[Russian Medical Academy of Continuing Professional Education - the leading educational institution in the country for the training of forensic medical personnel (for the 90th anniversary from the establishment of the department of forensic medicine)]. / Rossiiskaya meditsinskaya akademiya nepreryvnogo professional'nogo obrazovaniya ­ vedushchee obrazovatel'noe uchrezhdenie strany po podgotovke sudebno-meditsinskikh kadrov (k 90-letiyu so dnya obrazovaniya kafedry sudebnoi meditsiny).

The article presents a detailed analysis of the stages of formation, development and achievements of the forensic medicine department of the Russian Medical Academy of Continuing Professional Education of the Ministry of Health of the Russian Federation, established in 1933 yr. More than 100 resident doctors and 15 PhD students have been trained in the department for 90 years. As a part of additional professional education implementation, more than 800 cycles of training courses for forensic medical and forensic experts and more than 30 cycles of professional retraining for doctors of other specialties have been carried out. More than 160 thous. specialists have been trained at the department since its establishment. Many employees of the department were directly involved in the performance of the most complicated and socially significant forensic medical examinations. The article describes the main achievements and scientific directions of the department's staff activity, directions and prospects of improving the training of forensic medical personnel in the country.

[Conceptual approaches to defining the one-pointedness of forensic expert institutions as a factor determining the effectiveness of their interaction]. / Kontseptual'nye podkhody k opredeleniyu odnoprofil'nosti sudebno-ekspertnykh uchrezhdenii kak faktor, opredelyayushchii effektivnost' ikh vzaimodeistviya.

THE OBJECTIVE OF THE STUDY: Is to identify the effectiveness of cooperation between forensic expert institutions on the basis of approaches to determining their one-pointedness. Legislative and regulatory legal acts regulating forensic expert activity have been studied. Methods of synthesis, analysis and comparison have been used for their processing. The comparison of the carrying out of targeted diversified studies has been conducted. The article substantiates a necessity of uniform approaches to determination of one-pointedness of forensic expert institutions in order to increase the effectiveness of interdepartmental interaction.

[Interdepartmental communication training for forensic medical experts]. / Trening mezhvedomstvennoi kommunikatsii vrachei ­ sudebno-meditsinskikh ekspertov.

THE OBJECTIVE OF THE STUDY: Is to identify the main communication problems encountered by forensic medical experts and specialists during the interdepartmental interaction, and to develop proposals to overcome them. A comprehensive approach was used to achieve the aim of the research, including the carrying out of a qualitative focus group interview of forensic medical experts and resident doctors. The main communicative problems have been determined and proposals for their elimination have been formulated, the types of communication trainings on interdepartmental interaction have been identified.

A phase II open-label trial of avelumab plus axitinib in previously treated non-small-cell lung cancer or treatment-naïve, cisplatin-ineligible urothelial cancer.

BACKGROUND: We hypothesized that avelumab plus axitinib could improve clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC) or urothelial carcinoma (UC). PATIENTS AND METHODS: We enrolled previously treated patients with advanced or metastatic NSCLC, or untreated, cisplatin-ineligible patients with advanced or metastatic UC. Patients received avelumab 800 mg every 2 weeks (Q2W) and axitinib 5 mg orally two times daily. The primary endpoint was objective response rate (ORR). Immunohistochemistry was used to assess programmed death-ligand 1 (PD-L1) expression (SP263 assay) and the presence of CD8+ T cells (clone C8/144B). Tumor mutational burden (TMB) was assessed by whole-exome sequencing. RESULTS: A total of 61 patients were enrolled and treated (NSCLC, n = 41; UC, n = 20); 5 remained on treatment at data cut-off (26 February 2021). The confirmed ORR was 31.7% in the NSCLC cohort and 10.0% in the UC cohort (all partial responses). Antitumor activity was observed irrespective of PD-L1 expression. In exploratory subgroups, ORRs were higher in patients with higher (≥median) CD8+ T cells in the tumor. ORRs were higher in patients with lower TMB (

[Influence of connective tissue differentiation on scar tissue formation in children]. / Vliyanie differentsiatsii soedinitel'noi tkani na formirovanie rubtsovoi tkani v detskom vozraste.

OBJECTIVE: To study the immunohistochemical features of various scar tissues in children without connective tissue pathology and with undifferentiated connective tissue dysplasia syndrome. MATERIAL AND METHODS: Tissue biopsy was performed in 217 children who underwent surgical treatment for various lesions, such as injuries, burns, as well as other procedures. There were 127 boys (58.5%) and 90 (41.5%) girls. The main group consisted of 98 (48.2%) children with scar tissue; group of UCTD syndrome - 65 (30.0%) children; control group - 43 (24.8%) patients without pathological scars. Histological examination of scar tissue and intact skin was carried out during primary or redo reconstructive surgery. Immunohistochemical study of antibodies against CD34, CD105, CD140b, PDGFs, COL types I, III and IV was performed. RESULTS: The study showed a quantitative characteristic of expression of COL type I in hypertrophic scar with predominance in the main group (77.5±5.4%; p<0.05), and decrease in COL type IV. Keloid form was associated with predominance of granulation tissue in all layers of dermis and high levels of all types of collagen. In the group of UCTD, COL type III prevailed in all pathological forms of the scar. We determined quantitative indicators of expression of vascularization factors (CD34; CD105) and fibroblastic activity (CD140b; PDGFs). CONCLUSION: Understanding the process of fibrinogenesis and analysis of stages of triggering mechanisms are essential for development of preventive algorithms. Individualized approach should be considered in the treatment. These studies are especially important in children with UCTD syndrome as high-risk group for pathological scarring. Thus, further research is required.

[Variants for conducting situational studies and expertises in forensic medical practice]. / Varianty provedeniya situatsionnykh issledovanii i ekspertiz v sudebno-meditsinskoi praktike.

The aim of the study is to analyze the features of commissioning and conducting the forensic situational studies and expertises and to consider variants for their practical implementation. The importance of a situational analysis when conducting various types of forensic medical expertises is considered. The variants for conducting situational studies and situational expertises in practical work are proposed.

[Methodological analysis of basic concepts and terms used in forensic medical ballistics and most frequently common mistakes]. / Metodologicheskii analiz osnovnykh poniatii i terminov, ispol'zuemykh v sudebno-meditsinskoi ballistike, i naibolee chasto vstrechaiushchiesia pri ikh primenenii oshibki.

The objective of this work was to determine the reasons and to find the ways to prevent common mistakes in using conceptual and terminology framework in forensic medical ballistics. Basic research and dissertation papers, practice guidelines and textbooks, educational learning materials, as well as conceptual and terminology frameworks of the regulatory legal acts of the Russian Federation had been analyzed. The study outcomes make it possible for a forensic medical expert to use basic definitions and terms of forensic medical ballistics in his/her practice methodologically correctly and in a well-argued manner, to reduce dramatically or completely exclude a possibility of expert's mistakes, to formulate reliable and sound conclusions upon the fact and conditions of a firearm use and upon a concrete mechanism of a gunshot wound formation in general.

[Overdose deaths from narcotic drugs and psychotropic substances in Russia (an analysis of materials for the period 2003 to 2018)]. / Smertel'nye otravleniia narkoticheskimi sredstvami i psikhotropnymi veshchestvami v Rossii (po materialam 2003-2018 gg.).

The purpose of the work is to study the prevalence of overdose deaths from narcotic drugs and psychotropic substances in Russia, as determined by forensic autopsies, for the period 2003 to 2018. For the study, medical statistics were processed, the percentages for each indication were calculated, and the changes in the percentages for different types of overdose deaths were noted. It was established in forensic autopsies for the period under study, that the percentage of narcotic overdose deaths ranged from 4.2% to 16.6% of the total number of poisonings, while the percentage of overdose deaths from psychotropic substances ranged from 0.7% to 1.3%.

[Forensic expertise as a tool for criminalistics prognostication]. / Sudebnaia ékspertiza kak instrument kriminalisticheskogo prognozirovaniia.

The objective of the present study was the criminalistics evaluation of the changes in the structure of the illegal drug market and the volume of drug sales that took place during the recent years. One of the most challenging problems associated with the new situation is the extensive distribution of synthetic cannabimimetics that constitutes one of the most serious threats to the public security. The criminological analysis of the forensic expert practice provided materials for the criminalistics characteristic of the recent events at the criminal drug market in several regions of this country as of 2014 with special reference to the cases of mass poisoning of the young people attributable to the use of the new psychoactive agents. The authors emphasize the important role of forensic medical and other forensic expertises for the identification and comprehensive evaluation of all the factors and circumstances associated with the current situation and characterizing the level of social unsafety under the conditions of the illegal trafficking of the new psychoactive substances. It is concluded that the further improvement of the criminal legislation is urgently needed to strengthen the responsibility for the participation in the subversive and terrorist activities.

[The program for the clinical residency and internship in the speciality 31.08.10 'forensic medical expertise' as a component of the integral educational space]. / Programma ordinatury po spetsial'nosti 31.08.10 Sudebno-meditsinskaia ékspertiza - sostavliaiushchaia edinogo obrazovatel'nogo prostranstva.

The objective of the present study was the development and implementation of the educational program for the training of the highly qualified specialists within the framework the clinical residency and internship in the speciality 31.08.10 'forensic medical expertise' aimed at the adherence to and the maintenance of the systemic approach to the training in compliance with the upgraded regulatory documents at the medical institutions of the Russian Federation authorized to carry out post-graduate educational activities. The residency program for the training of the highly qualified specialists in the speciality 31.08.10 'forensic medical expertise' has been developed and implemented based at the Russian Federal Centre of Forensic Medical Expertise with the extension of the elective part of the working residency program in order to provide the delivery of the lectures and holding seminars on the selected issues of forensic medicine and criminalistics. The ongoing modernization of the healthcare system in this country taking into consideration the public needs and the challenges for practical medicine, the necessity of formation of the integral educational medium, the development of the unique systemic approach to the effective training of the highly qualified specialists in forensic medical expertise, and further optimization of the educational process are intended to propel forensic medical education and the training of the forensic medical experts to the qualitatively new level.

Dynamics of a rolling robot.

Equations describing the rolling of a spherical ball on a horizontal surface are obtained, the motion being activated by an internal rotor driven by a battery mechanism. The rotor is modeled as a point mass mounted inside a spherical shell and caused to move in a prescribed circular orbit relative to the shell. The system is described in terms of four independent dimensionless parameters. The equations governing the angular momentum of the ball relative to the point of contact with the plane constitute a six-dimensional, nonholonomic, nonautonomous dynamical system with cubic nonlinearity. This system is decoupled from a subsidiary system that describes the trajectories of the center of the ball. Numerical integration of these equations for prescribed values of the parameters and initial conditions reveals a tendency toward chaotic behavior as the radius of the circular orbit of the point mass increases (other parameters being held constant). It is further shown that there is a range of values of the initial angular velocity of the shell for which chaotic trajectories are realized while contact between the shell and the plane is maintained. The predicted behavior has been observed in our experiments.

Expression quantitative trait loci (eQTLs) in microRNA genes are enriched for schizophrenia and bipolar disorder association signals.

BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) have substantial negative impact on the quality of human life. Both, microRNA (miRNA) expression profiling in SZ and BD postmortem brains [and genome-wide association studies (GWAS)] have implicated miRNAs in disease etiology. Here, we aim to determine whether significant GWAS signals observed in the Psychiatric Genetic Consortium (PGC) are enriched for miRNAs. METHOD: A two-stage approach was used to determine whether association signals from PGC affect miRNAs: (i) statistical assessment of enrichment using a Simes test and sum of squares test (SST) and (ii) biological evidence that quantitative trait loci (eQTL) mapping to known miRNA genes affect their expression in an independent sample of 78 postmortem brains from the Stanley Medical Research Institute. RESULTS: A total of 2567 independent single nucleotide polymorphisms (SNPs) (R2 > 0.8) were mapped locally, within 1 Mb, to all known miRNAs (miRBase v. 21). We show robust enrichment for SZ- and BD-related SNPs with miRNAs using Simes (SZ: p ≤ 0.0023, BD: p ≤ 0.038), which remained significant after adjusting for background inflation in SZ (empirical p = 0.018) and approached significance in BD (empirical p = 0.07). At a false discovery rate of 10%, we identified a total of 32 eQTLs to influence miRNA expression; 11 of these overlapped with BD. CONCLUSIONS: Our approach of integrating PGC findings with eQTL results can be used to generate specific hypotheses regarding the role of miRNAs in SZ and BD.

A meta-analysis of gene expression quantitative trait loci in brain.

Current catalogs of brain expression quantitative trait loci (eQTL) are incomplete and the findings do not replicate well across studies. All existing cortical eQTL studies are small and emphasize the need for a meta-analysis. We performed a meta-analysis of 424 brain samples across five studies to identify regulatory variants influencing gene expression in human cortex. We identified 3584 genes in autosomes and chromosome X with false discovery rate q<0.05 whose expression was significantly associated with DNA sequence variation. Consistent with previous eQTL studies, local regulatory variants tended to occur symmetrically around transcription start sites and the effect was more evident in studies with large sample sizes. In contrast to random SNPs, we observed that significant eQTLs were more likely to be near 5'-untranslated regions and intersect with regulatory features. Permutation-based enrichment analysis revealed that SNPs associated with schizophrenia and bipolar disorder were enriched among brain eQTLs. Genes with significant eQTL evidence were also strongly associated with diseases from OMIM (Online Mendelian Inheritance in Man) and the NHGRI (National Human Genome Research Institute) genome-wide association study catalog. Surprisingly, we found that a large proportion (28%) of ~1000 autosomal genes encoding proteins needed for mitochondrial structure or function were eQTLs (enrichment P-value=1.3 × 10(-9)), suggesting a potential role for common genetic variation influencing the robustness of energy supply in brain and a possible role in the etiology of some psychiatric disorders. These systematically generated eQTL information should be a valuable resource in determining the functional mechanisms of brain gene expression and the underlying biology of associations with psychiatric disorders.

Genome-wide pharmacogenomic analysis of response to treatment with antipsychotics.

Schizophrenia is an often devastating neuropsychiatric illness. Understanding the genetic variation affecting response to antipsychotics is important to develop novel diagnostic tests to match individual schizophrenia patients to the most effective and safe medication. In this study, we use a genome-wide approach to detect genetic variation underlying individual differences in response to treatment with the antipsychotics olanzapine, quetiapine, risperidone, ziprasidone and perphenazine. Our sample consisted of 738 subjects with DSM-IV schizophrenia who took part in the Clinical Antipsychotic Trials of Intervention Effectiveness. Subjects were genotyped using the Affymetrix 500 K genotyping platform plus a custom 164 K chip to improve genome-wide coverage. Treatment outcome was measured using the Positive and Negative Syndrome Scale. Our criterion for genome-wide significance was a prespecified threshold that ensures that, on an average, only 10% of the significant findings are false discoveries. The top statistical result reached significance at our prespecified threshold and involved a single-nucleotide polymorphism (SNP) in an intergenic region on chromosome 4p15. In addition, SNPs in Ankyrin Repeat and Sterile Alpha Motif Domain-Containing Protein 1B (ANKS1B) and in the Contactin-Associated Protein-Like 5 gene (CNTNAP5), which mediated the effects of olanzapine and risperidone on Negative symptoms, were very close to our threshold for declaring significance. The most significant SNP in CNTNAP5 is nonsynonymous, giving rise to an amino-acid substitution. In addition to highlighting our top results, we provide all P-values for download as a resource for investigators with the requisite samples to carry out replication. This study demonstrates the potential of genome-wide association studies to discover novel genes that mediate the effects of antipsychotics, which could eventually help to tailor drug treatment to schizophrenic patients.

[The distal pancreatic resection with spleen preservation: which collaterals can we rely on?].

The spleen preservation by distal pancreatic resection can be performed either with spleen vessels preservation or with the ligation of the least. The experiment evolved ligation of all gastric arteries but the short gastric arteries in 20 cadaveric organocomplexes, followed by ink perfusion through the left gastric and left gastro-epiploic arteries. The study was amplified with the intraoperative dopplerography of portal arteries of the spleen after crossclamping of the left gastro-epiploic and short gastric arteries. Ten patients after distal pancreatic resection with spleen preservation and splenic vessels ligation had the CT-angiography before and after the surgery. All the conducted studies demonstrated the incapability of short gastric arteries to supply the satisfactory spleen perfusion. The left gastro-epiploic artery proved to be the main source of splenic blood supply after splenic vessels ligation.

[On extended biopsy of the prostatic gland].

The aim of our trial was to investigate correlation between the size of the prostate and probability of cancer detection with transperineal biopsy. Transperineal 12-sample biopsy of the prostate was made in 203 men aged 48-58 years (mean age 68.0 +/- 8.6 years) suspected of having prostatic cancer (PC). Total detection of cancer was 33.5%. PC patients had higher levels of PSA, more frequent alterations at rectal palpation and transrectal ultrasound investigation, while mean size of the prostate was the same in cancer and cancer-free patients. Differences in PC detection rate in patients with different sizes of the prostate were statistically insignificant. Use of sextant biopsy could not detect PC in 15 males (22.1%) cases. Thus, there is no correlation between the size of the prostatic gland and diagnostic value of transperineal biopsy obtaining 12 tissue samples. The above data do not support the necessity of extended biopsy in patients with large prostate.

[Low-molecular DNA in blood plasma and spinal fluid of cancer patients].

Enhanced preoperative levels of low-molecular DNA in blood plasma and in cerebrospinal fluid were established in cancer patients. They rose even higher after surgery due to stress. Possible mechanisms are discussed.