PATHOGENETIC ASPECTS OF INFERTILITY IN WOMEN OF REPRODUCTIVE AGE WITH OVARIAN VARICOCELE

To date, the problem of reduced fertility is quite relevant. At the same time, it should be noted that the effectiveness of infertility treatment, even with the use of the latest techniques, tools and drugs does not exceed 35-40%. This can be explained by insufficient study of a number of causes that lead to impaired fertility.One of these little-known and poorly studied factors is pelvic venous plethora, in particular varicose veins of the ovaries. While anatomically similar disease in men - varicocele - is given great importance, in women, even the very existence of this pathology is controversial among some authors.All studies were conducted in compliance with the basic bioethical norms and requirements of the Declaration of Helsinki. 117 women of reproductive age (21 - 42 years) with infertility of functional genesis were examined.According to the results of the analysis, the clinical and anamnestic features of women with infertility and ovaric varicocele are increased proportion of patients with intellectual differentiation and psycho-emotional and physical stress, high frequency of infectious diseases with acyclic uterine bleeding, dysmenorrhea and premenstrual. Changes in the anatomical and functional state of the pelvic organs and venous system in women with infertility and ovarian varicocele have been established. It was found that the hormonal profile of women with infertility and ovarian varicocele is characterized by a decrease in estradiol and progesterone. A pathogenetically sound algorithm for the diagnosis and treatment of women with infertility and ovarian varicocele has been developed, which is based on clinical data and the results of instrumental methods of examination.To date, the problem of reduced fertility is quite relevant. At the same time, it should be noted that the effectiveness of infertility treatment, even with the use of the latest techniques, tools and drugs does not exceed 35-40%. This can be explained by insufficient study of a number of causes that lead to impaired fertility.One of these little-known and poorly studied factors is pelvic venous plethora, in particular varicose veins of the ovaries. While anatomically similar disease in men - varicocele - is given great importance, in women, even the very existence of this pathology is controversial among some authors.All studies were conducted in compliance with the basic bioethical norms and requirements of the Declaration of Helsinki. 117 women of reproductive age (21 - 42 years) with infertility of functional genesis were examined.According to the results of the analysis, the clinical and anamnestic features of women with infertility and ovaric varicocele are increased proportion of patients with intellectual differentiation and psycho-emotional and physical stress, high frequency of infectious diseases with acyclic uterine bleeding, dysmenorrhea and premenstrual. Changes in the anatomical and functional state of the pelvic organs and venous system in women with infertility and ovarian varicocele have been established. It was found that the hormonal profile of women with infertility and ovarian varicocele is characterized by a decrease in estradiol and progesterone. A pathogenetically sound algorithm for the diagnosis and treatment of women with infertility and ovarian varicocele has been developed, which is based on clinical data and the results of instrumental methods of examination

Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation.

The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 Å using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation

Structure of a putative NTP pyrophosphohydrolase: YP_001813558.1 from Exiguobacterium sibiricum 255-15.

The crystal structure of a putative NTPase, YP_001813558.1 from Exiguobacterium sibiricum 255-15 (PF09934, DUF2166) was determined to 1.78 Å resolution. YP_001813558.1 and its homologs (dimeric dUTPases, MazG proteins and HisE-encoded phosphoribosyl ATP pyrophosphohydrolases) form a superfamily of all-α-helical NTP pyrophosphatases. In dimeric dUTPase-like proteins, a central four-helix bundle forms the active site. However, in YP_001813558.1, an unexpected intertwined swapping of two of the helices that compose the conserved helix bundle results in a `linked dimer' that has not previously been observed for this family. Interestingly, despite this novel mode of dimerization, the metal-binding site for divalent cations, such as magnesium, that are essential for NTPase activity is still conserved. Furthermore, the active-site residues that are involved in sugar binding of the NTPs are also conserved when compared with other α-helical NTPases, but those that recognize the nucleotide bases are not conserved, suggesting a different substrate specificity

Correlation between actual nutrition and lipid peroxidation and antioxidant defense parameters in aged 14–17 years adolescents living in rural area

The aim of the study was to reveal the relationship between the parameters of actual nutrition and the lipid peroxidation and antioxidant defense system in adolescents aged 14–17 in a rural area. Material and methods. 76 adolescents aged 14–17 of the Irkutsk region were examined by the cross-sectional study method. Actual nutrition was studied by the 24-hour nutrition reproduction method. The content of substrates with unsaturated double bonds (DB), diene conjugates (DC), ketodienes and conjugated trienes (KD and CT), thiobarbituric acid reacting species (TBARS), α-tocopherol, retinol, reduced (GSH) and oxidized glutathione (GSSG), total blood antioxidant activity (TAA), superoxide dismutase (SOD) activity in blood by spectrophotometry and fluorometry methods were analyzed. Results. The adolescents’ diet did not meet the principles of a balanced diet – there was reduced protein intake, an imbalance of unsaturated fatty acids, A, C, D, B vitamins deficiency. An excessive element in the diet was sodium. The content of substrates with DB, KD and CT and TBARS increased significantly in the studied group of adolescents, the concentration of DC decreased. Parameters of antioxidant defense both decreased (TAA, retinol content) and increased (α-tocopherol, GSH concentration). Correlation analysis showed relationships between DB and vitamin B1, B2 content; DC level and calories, carbohydrate and vitamin B1 content; concentration of KD and CT and fats, TAA and vitamin A and β-carotene level; level of α-tocopherol in blood and vitamin E in food; GSH and vitamin K; SOD activity and vitamin H content. Multiple negative correlations were between GSSG and fat, vitamins B1, B9, C, K food concentration were found.Conclusions. The calculated vitamin consumption indicators allow to reveal nutritional deviations in adolescents and to connect them with the real provision of the body with these metabolites

Comparison of REMS, NEWS, qSOFA and SIRS criteria scales for sepsis prediction in patients with diagnosis “SARS-CoV-2, virus unidentified”: a retrospective observational study

Background. Despite ample research on the coronavirus infection sequence and therapy, the incidence of adverse outcomes remains very high. Sepsis stands among the major factors greatly complicating treatment and increasing the risk of death. A timely identification of highrisk sepsis patients is a cornerstone of effective sepsis prevention.Objectives. A comparative prognostic power assessment between the quick Sequential Organ Failure Assessment (qSOFA) scale, National Early Warning Score (NEWS), Initial Prehospital Rapid Emergency Medicine Score (REMS) and the Systemic Inflammatory Response Syndrome (SIRS) criteria for sepsis detection in anaesthetic intensive care patients with a diagnosis: SARS-CoV-2, virus unidentified.Methods. A retrospective observational study included 166 patients over 18-year age with unconfirmed infection (ICD-10 code U07.2). The qSOFA, NEWS, REMS and SIRS point estimates were obtained from each patient. The patients were retrospectively divided in two cohorts by sepsis presence (Sepsis-3 criteria) to determine the express scales power in evaluating the risk of sepsis (estimated as area under ROC curve, AUROC).Results. Data on 102 patients were included in the final analysis. Fifty-eight (57%) patients were terminal, and 55 (54%) developed sepsis. The estimates are as follows: NEWS — AUROC 0.848 [95% confidence interval (CI) 0.764–0.912], sensitivity 76.36% [95% CI 63.0–86.8], specificity 82.98% [95% CI 69.2–92.4], optimal cut-off threshold >5 points; qSOFA — AUROC 0.700 [95% CI 0.602–0.787], sensitivity 76.36% [95% CI 63.0–86.8], specificity 61.70% [95% CI 46.4–75.5], optimal cut-off threshold >0 points; REMS — AUROC 0.739 [95% CI 0.643–0.821], sensitivity 69.09% [95% CI 55.2–80.9], specificity 65.96% [95% CI 50.7–79.1], optimal cut-off threshold >5 points; SIRS criteria — AUROC 0.723 [95% CI 0.626–0.807], sensitivity 98.18% [95% CI 90.3–100.0], specificity 31.91% [95% CI 19.1–47.1], optimal cut-off threshold >0 points.Conclusion. The NEWS scale revealed a good prognostic power to estimate the risk of sepsis in patients with suspected COVID-19 disease. The qSOFA, REMS scales and SIRS criteria possess a good calibration capacity, albeit insufficient resolution, which limits their prognostic value

Structure of the γ-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases.

Dipeptidyl-peptidase VI from Bacillus sphaericus and YkfC from Bacillus subtilis have both previously been characterized as highly specific γ-D-glutamyl-L-diamino acid endopeptidases. The crystal structure of a YkfC ortholog from Bacillus cereus (BcYkfC) at 1.8 Å resolution revealed that it contains two N-terminal bacterial SH3 (SH3b) domains in addition to the C-terminal catalytic NlpC/P60 domain that is ubiquitous in the very large family of cell-wall-related cysteine peptidases. A bound reaction product (L-Ala-γ-D-Glu) enabled the identification of conserved sequence and structural signatures for recognition of L-Ala and γ-D-Glu and, therefore, provides a clear framework for understanding the substrate specificity observed in dipeptidyl-peptidase VI, YkfC and other NlpC/P60 domains in general. The first SH3b domain plays an important role in defining substrate specificity by contributing to the formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed. A conserved tyrosine in the SH3b domain of the YkfC subfamily is correlated with the presence of a conserved acidic residue in the NlpC/P60 domain and both residues interact with the free amine group of the alanine. This structural feature allows the definition of a subfamily of NlpC/P60 enzymes with the same N-terminal substrate requirements, including a previously characterized cyanobacterial L-alanine-γ-D-glutamate endopeptidase that contains the two key components (an NlpC/P60 domain attached to an SH3b domain) for assembly of a YkfC-like active site

Clinical and epidemiological characteristics and effectiveness of antiviral therapy for COVID-19 in children: The experience of the first year of the pandemic

Background. The use of antiviral agents can shorten the duration of the viral infection. The aim: to study the clinical and epidemiological features and the effectiveness of antiviral therapy for new coronavirus infection (COVID-19) in outpatient children.Materials and methods. From April 2020 to March 2021, 9334 outpatient children aged from 0 months to 17 years were randomly tested for new coronavirus infection. SARS-CoV-2 RNA was detected in oropharyngeal and nasal material by PCR. Patients with confirmed new coronavirus infection were prescribed interferon-alpha (IFN-α) intranasally, antiviral agents of systemic action. The control group consisted of children with COVID-19 who did not receive treatment.Results. When examining clinically healthy contact children, SARS-CoV-2 RNA was detected in 7.4 % of cases. In the structure of ARI, the specific weight of COVID-19 was 12.3 % with the peak incidence in April-May (up to 22.8 %) and NovemberDecember (up to 30.0 %). In half of the cases, children became infected in the family, and usually adults were the index patient. In 47.7 % of cases, an asymptomatic form of COVID-19 was registered without significant differences in patients of different ages. In one third of children with concomitant pathology, the disease was asymptomatic, in half it was mild, in other cases moderate severity was diagnosed. The clinical picture of COVID-19 did not differ from other ARIs. Anosmia (9.4 %) in half of the cases was combined with ageusia (4.4 %) and was significantly more common in boys. The duration of clinical manifestations in children of the control group and those who received antiviral therapy did not statistically significantly differ in mild and severity of the disease. Also, various antiviral therapy options did not significantly affect the duration of SARS-CoV-2 detection in children with various forms of COVID-19.Conclusion. In the first year of the pandemic, the novel coronavirus infection did not dominate the pattern of respiratory diseases in outpatient children. Further research is required to develop pediatric guidelines for the treatment of COVID-19 at the outpatient stage

The structure of BVU2987 from Bacteroides vulgatus reveals a superfamily of bacterial periplasmic proteins with possible inhibitory function.

Proteins that contain the DUF2874 domain constitute a new Pfam family PF11396. Members of this family have predominantly been identified in microbes found in the human gut and oral cavity. The crystal structure of one member of this family, BVU2987 from Bacteroides vulgatus, has been determined, revealing a β-lactamase inhibitor protein-like structure with a tandem repeat of domains. Sequence analysis and structural comparisons reveal that BVU2987 and other DUF2874 proteins are related to β-lactamase inhibitor protein, PepSY and SmpA_OmlA proteins and hence are likely to function as inhibitory proteins

cisRED: a database system for genome-scale computational discovery of regulatory elements

We describe cisRED, a database for conserved regulatory elements that are identified and ranked by a genome-scale computational system (). The database and high-throughput predictive pipeline are designed to address diverse target genomes in the context of rapidly evolving data resources and tools. Motifs are predicted in promoter regions using multiple discovery methods applied to sequence sets that include corresponding sequence regions from vertebrates. We estimate motif significance by applying discovery and post-processing methods to randomized sequence sets that are adaptively derived from target sequence sets, retain motifs with p-values below a threshold and identify groups of similar motifs and co-occurring motif patterns. The database offers information on atomic motifs, motif groups and patterns. It is web-accessible, and can be queried directly, downloaded or installed locally

Сердечно-легочная реанимация у больных с ожирением

Objective: an analysis of literature covering the effects of morbid obesity on various aspects of cardiopulmonary resuscitation (CPR) and its outcomes. Currently, there is no specific standard for CPR in morbidly obese patients (body mass index ≤ 30). Significant constitutional, anatomical, and physiological factors can lead to negative treatment outcomes in people with significant  excess weight. The review presents study results evaluating the effectiveness of the essential components of CPR in obese patients. In particular, it discusses issues of indirect cardiac massage and defibrillation, airway management and ventilation, venous access, and pharmacokinetics of drugs used during CPR. It demonstrates that CPR in obese patients has its own characteristics not mentioned in official recommendations and guidelines.Цель обзора: проанализировать имеющиеся в литературе данные о влиянии ожирения на различные аспекты проведения и исход мероприятий сердечно-легочной реанимации (СЛР). В настоящее время не существует особого стандарта проведения СЛР для пациентов с ожирением (избыточное или патологическое накопление жира с повышением индекса массы тела ≤ 30). Однако наличие у людей с избыточной массой тела значимых конституционально-анатомических и физиологических особенностей может явиться существенным фактором, способным негативно влиять как на ее проведение, так и на результат. Приведены результаты исследований, посвященных оценке эффективности применения наиболее существенных компонентов СЛР у больных с ожирением. Рассмотрены, в частности, вопросы проведения непрямого массажа и дефибрилляции, обеспечения проходимости дыхательных путей и вентиляции, обеспечения венозного доступа, фармакокинетики лекарственных средств, используемых во время СЛР. Показано, что проведение СЛР у пациентов с ожирением имеет свои особенности, которые пока не находят отражения в официальных документах и рекомендациях, но которые необходимо знать