COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

The role of shear stress on ET-1, KLF2, and NOS-3 expression in the developing cardiovascular system of chicken embryos in a venous ligation model

In this review, the role of wall shear stress in the chicken embryonic heart is analyzed to determine its effect on cardiac development through regulating gene expression. Therefore, background information is provided for fluid dynamics, normal chicken and human heart development, cardiac malformations, cardiac and vitelline blood flow, and a chicken model to induce cardiovascular anomalies. A set of endothelial shear stress-responsive genes coding for endothelin-1 (ET-1), lung Krüppel-like factor (LKLF/KLF2), and endothelial nitric oxide synthase (eNOS/NOS-3) are active in development and are specifically addresse

The endothelin-1 pathway and the development of cardiovascular defects in the haemodynamically challenged chicken embryo

Background/Aims: Ligating the right lateral vitelline vein of chicken embryos (venous clip) results in cardiovascular malformations. These abnormalities are similar to malformations observed in knockout mice studies of components of the endothelin-1 (ET-1)/endothelin-converting enzyme-1/endothelin-A receptor pathway. In previous studies we demonstrated that cardiac ET- 1 expression is decreased 3 h after clipping, and ventricular diastolic filling is disturbed after 2 days. Therefore, we hypothesise that ET-1-related processes are involved in the development of functional and morphological cardiovascular defects after venous clip. Methods: In this study, ET-1 and endothelin receptor antagonists (BQ123, BQ-788 and PD145065) were infused into the HH18 embryonic circulation. Immediate haemodynamic effects on the embryonic heart and extra-embryonic vitelline veins were examined by Doppler and micro-particle image velocimetry. Ventricular diastolic filling characteristics were studied at HH24, followed by cardiovascular morphologic investigation (HH35). Results: ET-1 and its receptor antagonists induced haemodynamic effects at HH18. At HH24, a reduced diastolic ventricular passive filling component was demonstrated, which was compensated by an increased active filling component. Thinner ventricular myocardium was shown in 42% of experimental embryos. Conclusion: We conclude that cardiovascular malformations after venous clipping arise from a combination of haemodynamic changes and altered gene expression patterns and levels, including those of the endothelin pathway

Expression of thrombospondin-1 (TSP-1) and signal-regulatory protein-alpha (SIRPα) by human articular chondrocytes and molecular associations of CD47/IAP

Protein extracts from primary cultures of human articular chondrocytes were separated by SDS-PAGE and immunoblotted with antibodies against TSP-1 and SIRPα. For TSP-1, a 6% gel under reducing conditions was used, whereas for SIRPα, an 8% gel under non-reducing conditions was used. Protein extracts from primary cultures of human articular chondrocytes were immunoprecipitated with antibodies against CD47/IAP and immunoblotted for TSP-1, SIRPα, or α5 integrin. TSP-1, SIRPα, and α5 integrin are identified in non-immunoprecipitated extracts, but only TSP-1 and α5 integrin co-immunoprecipitate with CD47/IAP. IP, immunoprecipitated protein extracts; MW, molecular weight; N, normal human articular chondrocytes; Non IP, non-immunoprecipitated protein extracts; OA, osteoarthritic human articular chondrocytes.<p><b>Copyright information:</b></p><p>Taken from "CD47 associates with alpha 5 integrin and regulates responses of human articular chondrocytes to mechanical stimulation in an model"</p><p>http://arthritis-research.com/content/10/1/R4</p><p>Arthritis Research & Therapy 2008;10(1):R4-R4.</p><p>Published online 10 Jan 2008</p><p>PMCID:PMC2374443.</p><p></p

Primary cilia sensitize endothelial cells for fluid shear stress

Primary cilia are mechanosensors for fluid shear stress, and are involved in a number of syndromes and congenital anomalies. We identified endothelial cilia in areas of low shear stress in the embryonic heart. The objective of the present study was to demonstrate the role of primary cilia in mechanosensing. Ciliated embryonic endothelial cells were cultured from the heart, and non-ciliated cells from the arteries. Non-ciliated cells that were subjected to fluid shear stress showed significantly less induction of the shear marker Krüppel-Like Factor-2, as compared to ciliated cells. In addition, ciliated cells from which the cilia were chemically removed show a similar decrease in flow response. This shows that primary cilia sensitize endothelial cells for fluid shear stress. In addition, we targeted and stabilized the connection of the cilium to the cytoplasm by treatment with Colchicine and Taxol/Paclitaxel, respectively, and show that microtubular integrity is essential to sense shear stres

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報告番号: ; 学位授与年月日: 2016-09-16 ; 学位の種別: 修士 ; 学位の種類: 修士(国際協力学) ; 学位記番号: 修創域第6139号 ; 研究科・専攻: 新領域創成科学研究科環境学研究系国際協力学専