Managing hyperlipidaemia in patients with COVID-19 and during its pandemic: An expert panel position statement from HEART UK

The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes Coronavirus Disease 2019 (COVID-19) has resulted in a pandemic. SARS-CoV-2 is highly contagious and its severity highly variable. The fatality rate is unpredictable but is amplified by several factors including advancing age, atherosclerotic cardiovascular disease, diabetes mellitus, hypertension and obesity. A large proportion of patients with these conditions are treated with lipid lowering medication and questions regarding the safety of continuing lipid-lowering medication in patients infected with COVID-19 have arisen. Some have suggested they may exacerbate their condition. It is important to consider known interactions with lipid-lowering agents and with specific therapies for COVID-19. This statement aims to collate current evidence surrounding the safety of lipid-lowering medications in patients who have COVID-19. We offer a consensus view based on current knowledge and we rated the strength and level of evidence for these recommendations. Pubmed, Google scholar and Web of Science were searched extensively for articles using search terms: SARS-CoV-2, COVID-19, coronavirus, Lipids, Statin, Fibrates, Ezetimibe, PCSK9 monoclonal antibodies, nicotinic acid, bile acid sequestrants, nutraceuticals, red yeast rice, Omega-3-Fatty acids, Lomitapide, hypercholesterolaemia, dyslipidaemia and Volanesorsen. There is no evidence currently that lipid lowering therapy is unsafe in patients with COVID-19 infection. Lipid-lowering therapy should not be interrupted because of the pandemic or in patients at increased risk of COVID-19 infection. In patients with confirmed COVID-19, care should be taken to avoid drug interactions, between lipid-lowering medications and drugs that may be used to treat COVID-19, especially in patients with abnormalities in liver function tests

Mitotic Arrest in Teratoma Susceptible Fetal Male Germ Cells

Formation of germ cell derived teratomas occurs in mice of the 129/SvJ strain, but not in C57Bl/6 inbred or CD1 outbred mice. Despite this, there have been few comparative studies aimed at determining the similarities and differences between teratoma susceptible and non-susceptible mouse strains. This study examines the entry of fetal germ cells into the male pathway and mitotic arrest in 129T2/SvJ mice. We find that although the entry of fetal germ cells into mitotic arrest is similar between 129T2/SvJ, C57Bl/6 and CD1 mice, there were significant differences in the size and germ cell content of the testis cords in these strains. In 129T2/SvJ mice germ cell mitotic arrest involves upregulation of p27KIP1, p15INK4B, activation of RB, the expression of male germ cell differentiation markers NANOS2, DNMT3L and MILI and repression of the pluripotency network. The germ-line markers DPPA2 and DPPA4 show reciprocal repression and upregulation, respectively, while FGFR3 is substantially enriched in the nucleus of differentiating male germ cells. Further understanding of fetal male germ cell differentiation promises to provide insight into disorders of the testis and germ cell lineage, such as testis tumour formation and infertility

Understanding Eating Disorders in Elite Gymnastics

Eating disorders and disordered eating are more common in high performance sports than the general population, and particularly so in high performance aesthetic sports. This paper presents some of the conceptual difficulties in understanding and diagnosing eating disorders in high performance gymnasts. It presents qualitative and quantitative data from a study designed to ascertain the pattern of eating disorder symptoms, depressive symptoms and levels of self-esteem amongst national and international level gymnasts from the UK in the gymnastic disciplines of sport acrobatics, tumbling and rhythmic gymnastics

Intrinsic factors and the embryonic environment influence the formation of extragonadal teratomas during gestation

Background: Pluripotent cells are present in early embryos until the levels of the pluripotency regulator Oct4 drop at the beginning of somitogenesis. Elevating Oct4 levels in explanted post-pluripotent cells in vitro restores their pluripotency. Cultured pluripotent cells can participate in normal development when introduced into host embryos up to the end of gastrulation. In contrast, pluripotent cells efficiently seed malignant teratocarcinomas in adult animals. In humans, extragonadal teratomas and teratocarcinomas are most frequently found in the sacrococcygeal region of neonates, suggesting that these tumours originate from cells in the posterior of the embryo that either reactivate or fail to switch off their pluripotent status. However, experimental models for the persistence or reactivation of pluripotency during embryonic development are lacking. Methods: We manually injected embryonic stem cells into conceptuses at E9.5 to test whether the presence of pluripotent cells at this stage correlates with teratocarcinoma formation. We then examined the effects of reactivating embryonic Oct4 expression ubiquitously or in combination with Nanog within the primitive streak (PS)/tail bud (TB) using a transgenic mouse line and embryo chimeras carrying a PS/TB-specific heterologous gene expression cassette respectively. Results: Here, we show that pluripotent cells seed teratomas in post-gastrulation embryos. However, at these stages, induced ubiquitous expression of Oct4 does not lead to restoration of pluripotency (indicated by Nanog expression) and tumour formation in utero, but instead causes a severe phenotype in the extending anteroposterior axis. Use of a more restricted T(Bra) promoter transgenic system enabling inducible ectopic expression of Oct4 and Nanog specifically in the posteriorly-located primitive streak (PS) and tail bud (TB) led to similar axial malformations to those induced by Oct4 alone. These cells underwent induction of pluripotency marker expression in Epiblast Stem Cell (EpiSC) explants derived from somitogenesis-stage embryos, but no teratocarcinoma formation was observed in vivo. Conclusions: Our findings show that although pluripotent cells with teratocarcinogenic potential can be produced in vitro by the overexpression of pluripotency regulators in explanted somitogenesis-stage somatic cells, the in vivo induction of these genes does not yield tumours. This suggests a restrictive regulatory role of the embryonic microenvironment in the induction of pluripotency

The hydrologic behaviour of waste rock piles in the Canadian Arctic : snowmelt infiltration and the onset of long term freezing in test piles

This thesis examines the hydrology of three experimental waste rock piles located in the Canadian Arctic at Diavik Diamond Mine (DDMI). Seven years of hydrology data is presented, including measurements of moisture contents, outflow volumes and soil tensions, along with an estimate of annual rainfall infiltration. The hydrology of each pile is influenced by freezing and thawing, and pore water flow is restricted to the time periods when the pile is thawed. The base of each pile contains drain pipes used to collect pore water from the piles, and these pipes are lined with internal heat traces. This research shows that the heat traces significantly influence the thermal behaviour and hydrology of the waste rock. A flooding event in the winter of 2012 interrupted power to the heat trace in two of the waste rock piles, and led to altered outflow volumes and patterns in 2013. A heat trace in the base of the third pile was intentionally turned off in 2011, and led to a significant decrease in the volume of outflow collected from the pile in 2012 and 2013. A bromide tracer was applied to the crest of one of the piles in 2007, and the recovery of the tracer is analysed until 2013. The results of this analysis are used to quantify the average residence time and flow velocity of pore water within the pile. The concentration of stable isotopes is analysed in outflow from the same pile, and is used to estimate the contribution of snowmelt to the total recharge received by the pile. The infiltration of snowmelt into another waste rock pile is estimated using the results of four snow surveys, a snowmelt ablation model, and an infiltration model suitable for use on frozen porous media. The research contained in this thesis provides information that will be incorporated into the final closure plan for DDMI, and will be used to help prevent the formation and release of low quality effluent from the full scale waste rock pile located at the mine site.Science, Faculty ofEarth, Ocean and Atmospheric Sciences, Department ofGraduat

Diabetes and Cardiovascular Disease

ii.168 hal.; ill.; 21 c

Oxford Medical Publications

This book fills an obvious gap in the Handbook series and indeed a major lacuna in the medical literature. Too often investigations of a particular condition are lost in the welter of other text. Alternatively, they appear as specialist books in pathology and radiology. One unique feature of this book is the inclusion of all clinical investigative techniques, i.e. both truly clinical tests in the shape of symptoms and signs and then laboratorybased investigations. This stops what is often an artificial separation. Each section is clearly put together with the intent of easing rapid reference. This is essential if the book is to have (and I believe it does have) real usefulness for bedside medicine. There are many otheruseful aspects of the text. These include a comprehensive list of abbreviations—the bugbear of medicine, as well as reference ranges which some laboratories still do not append to results. Overall, the Handbook should be of benefit to not just clinical students and junior doctors in training, but all who have patient contact. With this in one pocket, and Longmore in the other, there should be little excuse for errors in diagnosis and investigation, with the added benefit that the balance between the two will allow the upright posture to be maintained. Professor Sir George Alberti President of The Royal College of Physicians of London July 2002This book is sold subject to the condition that it shall not, by way of trade or otherwise, be lent, re-sold, hired out, or otherwise circulated without the publisher’s prior consent in any form of binding or cover other than that in which it is published and without a similar condition including this condition being imposed on the subsequent purchaser