Проект системы оборотного водоснабжения для охлаждения гальванических ванн

Объект разработки: Кожухотрубчатый теплообменник. Цель работы: Рассчитать теплообменник для охлаждения оборотной воды. В ходе выполнения работы: Выполнены все необходимые расчеты для конструирования аппарата. Определены размеры и основные механические характеристики. Основные конструктивные, технологические и технико-эксплуатационные характеристики: Диаметр аппарата 159 мм, длина теплообменных труб 3 м, диаметр труб 25х2 мм, рабочее давление трубного пространства 0,2Development object: Shell and tube heat exchanger. Purpose of work: Calculate a heat exchanger for cooling the circulating water. In the course of the work: All the necessary calculations for the design of the apparatus have been completed. The dimensions and main mechanical characteristics are determined. The main design, technological and technical and operational characteristics: The diameter of the apparatus is 159 mm, the length of the heat exchange tubes is 3 m, the diameter of the tube

Heterogeneous treatment effects of therapeutic-dose heparin in patients hospitalized for COVID-19

Importance Randomized clinical trials (RCTs) of therapeutic-dose heparin in patients hospitalized with COVID-19 produced conflicting results, possibly due to heterogeneity of treatment effect (HTE) across individuals. Better understanding of HTE could facilitate individualized clinical decision-making. Objective To evaluate HTE of therapeutic-dose heparin for patients hospitalized for COVID-19 and to compare approaches to assessing HTE. Design, Setting, and Participants Exploratory analysis of a multiplatform adaptive RCT of therapeutic-dose heparin vs usual care pharmacologic thromboprophylaxis in 3320 patients hospitalized for COVID-19 enrolled in North America, South America, Europe, Asia, and Australia between April 2020 and January 2021. Heterogeneity of treatment effect was assessed 3 ways: using (1) conventional subgroup analyses of baseline characteristics, (2) a multivariable outcome prediction model (risk-based approach), and (3) a multivariable causal forest model (effect-based approach). Analyses primarily used bayesian statistics, consistent with the original trial. Exposures Participants were randomized to therapeutic-dose heparin or usual care pharmacologic thromboprophylaxis. Main Outcomes and Measures Organ support–free days, assigning a value of −1 to those who died in the hospital and the number of days free of cardiovascular or respiratory organ support up to day 21 for those who survived to hospital discharge; and hospital survival. Results Baseline demographic characteristics were similar between patients randomized to therapeutic-dose heparin or usual care (median age, 60 years; 38% female; 32% known non-White race; 45% Hispanic). In the overall multiplatform RCT population, therapeutic-dose heparin was not associated with an increase in organ support–free days (median value for the posterior distribution of the OR, 1.05; 95% credible interval, 0.91-1.22). In conventional subgroup analyses, the effect of therapeutic-dose heparin on organ support–free days differed between patients requiring organ support at baseline or not (median OR, 0.85 vs 1.30; posterior probability of difference in OR, 99.8%), between females and males (median OR, 0.87 vs 1.16; posterior probability of difference in OR, 96.4%), and between patients with lower body mass index (BMI 90% for all comparisons). In risk-based analysis, patients at lowest risk of poor outcome had the highest propensity for benefit from heparin (lowest risk decile: posterior probability of OR >1, 92%) while those at highest risk were most likely to be harmed (highest risk decile: posterior probability of OR <1, 87%). In effect-based analysis, a subset of patients identified at high risk of harm (P = .05 for difference in treatment effect) tended to have high BMI and were more likely to require organ support at baseline. Conclusions and Relevance Among patients hospitalized for COVID-19, the effect of therapeutic-dose heparin was heterogeneous. In all 3 approaches to assessing HTE, heparin was more likely to be beneficial in those who were less severely ill at presentation or had lower BMI and more likely to be harmful in sicker patients and those with higher BMI. The findings illustrate the importance of considering HTE in the design and analysis of RCTs. Trial Registration ClinicalTrials.gov Identifiers: NCT02735707, NCT04505774, NCT04359277, NCT0437258

Recruitment of monocytes and mature macrophages in mouse pubic symphysis relaxation during pregnancy and postpartum recovery

Appropriate remodeling of the female lower reproductive tract and pelvic floor is essential during normal mammalian pregnancy, labor, and postpartum recovery. During mouse pregnancy, in addition to reproductive tract modifications, the pubic symphysis (PS) is remodeled into a soft interpubic ligament (IpL) to provide safe delivery of the offspring and fast postpartum recovery. Although temporal changes in the phenotypes of myeloid cells, such as mononuclear phagocytes, are crucial to remodeling the lower reproductive tract organs in preparation for a safe delivery, little is known about the involvement of recruited monocytes or macrophages inmouse PS remodeling. We used combined light microscopy, electron microscopy, and qPCR analysis to investigate the profile of recruited monocytes and macrophage polarization markers in C57Bl6 mouse interpubic tissues during pregnancy (D12, D18, and D19) and early days postpartum (1 dpp and 3 dpp) to better identify their presence in proper remodeling of the mouse PS. Our morphological data show that the number of recruited monocytes is increased in interpubic tissues and that recruited monocytes differentiate into proinflammatory or anti-inflammatory macrophage phenotypes from D18 to 3 dpp, which may contribute to dynamic changes in the gene expression of specific inflammatory mediators involved in interpubic tissue remodeling at these time points. Therefore, our morphological and quantitative gene expression data suggest that both differentiated macrophages from recruited monocytes and polarized macrophages may collaborate for IpL relaxation at labor and the appropriate repair of the PS after the first pregnancy. Summary Sentence Recruited monocytes and mature macrophages are present in the mouse pubic symphysis and may contribute to mouse pubic symphysis relaxation during late pregnancy and postpartum recovery1012466477CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP140714/2016-2; 302208/2017-82012/25038-8; 2015/23616-

The involvement of mast cells in the irinotecan-induced enteric neurons loss and reactive gliosis

Abstract Background The irinotecan (CPT-11) causes intestinal mucositis and diarrhea that may be related to changes in the enteric nervous system (ENS). In inflammatory condition, mast cells release a variety of pro-inflammatory mediators that can interact with the ENS cells. It has not been explored whether CPT-11 is able to alter the enteric glial and neuronal cell, and the role of mast cells in this effect. Therefore, this study was conducted to investigate the effect of CPT-11 on the enteric glial and neuronal cells, as well as to study the role of mast cells in the CPT-11-induced intestinal mucositis. Methods Intestinal mucositis was induced in Swiss mice by the injection of CPT-11 (60 mg/kg, i.p.) once a day for 4 days following by euthanasia on the fifth day. To investigate the role of mast cells, the mice were pretreated with compound 48/80 for 4 days (first day, 0.6 mg/kg; second day, 1.0 mg/kg; third day, 1.2 mg/kg; fourth day, 2.4 mg/kg) to induce mast cell degranulation before the CPT-11 treatment. Results Here, we show that CPT-11 increased glial fibrillary acidic protein (GFAP) and S100β gene and S100β protein expressions and decreased HuC/D protein expression in the small intestine segments. Concomitantly, CPT-11 enhanced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels and inducible nitric oxide synthase (iNOS) gene expression, associated with an increase in the total number macrophages (positive cells for ionized calcium-binding adapter molecule, Iba-1) and degranulated mast cells in the small intestine segments and caused significant weight loss. The pretreatment with compound 48/80, an inductor of mast cells degranulation, significantly prevented these CPT-11-induced effects. Conclusions Our data suggests the participation of mast cells on the CPT-11-induced intestinal mucositis, macrophages activation, enteric reactive gliosis, and neuron loss

Oral administration of EPA-rich oil impairs collagen reorganization due to elevated production of IL-10 during skin wound healing in mice

Wound healing is an essential process for organism survival. Some fatty acids have been described as modulators of wound healing. However, the role of omega-3 fatty acids is unclear. In the present work, we investigate the effects of oral administration of eicosapentaenoic acid (EPA)-rich oil on wound healing in mice. After 4 weeks of EPA-rich oil supplementation (2 g/kg of body weight), mice had increased serum concentrations of EPA (20:5ω-3) (6-fold) and docosahexaenoic acid (DHA; 22:6ω-3) (33%) in relation to control mice. Omega-3 fatty acids were also incorporated into skin in the EPA fed mice. The wound healing process was delayed at the 3rd and 7th days after wounding in mice that received EPA-rich oil when compared to control mice but there was no effect on the total time required for wound closure. Collagen reorganization, that impacts the quality of the wound tissue, was impaired after EPA-rich oil supplementation. These effects were associated with an increase of M2 macrophages (twice in relation to control animals) and interleukin-10 (IL-10) concentrations in tissue in the initial stages of wound healing. In the absence of IL-10 (IL-10−/− mice), wound closure and organization of collagen were normalized even when EPA was fed, supporting that the deleterious effects of EPA-rich oil supplementation were due to the excessive production of IL-10. In conclusion, oral administration of EPA-rich oil impairs the quality of wound healing without affecting the wound closure time likely due to an elevation of the anti-inflammatory cytokine IL-10