Novel missense variants in brain morphogenic genes associated with depression and schizophrenia.

Introduction: Impaired function of brain morphogenic genes is considered one of the predisposing factors for the manifestation of psychiatric and cognitive disorders, such as paranoid schizophrenia (SCZ) and major depressive disorder (MDD). Identification of such genes (genes of neurotrophic factors and guidance molecules among them) and their deleterious genetic variants serves as a key to diagnosis, prevention, and possibly treatment of such disorders. In this study, we have examined the prevalence of genomic variants in brain morphogenic genes in individuals with SCZ and MDD within a Russian population.

Cell-Free Tumor DNA Detection-Based Liquid Biopsy of Plasma and Bile in Patients with Various Pancreatic Neoplasms.

The key challenge of cell-free tumor DNA (cftDNA) analysis in pancreatic ductal adenocarcinoma (PDAC) is overcoming its low detection rate, which is mainly explained by the overall scarcity of this biomarker in plasma. Obstructive jaundice is a frequent event in PDAC, which enables bile collection as a part of routine treatment. The aim of this study was to evaluate the performance of -mutated cftDNA detection-based liquid biopsy of plasma and bile in patients with pancreatic neoplasms using digital droplet PCR.

[Androgenic status of men with severe COVID-19: the role of testosterone and dihydrotestosterone [within the program FOUNDER (features of a new coronavirus infection course and options therapy depending on the androgenic status)]].

Purpose: The aim of this study was to assess the mens androgen status influence on the severity and outcomes (transfer of patients to the ICU or death) of COVID-19 required hospital hospitalization.

Materials And Methods: The study included 151 hospitalized men with a confirmed diagnosis of COVID-19. To measure the severity of disease have been used Symptomatic Hospital and Outpatient Clinical Scale for COVID-19 (SHOCS-COVID).

Microbiological and Cytokine Profiling of Menstrual Blood for the Assessment of Endometrial Receptivity: A Pilot Study.

Endometrial receptivity (ER) is a key factor required for the successful implantation of the embryo. However, the evaluation of ER is challenging, as a nondisruptive sampling of endometrial biomaterial by conventional methods is only possible outside of the embryo transfer (ET) cycle. We propose a novel approach for the assessment of ER-microbiological and cytokine profiling of menstrual blood aspirated directly from the uterine cavity at the beginning of the cryo-ET cycle.

Comparison of microbial profiles and viral status along the vagina-cervix-endometrium continuum of infertile patients.

For decades, the endometrium was considered to be a sterile environment. However, now this concept is disputed, and there is growing evidence that microbiota composition might affect endometrial receptivity. Routine clinical management of infertility is still limited to a microbiological assessment of the lower reproductive tract.

Correlations between biomarkers of senescent cell accumulation at the systemic, tissue and cellular levels in elderly patients.

The aim of the study was to investigate the relationship between established clinical systemic biomarkers of ageing and the development of age-associated diseases and senescent cell biomarkers at tissue and cellular levels. Thirty-eight patients (mean age 70 ± 4.9 years) who were assessed for traditional risk factors for cardiovascular diseases were included.

Development of a Sensitive Digital Droplet PCR Screening Assay for the Detection of Non-Coding Mutations in Bladder Cancer Urine Liquid Biopsies.

Recent whole-genome sequencing studies identified two novel recurrent mutations in the enhancer region of in urothelial bladder cancer (UBC) tumor samples. This mutational hotspot is the second most common after the promoter in UBC. The aim of the study was to develop a digital droplet PCR screening assay for the simultaneous detection of mutations in a single tube.

Proactive anti-inflammatory therapy in the advanced stages of a new coronavirus infection. Main results of the inpatient phase of the COLORIT study (Colchicin vs. Ruxolitinib and secukinumab in an open, prospective, randomized trial in patients with novel coronavirus infection COVID-19).

Aim      To evaluate clinical efficacy of the proactive anti-inflammatory therapy in patients hospitalized for COVID-19 with pneumonia and a risk of "cytokine storm".Material and methods  The COLORIT study was a comparative study with randomization into 4 groups: colchicine (n=21) 1 mg for the first 3 days followed by 0.5 mg/day through day 12 or discharge from the hospital; secukinumab 300 mg/day, s.

[Risk of postoperative complications in hyperglycemic conditions].

The authors consider the influence of carbohydrate metabolism disorders on postoperative period. Data on the influence of diabetes mellitus on morbidity are summarized. Mechanisms and significance of stress-induced hyperglycemia are described.

The Association of Genotype and Soluble suPAR Serum Level with COVID-19-Related Lung Damage Severity.

Uncovering the risk factors for acute respiratory disease coronavirus 2019 (COVID-19) severity may help to provide a valuable tool for early patient stratification and proper treatment implementation, improving the patient outcome and lowering the burden on the healthcare system. Here we report the results of a single-center retrospective cohort study on 151 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected symptomatic hospitalized adult patients. We assessed the association of several blood test measurements, soluble urokinase receptor (uPAR) serum level and specific single nucleotide polymorphisms of (I/D), (rs2070744, rs1799983), (rs1799768), (rs2227564) and (rs344781, rs2302524) genes, with the disease severity classified by the percentage of lung involvement on computerized tomography scans.

[Correlations between vessel stiffness and biomarkers of senescent cell in elderly patients].

Aim    To study the association between vascular wall stiffness and known markers for accumulation of senescent cells in blood, cells, and tissues of old patients.Material and methods    This study included male and female patients aged 65 years and older who were referred to an elective surgical intervention, that included a surgical incision in the area of the anterior abdominal wall or large joints and met the inclusion and exclusion criteria. For all patients, traditional cardiovascular (CV) risk factors and arterial wall stiffness (pulse wave velocity, PWV) were evaluated.

[Features of a new corOnavirUs infection course and optioNs therapy DEpending on the andRogenic status (FOUNDER): androgenic status in men with COVID-19 and its relationship with the disease severity].

Objective: Analysis of androgen status in men hospitalized with a moderate COVID-19 and its relationship with the severity of the disease.

Materials And Methods: The study included 152 males with a confirmed diagnosis of COVID-19 based on the results of a positive PCR for the SARS-CoV-2 virus and/or computed tomography of the lungs hospitalized at the MSU University Clinic due to the moderate and severe COVID-19. Examination of the level of biochemical blood parameters (CRP, creatinine, urea, glucose, total testosterone (T)); CT of the lungs.

Urine TERT promoter mutations-based tumor DNA detection in patients with bladder cancer: A pilot study.

Telomerase reverse transcriptase (TERT) promoter mutations are the most frequent genetic events in bladder cancer (BC). The aim of the present pilot study was to evaluate the diagnostic potential of urine TERT promoter mutations-based liquid biopsy in patients with an ongoing oncological process, as well as in post-resection patients at risk of BC recurrence. A total of 60 patients were enrolled, of whom 27 patients had histologically proven BC; 23 had no signs of BC (control group); and 10 patients underwent transurethral malignancy resection 3-6 months prior to urine donation ('second look' group).

T-Cadherin and the Ratio of Its Ligands as Predictors of Carotid Atherosclerosis: A Pilot Study.

In the cardiovascular system, atherogenic low-density lipoproteins (LDL) and the protective hormone adiponectin bind to the same receptor, T-cadherin. In this study, we tested the hypothesis that the ratio of circulating LDL to high-molecular weight (HMW) adiponectin could predict the development of atherosclerosis. Using enzyme-linked immunosorbent assay, we measured the level of circulating HMW adiponectin in the blood of donors together with ultrasound measuring of intima-media thickness (IMT) of carotid arteries.

Mucosal biomarkers for endometrial receptivity: A promising yet underexplored aspect of reproductive medicine.

Annually, approximately 2 million assisted reproductive technology (ART) procedures are performed worldwide, of which, only ~25% lead to successful delivery. There are two major factors contributing to successful implantation: embryo quality and endometrial receptivity (ER). Although embryo quality might be assessed through morphological and genetic testing, no clinically approved techniques are available to evaluate ER.

Phenotyping Angiotensin-Converting Enzyme in Blood: A Necessary Approach for Precision Medicine.

Background: Angiotensin-converting enzyme (ACE) metabolizes a number of important peptides participating in blood pressure regulation and vascular remodeling. Elevated ACE expression in tissues (which is generally reflected by ACE in blood) is associated with increased risk of cardiovascular diseases. Elevated ACE in blood is also a marker for granulomatous diseases.

[Association of AGT, ACE, NOS3, TNF, MMP9, CYBA polymorphism with subclinical arterial wall changes].

Aim    Activation of the renin-angiotensin-aldosterone system, decreased nitric oxide production, chronic inflammation, and oxidative stress result in subclinical changes in the arterial wall, which favor the development of cardiovascular diseases (CVD). The effect of allelic gene variants that encode the proteins participating in pathogenetic pathways of age-associated diseases with subclinical changes in the arterial wall [increased pulse wave velocity (PWV), increased intima-media thickness, endothelial dysfunction (ED), presence of atherosclerotic plaques (ASP)] are understudied. This study analyzed the relationship between AGT, ACE, NOS3 TNF, MMP9, and CYBA gene polymorphism and the presence of subclinical changes in the arterial wall, including the dependence on risk factors for CVD, in arbitrarily healthy people of various age.

Proactive anti-inflammatory therapy with colchicine in the treatment of advanced stages of new coronavirus infection. The first results of the COLORIT study.

Actuality The course of the novel coronavirus disease (COVID-19) is unpredictable. It manifests in some cases as increasing inflammation to even the onset of a cytokine storm and irreversible progression of acute respiratory syndrome, which is associated with the risk of death in patients. Thus, proactive anti-inflammatory therapy remains an open serious question in patients with COVID-19 and pneumonia, who still have signs of inflammation on days 7-9 of the disease: elevated C-reactive protein (CRP)>60 mg/dL and at least two of the four clinical signs: fever >37.

Results of Open-Label non-Randomized Comparative Clinical Trial: "BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT).

Introduction The aim of this study was to assess the efficacy and safety of a combination of bromhexine at a dose of 8 mg 4 times a day and spironolactone 50 mg per day in patients with mild and moderate COVID 19.Material and methods It was an open, prospective comparative non-randomized study. 103 patients were included (33 in the bromhexine and spironolactone group and 70 in the control group).

[Phenotyping of angiotensin-converting enzyme in the prostate in patients with prostate cancer and benign prostatic hyperplasia].

Background: Angiotensin-converting enzyme (ACE) is expressed by all epithelial cells of the human body. Although the main proportion of ACE is synthesized by the lungs, in men, ACE is also secreted by the testes (testicular form), seminal vesicles and the prostate. In semen, the level of ACE is up to 50 times higher than in blood plasma.

[Combination therapy at an early stage of the novel coronavirus infection (COVID-19). Case series and design of the clinical trial "BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)"].

The article focuses on effective treatment of the novel coronavirus infection (COVID-19) at early stages and substantiates the requirement for antiviral therapy and for decreasing the viral load to prevent the infection progression. The absence of a specific antiviral therapy for the SARS-CoV-2 virus is stated. The authors analyzed results of early randomized studies using lopinavir/ritonavir, remdesivir, and favipiravir in COVID-19 and their potential for the treatment of novel coronavirus infection.

[Proactive anti-inflammatory and anticoagulant therapy in the treatment of advanced stages of novel coronavirus infection (COVID-19). Case Series and Study Design: COLchicine versus ruxolitinib and secukinumab in open prospective randomIzed trial (COLORIT)].

The article is devoted to the treatment of the new coronavirus infection (COVID-19) in the advanced stages of the disease. The types of response of the immune system to the viral load of SARS-CoV-2 with the start of the inflammation process are considered. The situation is analyzed in detail in which the growing autoimmune inflammation (up to the development of a "cytokine storm") affects not only the pulmonary parenchyma, but also the endothelium of the small vessels of the lungs.

Novel ACE mutations mimicking sarcoidosis by increasing blood ACE levels.

An elevated blood angiotensin I-converting enzyme (ACE) supports diagnosis of sarcoidosis and Gaucher disease. However, some ACE mutations increase ACE shedding, and patients with these mutations are therefore at risk of being incorrectly diagnosed with sarcoidosis because of elevated serum ACE levels. We applied a novel approach called "ACE phenotyping" to identify possible ACE mutations in 3 pulmonary clinic patients that had suspected sarcoidosis based on elevated blood ACE levels.

Steroid pulse -therapy in patients With coronAvirus Pneumonia (COVID-19), sYstemic inFlammation And Risk of vEnous thRombosis and thromboembolism (WAYFARER Study).

Introduction Coronavirus pneumonia not only severely affects the lung tissue but is also associated with systemic autoimmune inflammation, rapid overactivation of cytokines and chemokines known as "cytokine storm", and a high risk of thrombosis and thromboembolism. Since there is no specific therapy for this new coronavirus infection (COVID-19), searching for an effective and safe anti-inflammatory therapy is critical.Materials and methods This study evaluated efficacy and safety of pulse therapy with high doses of glucocorticosteroids (GCS), methylprednisolone 1,000 mg for 3 days plus dexamethasone 8 mg for another 3-5 days, in 17 patients with severe coronavirus pneumonia as a part of retrospective comparative analysis (17 patients in control group).