Септический шок у взрослых: клинические рекомендации Общероссийской общественной организации «Федерация анестезиологов и реаниматологов»

В статье представлены основные положения клинических рекомендаций по септическому шоку у взрослых, утвержденных Общероссийской общественной организацией «Федерация анестезиологов и реаниматологов» в 2023 г. Актуальность проблемы связана со значительной распространенностью и высокими показателями летальности при септическом шоке. Рекомендации включают вопросы этиологии, патогенеза, клинической картины, методов лабораторной и инструментальной диагностики септического шока. Представлена стартовая интенсивная терапия септического шока, включая подходы по назначению вазопрессорных и инотропных препаратов, рекомендации по выбору антибактериальных препаратов, особенности инфузионной и адъювантной терапии, в том числе при рефрактерном к терапии септическом шоке. Обсуждены вопросы хирургического лечения очага инфекции. Представлены критерии качества оказания медицинской помощи взрослым пациентам с септическим шоком и алгоритмы действий врача при диагностике и интенсивной терапии пациентов с септическим шоком

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Molecular Genetic Markers for Birds Evolutionary and Population Research

Research and protection of large predatory birds have faced difficulties because of the problem of determining the actual species status of individuals of the studied population or population’s group. In biology, the concept of the species was a subject of debates during the last century. There are many problems associated with the definition of species status. These problems include uncertainty due to presence of parthenogenetic species, and the presence of various forms and morphs with different degrees of relationship and different degrees of isolation. The problems are also related with the possibilities of rapid removal, or “opening” of isolating barriers between forms, and vice versa, their instantaneous formation, for example, under the influence of intracellular parasites / symbionts. The existence of populations and morphotypes with different degree of isolation and kinship is typical for birds because of their ability to long distance migration. What formal criteria and methodological approaches can we use to evaluate the species and population diversity of birds, as well as the threat of their depletion and extinction

Handling of Multiple‐Wave Effects in the Measurement of Forbidden X‐Ray Reflections in TeO2_2

Multiple-wave X-ray reflections usually aggravate the measurement of Bragg reflections, especially of weak “forbidden” reflections. Accurate analysis of multiple-wave peaks usually allows to avoid this. However, multiple-wave reflections can also provide information about crystal structure, since crystal cell parameters determine the positions of multi-wave peaks. The forbidden reflections 002 and 100 in paratellurite are measured and an approach based on semi-kinematical X-ray scattering used to handle the multiple-wave interferences is shown here

Handling of Multiple‐Wave Effects in the Measurement of Forbidden X‐Ray Reflections in TeO 2

Multiple-wave X-ray reflections usually aggravate the measurement of Bragg reflections, especially of weak “forbidden” reflections. Accurate analysis of multiple-wave peaks usually allows to avoid this. However, multiple-wave reflections can also provide information about crystal structure, since crystal cell parameters determine the positions of multi-wave peaks. The forbidden reflections 002 and 100 in paratellurite are measured and an approach based on semi-kinematical X-ray scattering used to handle the multiple-wave interferences is shown here

Proteasome functioning in breast cancer: connection with clinical-pathological factors.

Breast cancer is one of four oncology diseases that are most widespread in the world. Moreover, breast cancer is one of leading causes of cancer-related deaths in female population within economically developed regions of the world. So far, detection of new mechanisms of breast cancer development is very important for discovery of novel areas in which therapy approaches may be elaborated. The objective of the present study is to investigate involvement of proteasomes, which cleave up to 90% of cellular proteins and regulate numerous cellular processes, in mechanisms of breast cancer development. Proteasome characteristics in 106 patient breast carcinomas and adjacent tissues, as well as relationships of detected proteasome parameters with clinical-pathological factors, were investigated. Proteasome chymotrypsin-like activity was evaluated by hydrolysis of fluorogenic peptide Suc-LLVY-AMC. The expression of proteasome subunits was studied by Western-blotting and immunohistochemistry. The wide range of chymotrypsin-like activity in tumors was detected. Activity in tumors was higher if compared to adjacent tissues in 76 from 106 patients. Multiple analysis of generalized linear models discovered that in estrogen α-receptor absence, tumor growth was connected with the enhanced expression of proteasome immune subunit LMP2 and proteasome activator PA700 in tumor (at 95% confidence interval). Besides, by this analysis we detected some phenomena in adjacent tissue, which are important for tumor growth and progression of lymph node metastasis in estrogen α-receptor absence. These phenomena are related to the enhanced expression of activator PA700 and immune subunit LMP7. Thus, breast cancer development is connected with functioning of immune proteasome forms and activator PA700 in patients without estrogen α-receptors in tumor cells. These results could indicate a field for search of new therapy approaches for this category of patients, which has the worst prognosis of health recovery

Proteasomes in Patient Rectal Cancer and Different Intestine Locations: Where Does Proteasome Pool Change?

A special problem in the surgery of rectal cancer is connected with a need for appropriate removal of intestine parts, along with the tumor, including the fragment close to the sphincter. To determine the length of fragments to remove, it is necessary to reveal areas without changes in molecule functioning, specific for tumor. The purpose of the present study was to investigate functioning the proteasomes, the main actors in protein hydrolysis, in patient rectal adenocarcinoma and different intestine locations. Chymotrypsin-like and caspase-like activities, open to complex influence of different factors, were analyzed in 43–54 samples by Suc-LLVY-AMC- and Z-LLE-AMC-hydrolysis correspondingly. Both activities may be arranged by the decrease in the location row: cancer→adjacent tissue→proximal (8–20 cm from tumor) and distal (2 and 4 cm from tumor) sides. These activities did not differ noticeably in proximal and distal locations. Similar patterns were detected for the activities and expression of immune subunits LMP2 and LMP7 and expression of 19S and PA28αβ activators. The largest changes in tumor were related to proteasome subtype containing LMP2 and PA28αβ that was demonstrated by native electrophoresis. Thus, the results indicate a significance of subtype LMP2-PA28αβ for tumor and absence of changes in proteasome pool in distal fragments of 2–4 cm from tumor

4-methylumbelliferone Prevents Liver Fibrosis by Affecting Hyaluronan Deposition, FSTL1 Expression and Cell Localization

4-methylumbelliferone (4MU) is an inhibitor of hyaluronan deposition and an active substance of hymecromone, a choleretic and antispasmodic drug. 4MU reported to be anti-fibrotic in mouse models; however, precise mechanism of action still requires further investigation. Here we describe the cellular and molecular mechanisms of 4MU action on CCl4-induced liver fibrosis in mice using NGS transcriptome, Q-PCR and immunohistochemical analysis. Collagen and hyaluronan deposition were prevented by 4MU. The CCl4 stimulated expression of Col1a and αSMA were reduced, while the expression of the ECM catabolic gene Hyal1 was increased in the presence of 4MU. Bioinformatic analysis identified an activation of TGF-beta and Wnt/beta-catenin signaling pathways, and inhibition of the genes associated with lipid metabolism by CCL4 treatment, while 4MU restored key markers of these pathways to the control level. Immunohistochemical analysis reveals the suppression of hepatic stellate cells (HSCs) transdifferentiation to myofibroblasts by 4MU treatment. The drug affected the localization of HSCs and macrophages in the sites of fibrogenesis. CCl4 treatment induced the expression of FSTL1, which was downregulated by 4MU. Our results support the hypothesis that 4MU alleviates CCl4-induced liver fibrosis by reducing hyaluronan deposition and downregulating FSTL1 expression, accompanied by the suppression of HSC trans-differentiation and altered macrophage localization

Structure, Energy, and Vibrational Frequencies of Oxygen Allotropes On (n ≤ 6) in the Covalently Bound and van der Waals Forms: Ab Initio Study at the CCSD(T) Level

Recent experiments on the UV and electron beam irradiation of solid O2 reveals a series of IR features near the valence antisymmetric vibration band of O3 which are frequently interpreted as the formation of unusual On allotropes in the forms of weak complexes or covalently bound molecules. In order to elucidate the question of the nature of the irradiation products, the structure, relative energies, and vibrational frequencies of various forms of On (n = 1−6) in the singlet, triplet, and, in some cases, quintet states were studied using the CCSD(T) method up to the CCSD(T,full)/cc-pCVTZ and CCSD(T,FC)/aug-cc-pVTZ levels. The results of calculations demonstrate the existence of stable highly symmetric structures O4(D3h), O4 (D2d), and O6 (D3d) as well as the intermolecular complexes O2·O2, O2·O3, and O3·O3 in different conformations. The calculations show that the local minimum corresponding to the O3···O complex is quite shallow and cannot explain the ν3 band features close to 1040 cm−1, as was proposed previously. For the ozone dimer, a new conformer was found which is more stable than the structure known to date. The effect of the ozone dimer on the registered IR spectra is discussed