Pregnancy induced TMA in severe preeclampsia results from complement-mediated thromboinflammation

Preeclampsia is a multifactorial vascular disease unique to human pregnancy. While genetic and antiangiogenic factors are important contributors to preeclampsia susceptibility, recent studies have shown that dysregulation and/or over-activation of the complement system has an integral role in dis-ease etiology. Furthermore, the role of the coagulation cascade may be underappreciated in the develop-ment of the disease. Traditionally, for research purposes, the pool of preeclampsia cases has been divided into non-severe and severe disease depending on the onset and severity of the symptoms. However, of particular interest are a small but important minority of cases that present with symptoms likening to those of hemolysis, elevated liver enzymes and low platelets syndrome, atypical hemolytic uremic syn-drome, or thrombotic thrombocytopenic purpura, all thrombotic microangiopathy (TMA) diseases, with the hallmark mechanisms of endothelial dysfunction and aberrant activation of complement and coagu-lation cascades. We therefore propose a third class, severe TMA-like preeclampsia to be included in the categorization of preeclampsia patients. Identifying these patients would target research, diagnostic dif-ferentiation, and novel treatment options to the subclass of patients with life-threatening disease that are most likely to benefit from next-generation drug development. (c) 2021 The Authors. Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).Peer reviewe

Achieving equity through 'gender autonomy': the challenges for VET policy and practice

This paper is based on research carried out in an EU Fifth Framework project on 'Gender and Qualification'. The research partners from five European countries investigated the impact of gender segregation in European labour markets on vocational education and training, with particular regard to competences and qualifications. The research explored the part played by gender in the vocational education and training experiences of (i) young adults entering specific occupations in child care, electrical engineering and food preparation/service (ii) adults changing occupations

NMR Structure Determinations of Small Proteins Using only One Fractionally 20% 13C- and Uniformly 100% 15N-Labeled Sample

Uniformly 13C- and 15N-labeled samples ensure fast and reliable nuclear magnetic resonance (NMR) assignments of proteins and are commonly used for structure elucidation by NMR. However, the preparation of uniformly labeled samples is a labor-intensive and expensive step. Reducing the portion of 13C-labeled glucose by a factor of five using a fractional 20% 13C- and 100% 15N-labeling scheme could lower the total chemical costs, yet retaining sufficient structural information of uniformly [13C, 15N]-labeled sample as a result of the improved sensitivity of NMR instruments. Moreover, fractional 13C-labeling can facilitate reliable resonance assignments of sidechains because of the biosynthetic pathways of each amino-acid. Preparation of only one [20% 13C, 100% 15N]-labeled sample for small proteins

Diabetes Care for Patients with Peripheral Arterial Disease

The number of diabetics will increase almost 70% in developed countries during the next 20 years: peripheral arterial disease is a common and costly complication. The incidence of cardiovascular disease (mortality and morbidity) due to atherosclerosis, is higher among patients with diabetes than in those without diabetes. Intensive management of diabetes, including glycaemic control, treatment of hypertension and dyslipidemia, as well as nonpharmacological interventions, decreases both micro- and macrovascular complications. Aspirin and clopidogrel have less antiplatelet effect in patients with diabetes. Metformin therapy is considered a risk factor for lactic acidosis if not withdrawn 2 days before angiography, but this risk is extremely low in patients with normal renal function. Peri-operative hyperglycaemia and large fluctuations in plasma glucose increase postoperative mortality and morbidity and careful measures are required to minimise these effects

Electric-driven Zonal Hydraulics in Non-Road Mobile Machinery

The goal of this research is to apply direct-driven hydraulics (DDH) to the concept of zonal (i.e., locally and operation-focused) hydraulics, which is an essential step in the hybridization and automation of machines. DDH itself aims to combine the best properties of electric and hydraulic technologies and will lead to increased productivity, minimized energy consumption and higher robust performance in both stationary and mobile machines operating in various environments. In the proposed setup, the speed and position control of a double-acting cylinder is implemented directly with an electric motor drive in a closed-loop system without conventional control valves and an oil tank. The selection of the location of the hydraulic accumulator and connection of the external leakage lines will also be part of this study. Simulations and experimental research to study the details of the hydromechanical and electrical realization of the DDH are performed

Eculizumab Treatment for Postpartum HELLP Syndrome and aHUS—Case Report

Preeclampsia is a pregnancy-specific disorder affecting ca 3% of all pregnant women. Preeclampsia is the source of severe pregnancy complications. Later life consequences for mother and infant include increased risk of cardiovascular disease. Preeclampsia is caused by the dysfunction of the endothelium with subsequent activation of complement and coagulation systems. HELLP syndrome is considered to be an extreme complication of preeclampsia but it can also present independently. Diagnostic symptoms in HELLP syndrome are Hemolysis, Elevated Liver enzymes, and Low Platelets. Similar phenotype is present in thrombotic microangiopathies (TMAs) and HELLP syndrome is considered part of the TMA spectrum. Here, we present a case of severe preeclampsia and HELLP syndrome, which exacerbated rapidly and eventually led to need of intensive care, plasma exchange, and hemodialysis. The patient showed signs of hemolysis, disturbance in the coagulation, and organ damage in liver and kidneys. After comprehensive laboratory testing and supportive care, the symptoms did not subside and treatment with complement C5 inhibitor eculizumab was started. Thereafter, the patient started to recover. The patient had pregnancy-induced aHUS. Earlier initiation of eculizumab treatment may potentially shorten and mitigate the disease and hypothetically decrease future health risks of preeclamptic women.Peer reviewe

NMR Structure Determinations of Small Proteins Using only One Fractionally 20% 13C- and Uniformly 100% 15N-Labeled Sample

Uniformly 13C- and 15N-labeled samples ensure fast and reliable nuclear magnetic resonance (NMR) assignments of proteins and are commonly used for structure elucidation by NMR. However, the preparation of uniformly labeled samples is a labor-intensive and expensive step. Reducing the portion of 13C-labeled glucose by a factor of five using a fractional 20% 13C- and 100% 15N-labeling scheme could lower the total chemical costs, yet retaining sufficient structural information of uniformly [13C, 15N]-labeled sample as a result of the improved sensitivity of NMR instruments. Moreover, fractional 13C-labeling can facilitate reliable resonance assignments of sidechains because of the biosynthetic pathways of each amino-acid. Preparation of only one [20% 13C, 100% 15N]-labeled sample for small proteins