Activiteit

Objectives Only two mutations at the lysine 183 amino acid in the extracellular N-terminal domain of human TSH receptor (hTSHR) have been associated with hypersensitivity to hCG and familial gestational hyperthyroidism. Design Describe a new variant of the TSHR gene with hCG hypersensitivity found in two women of the same family diagnosed with gestational hyperthyroidism. Patients A 38-year-old woman was seen during the first trimester of her second pregnancy for thyrotoxicosis with increased fT3 and fT4 concentrations and low TSH levels without anti-TSH receptor antibody. Thyrotoxicosis improved spontaneously during the 2nd trimester and persisted at the 3rd trimester. Similar clinical symptoms (weight loss, nausea, vomiting) were also reported during the first trimester of her first pregnancy and the first pregnancy of her mother. Results DNA sequencing of the hTSHR gene of this woman and her mother identifies a heterozygous variant changing valine to isoleucine residue at codon 597 in the transmembrane domain (TMD) of this receptor. In vitro functional studies of this variant showed increased constitutive activity in regard to the basal level of cAMP and IP3 production and to the low cell-surface expression, while response to TSH was reduced compared to that of the wild-type receptor. The Val597Ile variant presented a dose-dependent increase in cAMP response to hGC and human luteinizing hormone (hLH). Simulation of the protein dynamics showed a high structural impact of the Val597Ile variant on helices 3 (TMH3) and 5 (TMH5) of the transmembrane domain participating to constitutive activity and hCG sensitivity. Conclusion We describe a new variant in the transmembrane region of the hTSHR gene with increased constitutive activity and hCG hypersensitivity in familial gestational hyperthyroidism.Aims Despite three decades of study, it is still challenging to discriminate acute apical variant stress cardiomyopathy (AVSCM) from acute left anterior descending-myocardial infarction (LAD-MI) at the time of presentation. A biomarker or practical imaging modality that can differentiate these two entities is highly desirable. Our objective was to characterize left ventricular (LV) mechanical deformation using 2-dimensional (2D) echocardiographic strain imaging in an attempt to discriminate AVSCM from LAD-MI at presentation. Methods and results We studied 108 women (60 AVSCM, 48 ST segment elevation LAD-MI). All underwent echocardiography within 48 hours of presentation. Sulfatinib chemical structure 2D longitudinal strain (LS) from an 18-segment LV model was performed, with global LS (GLS) taken as the average of all 18 segments. GLS was abnormal, but did not differentiate AVSCM from LAD-MI. Mean LS of the basal and mid-anterior, basal, and mid-anteroseptum segments were significantly lower in LAD-MI vs AVSCM group (-14 ± 9% vs -20 ± 8%; -11 ± 7% vs -14 ± 6%; -9 ± 8% vs -14 ± 8%; -9 ± 7% vs -13 ± 5%, respectively, all P ≤ .05). Mean LS of the basal inferior and inferolateral segments was significantly higher in the LAD-MI vs. AVSCM group (-19 ± 9% vs -13 ± 7%; -23 ± 11% vs -18 ± 7%, respectively, all P ≤ .05). Using ROC curve analysis, segmental strain ratio of average basal inferior and inferolateral segments LS to average mid- and basal anterior and anteroseptum segments LS of ≥1.58 was 90% specific for LAD-MI [area under the curve (AUC) 0.87; P less then .001]. Conclusion Longitudinal strain patterns are useful in discriminating AVSCM from LAD-MI patients at presentation and may be valuable in stratifying patients for invasive evaluation.Vaccine development against SARS-CoV-2 has drawn attention around the globe due to the exploding pandemic. Although COVID-19 is caused by a new coronavirus, SARS-CoV-2, previous research on other coronavirus vaccines, such as FIPV, SARS and MERS, has provided valuable information for the rapid development of COVID-19 vaccine. However, important knowledge gaps remain – some are specific to SARS-CoV-2, others are fundamental to immunology and vaccinology. Here we discuss areas that need to be addressed for COVID-19 vaccine development, and what can be learned from examples of vaccine development in the past. Since the beginning of the outbreak, the research progress on COVID-19 has been remarkable. We are therefore optimistic about the rapid development of COVID-19 vaccine. This article is protected by copyright. All rights reserved.The SARS‐Cov‐2 (COVID‐19) pandemic has already claimed over 200,000 lives. Quite early on in this pandemic, it was recognised that the virus triggers the immune system leading to a cytokine storm in some severely ill patients [1]. This hyper‐responsiveness has been suggested to be the predominant aetiology for clinical deterioration and mortality in patients with this infection [2]. More recently, there have been several reports of increased thrombotic events in these patients [3‐6]. From a laboratory perspective, this hypercoagulability is reflected in the marked elevation of the fibrinolytic marker, D‐dimer, in almost all hospitalised COVID‐19 patients [7]. We must, therefore, ask ourselves what is the link between the extremes of the immune system, presenting as cytokine storm, and the extremes of coagulation, presenting as arterial and venous thromboembolism?The Medtronic Autologs System allows real-time clinician review of HeartWare™ HVAD™ System logfiles, providing supplemental pump data to aid in patient management. In its first year of availability, Autologs generated a 70% increase in logfile submissions, with 73% of all logfile requests being sent to Autologs. Within a month of its launch, Autologs submissions outnumbered the amount of logfiles submitted for manual review. Following the v1.1 release, there was a 20% increase in logfile submissions, with 77% of all logfile requests being Autologs. With the introduction of v1.2, there was another 35% increase in logfile submissions, with nearly 90% of all logfile requests being Autologs. The widespread adoption and utility of the Autologs System highlights the need for clinician access to real-time data analysis in the field of Mechanical Circulatory Support.