Tissue factor levels in type 2 diabetes mellitus

INTRODUCTION : Type 2 diabetes mellitus is a pandemic associated with disturbance inhaemostasis that could contribute to the development of diabetic vascular disease and accelerated atherosclerosis. In this population, hypercoagulation is prevalent, as well as pathological changes to erythrocytes. This is mainly due to upregulated circulating inflammatory markers. MATERIALS AND METHODS : Here we looked at tissue factor (TF) levels using ELISA, in a sample of diabetics, with and without cardiovascular complications. Diabetic subjects were recruited from the diabetic clinic at Steve Biko Academic Hospital, Pretoria, South Africa. 20 diabetics with cardiovascular disease and 22 without were enrolled to participate. RESULTS AND CONCLUSION : TF levels were significantly elevated in both diabetic groups when compared to the controls. We suggest that pathologic plasma TF activity, as marker of increased propensity of clot pathology, should be investigated. Agents that might lower TF levels might also possibly lower thrombotic complications.This work is based on the research supported in part by the National Research Foundation of South Africa (UNIQUE GRANT NO: 92709) and the MRC : E Pretorius (fund number A0X331).http://link.springer.com/journal/112018-05-28hb2017Physiolog

Serum metabolome changes in relation to prothrombotic state induced by combined oral contraceptives with drospirenone and ethinylestradiol

The association between hypercoagulability and use of drospirenone (DRSP) and ethinylestradiol (EE) containing combined oral contraceptives (COCs) is an important clinical concern. We have previously reported that the two formulations of DRSP combined with EE (namely, DRSP/20EE and DRSP/30EE) bring about a prothrombotic state in hemostatic traits of female users. We report here the serum metabolomic changes in the same study cohort in relation to the attendant prothrombotic state induced by COC use, thus offering new insights on the underlying biochemical mechanisms contributing to the altered coagulatory profile with COC use. A total of 78 healthy women participated in this study and were grouped as follows: control group not using oral contraceptives (n = 25), DRSP/20EE group (n = 27), and DRSP/30EE group (n = 26). Untargeted metabolomics revealed changes in amino acid concentrations, particularly a decrease in glycine and an increase in both cysteine and lanthionine in the serum, accompanied by variations in oxidative stress markers in the COC users compared with the controls. Of importance, this study is the first to link specific amino acid variations, serum metabolites, and the oxidative metabolic profile with DRSP/EE use. These molecular changes could be linked to specific biophysical coagulatory alterations observed in the same individuals. These new findings lend evidence on the metabolomic substrates of the prothrombotic state associated with COC use in women and informs future personalized/precision medicine research. Moreover, we underscore the importance of an interdisciplinary approach to evaluate venous thrombotic risk associated with COC use.The National Research Foundation (NRF) (South Africa)https://home.liebertpub.com/publications/omics-a-journal-of-integrative-biology/432021-07-01am2021AnatomyPhysiolog

A global cline in a colour polymorphism suggests a limited contribution of gene flow towards the recovery of a heavily exploited marine mammal

Evaluating how populations are connected by migration is important for understanding species resilience because gene flow can facilitate recovery from demographic declines. We therefore investigated the extent to which migration may have contributed to the global recovery of the Antarctic fur seal (Arctocephalus gazella), a circumpolar distributed marine mammal that was brought to the brink of extinction by the sealing industry in the eighteenth and nineteenth centuries. It is widely believed that animals emigrating from South Georgia, where a relict population escaped sealing, contributed to the re-establishment of formerly occupied breeding colonies across the geographical range of the species. To investigate this, we interrogated a genetic polymorphism (S291F) in the melanocortin 1 receptor gene, which is responsible for a cream-coloured phenotype that is relatively abundant at South Georgia and which appears to have recently spread to localities as far afield as Marion Island in the sub-Antarctic Indian Ocean. By sequencing a short region of this gene in 1492 pups from eight breeding colonies, we showed that S291F frequency rapidly declines with increasing geographical distance from South Georgia, consistent with locally restricted gene flow from South Georgia mainly to the South Shetland Islands and Bouvetøya. The S291F allele was not detected farther afield, suggesting that although emigrants from South Georgia may have been locally important, they are unlikely to have played a major role in the recovery of geographically more distant populations

A global cline in a colour polymorphism suggests a limited contribution of gene flow towards the recovery of a heavily exploited marine mammal

Evaluating how populations are connected by migration is important for understanding species resilience because gene flow can facilitate recovery from demographic declines. We therefore investigated the extent to which migration may have contributed to the global recovery of the Antarctic fur seal (Arctocephalus gazella), a circumpolar distributed marine mammal that was brought to the brink of extinction by the sealing industry in the eighteenth and nineteenth centuries. It is widely believed that animals emigrating from South Georgia, where a relict population escaped sealing, contributed to the re-establishment of formerly occupied breeding colonies across the geographical range of the species. To investigate this, we interrogated a genetic polymorphism (S291F) in the melanocortin 1 receptor gene, which is responsible for a cream-coloured phenotype that is relatively abundant at South Georgia and which appears to have recently spread to localities as far afield as Marion Island in the sub-Antarctic Indian Ocean. By sequencing a short region of this gene in 1492 pups from eight breeding colonies, we showed that S291F frequency rapidly declines with increasing geographical distance from South Georgia, consistent with locally restricted gene flow from South Georgia mainly to the South Shetland Islands and Bouvetøya. The S291F allele was not detected farther afield, suggesting that although emigrants from South Georgia may have been locally important, they are unlikely to have played a major role in the recovery of geographically more distant populations.J.I.H., E.B., A.J.P., E.H., L.M.B., C.K., F.C., N.K., B.F. and A.M. were funded by Deutsche Forschungsgemeinschaft (DFG) standard grant no. (HO 5122/3-1) and this research was also partly funded by the DFG as part of the SFB TRR 212 (NC3, project A01). A.C.C., C.L., K.M.K. and A.L. were funded by projects from the Norwegian Antarctic Research Expeditions. The Department of Science and Technology of South Africa provided funding through the National Research Foundation (NRF) for Marion Island research. Support for the publication fee was provided by the DFG and the Open Access Publication Funds of Bielefeld University.http://rsos.royalsocietypublishing.orgam2019Mammal Research InstituteZoology and Entomolog

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Novel diagnostic and monitoring tools in stroke : an individualized patient-centered precision medicine approach

Central to the pathogenesis of ischaemic stroke are the normally protective processes of platelet adhesion and activation. Experimental evidence has shown that the ligand-receptor interactions in ischaemic stroke represent a thrombo-inflammatory cascade, which presents research opportunities into new treatment. However, as anti-platelet drugs have the potential to cause severe side effects in ischaemic stroke patients (as well as other vascular disease patients), it is important to carefully monitor the risk of bleeding and risk of thrombus in patients receiving treatment. Because thrombo-embolic ischaemic stroke is a major health issue, we suggest that the answer to adequate treatment is based on an individualized patient-centered approach, inline with the latest NIH precision medicine approach. A combination of viscoelastic methodologies may be used in a personalized patient-centered regime, including thromboelastography (TEG®) and the lesser used scanning electron microscopy approach (SEM). Thromboelastography provides a dynamic measure of clot formation, strength, and lysis, whereas SEM is a visual structural tool to study patient fibrin structure in great detail. Therefore, we consider the evidence for TEG® and SEM as unique means to confirm stroke diagnosis, screen at-risk patients, and monitor treatment efficacy. Here we argue that the current approach to stroke treatment needs to be restructured and new innovative thought patterns need to be applied, as even approved therapies require close patient monitoring to determine efficacy, match treatment regimens to each patient's individual needs, and assess the risk of dangerous adverse effects. TEG® and SEM have the potential to be a useful tool and could potentially alter the clinical approach to managing ischaemic stroke. As envisaged in the NIH precision medicine approach, this will involve a number of role players and innovative new research ideas, with benefits that will ultimately only be realized in a few years. Therefore, with this ultimate goal in mind, we suggest that an individualized patient-orientated approach is now available and therefore already within our ability to use.NRF and MRC of South Africa : E Pretoriushttps://www.jstage.jst.go.jp/browse/jatam2016Physiolog

Data from: The genetic legacy of extreme exploitation in a polar vertebrate

Microsatellite data (39 loci) from Antarctic fur seals and Subantarctic fur seals, used in the paper: "The genetic legacy of extreme exploitation in a polar vertebrate" Abstract Understanding the effects of human exploitation on the genetic composition of wild populations is important for predicting species persistence and adaptive potential. We therefore investigated the genetic legacy of large-scale commercial harvesting by reconstructing on a global scale the recent demographic history of the Antarctic fur seal (Arctocephalus gazella), a species that was hunted to the brink of extinction by 18th and 19th century sealers. Molecular genetic data from over 2,000 individuals, sampled from all eight major breeding colonies across the species᾿ circumpolar geographic distribution, show that at least four relict populations around Antarctica survived commercial hunting. Coalescent simulations suggest that all of these populations experienced severe bottlenecks down to effective population sizes of around 150–200. Nevertheless, comparably high levels of neutral genetic variability were retained as these declines are unlikely to have been strong enough to deplete allelic richness by more than around 15%. These findings suggest that even dramatic short-term declines need not necessarily result in major losses of diversity, and explain the apparent contradiction between the high genetic diversity of this species and its extreme exploitation history. Funding This research was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) in the framework of a Sonderforschungsbereich (project numbers 316099922 and 396774617–TRR 212) and the priority programme "Antarctic Research with Comparative Investigations in Arctic Ice Areas" SPP 1158 (project number 424119118). It was also funded by Norwegian Antarctic Research Expeditions (NARE) programme. This work contributes to the Ecosystems project of the British Antarctic Survey, Natural Environmental Research Council, and is part of the Polar Science for Planet Earth Programme. The Department of Environmental Affairs provided logistical support for research at Marion Island and the Department of Science and Technology of South Africa provided funding through the National Research Foundation (NRF). We are grateful to Caroline Bonin, Debbie Baird-Bower and Iain Staniland together with the seal biologists working within the Marion Island Marine Mammal Programme for sample collection and logistics. We acknowledge support for the Article Processing Charge by the Deutsche Forschungsgemeinschaft and the Open Access Publication Fund of Bielefeld University