem examination of a corpse extracted from the water can be a significant determination of its stay in the water duration. First of all, the signs indicating the presence of a corpse in the water include maceration, according to the severity of which forensic experts often determine how long the corpse stayed in the water. The aim of the study is to summarize the available literature data and propose ways to objectify the determination of a corpse's stay in water duration by the severity of skin maceration. In this article, based on the analysis of literature, the process of skin maceration is described, as well as the timing and speed of its development according to various authors. The presence of quite a large number of external and internal factors affecting the process of skin maceration and the subjectivity of its severity assessment is indicated. This article provides examples of the biophysical methods usage for the study of biological objects in forensic medical examination, allowing to objectively record changes in the researcher's parameter of interest. The use of skin impedancemetry to objectify the severity of skin maceration.

[Metformin and malignant neoplasms: a possible mechanism of antitumor action and prospects for use in practice].

Metformin is a first-line antidiabetic drug for the treatment of type 2 diabetes mellitus (DM2); its molecular target is AMP-activated protein kinase (AMPK), which is involved in many metabolic processes. Metformin not only reduces blood glucose levels and improves insulin sensitivity, but also inhibits lipolysis and reduces cardiovascular risk in patients with DM2. In recent years, it has been proven that metformin slows down the aging process, stimulates hair growth, eliminates cognitive impairment, and also has an antitumor effect. Most basic studies have shown that metformin inhibits the growth of tumor cells and promotes cellular apoptosis, while clinical studies show contradictory results. This discrepancy can be explained by the difference in the concentration of metformin between basic and clinical studies. The maximum daily dose of metformin for patients with DM2 is 2500 mg / day, and the dose used in basic research was much higher. Metformin directly activates the AMPK signaling pathway, inhibits the production of reactive oxygen species, induces the activation of mTORC1, inhibits cyclin D1, which leads to a reduction in the risk of the occurrence and development of malignant neoplasms. In addition, metformin indirectly inhibits tumor growth, proliferation, invasion and metastasis by reducing the concentration of glucose in the blood, insulin resistance, as well as by reducing inflammation and affecting the tumor microenvironment. Glycolysis plays an important role in the energy metabolism of tumors, and metformin is able to have an inhibitory effect on it. Currently, studies of the mechanism of antitumor effects of metformin are becoming more extensive and in-depth, but there are still some contradictions.

[Diabetic gastroenteropathy: modern methods of diagnosis and treatment].

Diabetes mellitus is a chronic disease with a growing prevalence worldwide, however, the prevalence of its complications, including gastroenteropathy, is also increasing. The pathophysiology of diabetic gastroenteropathy (DH) combines hyperglycemia, vagus nerve dysfunction, decreased expression of nitric oxide synthase in the myenteric plexus, changes in the interstitial Cajal cell network, as well as oxidative stress. Clinical signs of DH are gastroesophageal reflux, gastroparesis, constipation, abdominal pain and diarrhea. Among the diagnostic methods are manometry with pH measurement (assessment of esophageal motility), gastric emptying scintigraphy, respiratory test (to assess gastroparesis), aspiration and cultivation of the contents of the jejunum (to diagnose bacterial overgrowth syndrome). To date, there is no definitive treatment for DH - an interdisciplinary approach is aimed at slowing the progression of the disease, relieving symptoms and restoring gastrointestinal function. Patients are recommended a diet low in simple sugars and high in fiber; optimization of glycemic control with a target glycemia of less than 180 mg/dl. As for drug therapy, the use of prokinetics and antiemetics is justified, and in case of excessive bacterial growth syndrome, antibacterial therapy (rifaximin) is carried out. Modern approaches to the treatment of DH are also accumulating, including the use of botulinum toxin, pyloroplasty and electrical stimulation of the stomach in individual patients. Despite the constant development of new treatments, they are not yet able to completely cure DH in the near future, which makes it necessary to conduct further research in this area.

[Testosterone and Alzheimer's disease].

Alzheimer's disease (AD) is a neurodegenerative disease that causes dementia in half of the cases. Asthma is usually found in people over 65 years of age. The etiopathogenesis of the disease is multifactorial and includes genetic factors, nutritional disorders, mitochondrial dysfunction, oxidative stress, and aging. Sex hormones have an important influence on the development of AD, as evidenced by a higher incidence in women than in men. Considering the significant influence of T on the maintenance of normal brain function, the present study is aimed at evaluating the impact of androgen deprivation therapy (ADT), as well as testosterone therapy, on the risk of AD development and progression. Although there is some clinical inconsistency between studies, androgens have a significant effect on brain function and are beneficial for AD patients. Low levels of circulating androgens should be considered as a significant risk factor for the development of AD and memory loss. With a reduced level of T in the plasma of men, its administration improves cognitive performance and memory, treatment should be started at an early stage of the disease. In men and women with AD, androgens improve mental state and slow the progression of the disease, providing a protective effect. In the future, it is necessary to conduct studies on a large population, taking into account personality factors and a more specific approach to assessing cognitive functions and the causal relationship of T administration in AD.

[Current view on stab/cut injuries]. / Sovremennoe sostoyanie voprosa koloto-rezanykh povrezhdenii.

Currently, mechanical trauma is the most significant cause of violent death. The injuries caused by sharp objects rank high in the structure of mechanical trauma. The study objective is to review domestic and foreign literature on the study of stab/cut injuries, identify the main issues and consider new promising diagnostic methods. The stab/cut wound morphology is widely described in the available literature, but little attention has been paid to their study of late postmortem changes. This issue requires consideration since putrefactive corpses (hidden by placing the corpse in water, burying it in the ground, etc.) are often the object of forensic medical examination. New methods for assessing stab/cut injuries are also considered: computed tomography, multilayer computed tomography, scanning electron microscopy, and energy dispersive x-ray spectroscopy. Each of the diagnostic methods has its undeniable advantages and prospects for widespread use in expert practice, but they cannot completely replace the main methods and are intended only to supplement them.

[Analytical and synthesizing part of the forensic expert panel conclusion: a case study of professional violation of healthcare professionals]. / Analitiko-sinteziruyushchaya chast' zaklyucheniya sudebno-meditsinskoi ekspertnoi komissii na primere del o professional'nykh pravonarusheniyakh meditsinskikh rabotnikov.

The objective of the study is to develop scientific criteria for the analytical and synthesizing part of the expert report on 'medical cases.' We studied 15 conclusions of expert panels. The following research methods were used: logical and analytical, logical and synthetic (generalization), comparative, systemic and analytical (analysis of relations between facts). For the first time, a new algorithm for the analytical and synthesizing part of the expert report was proposed; and also ways to improve the quality of forensic reports for all types of expert examinations, including those involving non-state forensic experts, were described. These improvements make the results of expert examinations and reviews more convenient and objective. They are intended for non-state forensic experts, attorneys who use them, and state forensic experts, including during the training and professional development.

[Imeglimin: features of the mechanism of action and potential benefits].

Imeglimin is the first drug in a new class of tetrahydrotriazine-containing oral hypoglycemic agents called «glimines¼. Its mechanism of action is aimed at achieving a double effect, firstly, to improve the function of beta cells of the pancreas, and secondly, to enhance the action of insulin in key tissues, including the liver and skeletal muscles. At the cellular level, imeglimin modulates mitochondrial function, which leads to an improvement in cellular energy metabolism, as well as to the protection of cells from death in conditions of excessive accumulation of reactive oxygen species. It is important to note that the mechanism of action of imeglimin differs from existing drugs used for the treatment of type 2 diabetes mellitus. Like glucagon-like peptide-1 receptor agonists, imeglimin enhances insulin secretion in an exclusively glucose-dependent manner, but their mechanism of action at the cellular level diverges. Sulfonylureas and glinides function by closing ATP-sensitive potassium channels to release insulin, which is also different from imeglimin. Compared with metformin, the effect of imeglimine is also significantly different. Other major classes of oral antihypertensive agents, such as sodium-glucose transporter-2 inhibitors, thiazolidinediones and α glucosidase inhibitors mediate their action through mechanisms that do not overlap with imeglimine. Given such differences in the mechanisms of action, imeglimin can be used as part of combination therapy, for example with sitagliptin and metformin. The imeglimine molecule is well absorbed (Tmax-4), and the half-life is 5-6 hours, is largely excreted through the kidneys, and also has no clinically significant interactions with either metformin or sitagliptin.

[Estimation of time since death with the postmortem microbiome: a modern view and approaches to solving the problem]. / Opredelenie davnosti nastupleniya smerti s pomoshch'yu posmertnogo mikrobioma: sovremennyi vzglyad i podkhody k resheniyu problemy.

The aim of the review is to summarize and update the data of modern studies devoted to determining the post-mortem interval (PMI) with the use of microorganisms, as well as disclosing prospects for further study in the presented direction. Estimating the time elapsed since death based on the postmortem microbiome has great potential for accurate determination of PMI, but all methods currently used have their limitations. The dynamics of changes in microbial communities due to the influence of many external and internal factors significantly complicates the process of interpreting the results. The change of microbial communities in the human corpse has shown promising results for the assessment of PMI, but to date there is no evidence of the repeatability of such a continuity in various geographic and ecological conditions. The question of conducting new, large-scale studies, taking in all the factors that could affect the posthumous microbiome, is becoming urgent.

[Diagnostics of the presence of once of death and peculiarities of performance of the forensic medical examination in post-mortal facial condition]. / Diagnostika davnosti nastupleniya smerti i osobennosti provedeniya sudebno-meditsinskoi ekspertizy pri posmertnom oledenenii trupa.

The purpose of the research is to summarize the current information about post-mortem interval (PMI) estimating and the peculiarities of the forensic medical examination in postmortem glaciation of the corpse. On the territory of most regions of the Russian Federation, the autumn-winter period passes with a significant decrease in ambient temperature, which makes this topic relevant. The article describes in detail the mechanisms of freezing of human cells and tissues, methods for diagnosing PMI, the peculiarities of the examination in postmortem glaciation, and also put forward directions for further research.

[Current views on methods of determining the age of injuries in the practice of the forensic expert]. / Sovremennyi vzglyad na metody opredeleniya davnosti povrezhdenii v praktike sudebno-meditsinskogo eksperta.

The review objective is to summarize the current data on new methods development for detection and determination of the age of injuries (AI) and to analyze the prospects of their use in the practice of forensic medical experts. The injury healing processes in various human body tissues are described in detail, and data on biomarkers of healing and their role are provided. Three main diagnostic methods for AI were analyzed: immunohistochemical, molecular biological study, and biophysical objectivization. Their advantages and disadvantages, as well as ways of further improvement of these methods, are considered.

[Androgens and Parkinson's disease: the role in humans and in experiment].

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. There is evidence that PD has a wider prevalence among men, which indicates the existing role of sex hormones in the pathogenesis of the disease. The article presents an overview of studies devoted to the study of sex differences in the incidence and symptoms of PD. Drug therapy with androgens, androgen precursors, antiandrogens and drugs that modify androgen metabolism is available for the treatment of various endocrine conditions, having translational significance for PD, but none of these drugs has yet shown sufficient effectiveness. Although PD has now been proven to be more common in men than in women, androgens do not always have any effect on the symptoms or progression of the disease. 5α-reductase inhibitors have shown neuroprotective and anti-dyskinetic activity and need further investigation. Despite the fact that the neuroprotective effect of dutasteride was observed only before damage to DA neurons, the absence of a negative effect makes it an attractive drug for use in patients with PD due to its anti-dyskinetic properties.

[Personality factors' influence (gender, age, death category) on indicators of biophysical objectification of intra-vital injuries of a putrefactive corpse]. / Vliyanie faktorov individual'nosti (pol, vozrast, kategoriya smerti) na pokazateli biofizicheskoi ob"ektivizatsii prizhiznennykh povrezhdenii gnilostno izmenennogo trupa.

OBJECTIVE: Determination of the personality factors influence (gender, age, death category) on the numerical indicators of electrical characteristics during biophysical objectification of soft tissue injuries in a putrefactive corpse. The study was carried out based on Bureau of Forensic Medicine of the Bashkortostan Republic. The instrumental method examined 177 putrefactive corpses; 78 are female and 99 are male. Measurement of electrical characteristics (electrical capacity, electrical resistance) was carried out by an invasive method using a submersible sensor. It was established a significant effect of a person's age, gender and death category on the results of instrumental measurements. These individual characteristics can be recognized as factors that determine the electrical resistance and electrical capacity of biological tissues.

[Forensic aspects of sudden autopsy-negative cardiac death]. / Sudebno-meditsinskie aspekty vnezapnoi autopsiya-otritsatel'noi serdechnoi smerti.

The review of the world literature on the most common causes, mechanism of development and diagnostic signs of sudden autopsy-negative cardiac death is presented. Two groups of reasons for the development of this pathology were identified - traumatic and non-traumatic. The traumatic group includes the cardio-inhibitory reflex and the trigemino-cardiac reflex. The non-traumatic group included prolonged Q-T interval syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia. The importance of postmortem molecular genetic research in cases of sudden cardiac death in order to prevent the deaths in the victim's relatives is noted. The criteria for the diagnosis of reflex cardiac arrest are indicated.

[Significance of computerized, magnetic resonance and ultrasound tomography in the diagnosis of spreading of pulmonary cancer to the mediastinum]. / Znachenie komp'iuternoi, magnitnoi rezonansnoi i ul'trazvukovoi tomografii v oprededelenii rasprosteranennosti raka legkogo na sredostenie.

In 232 patients predominantly with the central type of lung cancer underwent echotomography (ET) (n = 16), CT (n = 142) and MRT (n = 55) in order to evaluate their possibilities in the diagnosis of the spread of a tumor process to the mediastinum and their impact on disease staging. The results of the techniques and the data of surgical interventions were compared: CT in 55 patients, CT in 70 and MRT in 22. The sensitivity of each method was determined by 3 parameters: 1) detection of intrathoracic lymphadenopathy; 2) diseased mediastinal large vessels; and 3) cancer spread to the pleura, pericardium, heart, and chest. Routine tomography is of informative value in the diagnosis of metastases into a peritracheo-bronchial group of lymph nodes (its sensitivity, 66%), ET, for paravasal (91%), CT and MRT for any groups of mediastinal lymph nodes (89-100%). MRT and ET (with sensitivities of 80 and 100%, respectively) were the methods of choice in the assessment of vascular lesions. MRT and CT are the most potent in evaluating the pleura, pericardium, and chest. The application of new techniques allows the clinical disease stage to be changed in 520 patients. Only X-ray and bronchological studies of patients with suspected lung cancer are not sufficient. ET either CT or MPR should be supplemented.

[Potentialities of ultrasound and computed tomography in the diagnosis of metastases of lung cancer in the mediastinal lymph nodes]. / Vozmozhnosti ul'trazvukovoi i komp'iuternoi tomografii v diagnostike metastazov raka legkogo v mediastinal'nye limfaticheskie uzly.

The results of routine roentgenotomography, CT and USI in the diagnosis of intrathoracic metastases of lung cancer were compared in 69 patients (central type--52, peripheral--17). These results were compared with operative findings in 45 patients. The sensitivity of USI in the diagnosis of enlarged paravasal lymph nodes exceeded that of roentgenotomography and was slightly inferior to CT. CT was informative for all mediastinal lymph nodes whereas tomography and USI were informative in certain areas only. The authors recommend to combine the use of routine and ultrasound tomography to assess the spreading of lung cancer to the mediastinum. The information obtained increases the accuracy of staging and specifying a process, slightly yielding CT results.

[Ultrasonic tomography of the mediastinum in the staging of lung cancer]. / Ul'trazvukovaia tomografiia sredosteniia v stadirovanii raka legkogo.

Results of standard X-ray tomography, computed tomography and ultrasonic tomography (UT) used for detecting mediastinal metastases from lung cancer were compared in 50 patients who were later operated on. UT sensitivity in the diagnosis of paravasal lymph node involvement proved superior to that of X-ray tomography and only slightly yielded to that of computed tomography. As regards bifurcation lymph node assessment, results of the radiation imaging techniques were similar to those obtained by surgery. Ultrasonographic signs of tumor spreading to the mediastinum were observed in cases of stage IIIa-IIIb tumors only. UT assured detection of metastases in normal-sized lymph nodes of the upper mediastinum. Combined application of standard X-ray and ultrasonic tomography of the mediastinum assured better staging of tumor roughly in half the patients. Absence of X-ray signs of mediastinal lymph node enlargement is considered a direct indication for UT.