The UK death toll from COVID-19 is currently the fourth worst in the world behind the USA, Brazil and Mexico. Possible reasons include delays in lockdown, the provision of scientific advice to government and the decisions that government made based on the information they were given. When we review our performance and plan for the next public health crisis, we need to be brave enough to dare to challenge the NHS and its advisors.The increasing incidence of infective endocarditis in England is real, and education is critical to ensure swift diagnosis and best clinical outcomes. Factors responsible remain speculative, but multiple explanations are likely.This year marks the 100th anniversary of the death of General William Crawford Gorgas, probably the most famous public health administrator, who first achieved fame for his work in dealing with the epidemic of yellow fever in Cuba in the early 20th century.Coronary artery disease and its associated clinical sequelae are a significant medical burden to clinicians and patients. Severe coronary artery disease presenting in the context of acute myocardial ischaemia, or stable plaques causing chronic symptoms despite best conservative and pharmacological intervention, are often amenable to further intervention such as coronary artery bypass grafting. This procedure has been extensively compared to newer and less invasive techniques, such as percutaneous coronary intervention, and other minimally invasive procedures such as robotic or endoscopic techniques. This review summarises the current evidence on revascularisation of the left coronary artery system, with particular emphasis on key clinical endpoints of mortality, myocardial infarction, stroke and repeat revascularisation.The practice of regional anaesthesia has advanced rapidly, with well-defined benefits such as reducing pain, reduced opioid consumption, and improved quality of early recovery. Challenges include extending the benefit beyond the immediate postoperative period, improving access for patients and defining the long-term effects.Implantable cardiac defibrillators are a key component in preventing sudden cardiac death for patients with life-threatening arrhythmias. Through ageing, frailty and the progression of cardiac and non-cardiac morbidity, many will develop a 'life-limiting' condition. This raises the challenge of how to approach making decisions to deactivate the defibrillator function. This article discusses the background to deactivation of implantable cardioverter defibrillators and the practical considerations for different circumstances.The COVID-19 pandemic has predominantly affected the adult population. The disease is less well-defined in children (≤18 years). This review summarises the current understanding of the epidemiology, clinical manifestations, and management of COVID-19 in children and adolescents. The prevalence of COVID-19 is significantly lower in children than adults, but paediatric disease is likely underdiagnosed as a result of the high numbers of asymptomatic or mild cases. https://www.selleckchem.com/products/ms177.html Children are vulnerable to family cluster outbreaks, but are unlikely to be index cases within a household. Vertical transmission or breast milk transmission are yet to be proven. Between 10 and 90% of paediatric COVID-19 cases are asymptomatic. Symptomatic cases typically present with mild symptoms, including cough, fever and sore throat. Intensive care admission and mortality are rare. Paediatric multisystem inflammatory syndrome temporally associated with COVID-19 is a rare, but severe, newly emerging phenotype. At present, there is no specific treatment for COVID-19 in adults or children; management is usually supportive. For severe or critical disease, including paediatric multisystem inflammatory syndrome temporally associated with COVID-19, the decision to start antiviral or immunomodulatory therapy should be on a case-by-case basis; in the UK, this should be done within a clinical trial. Further research is needed into both the disease course and treatment of paediatric COVID-19.The National Confidential Enquiry into Patient Outcome and Death undertook a detailed analysis of data from 1269 patients aged 11-25 years, admitted to hospital with intentional injury, affective disorder, or eating disorders, to assess the quality of physical and mental healthcare provided. This article summarises the findings and associated recommendations relevant for the general hospital setting.Lymphoedema is the accumulation of protein-rich interstitial fluid within subcutaneous tissue and skin as a result of dysfunction of the lymphatic system. It is an underestimated, widely neglected and debilitating chronic condition. This article presents an overview of lymphoedema and recent advances in its management.Playing video games (online or offline) is not a recent phenomenon and for most people it is a leisure activity with no adverse consequences whatsoever. However, for a small minority, gaming has the potential (akin to substance use) to lead on to problematic gaming and gaming disorder. Gaming disorder is a new entry in both the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases. Given gaming's ever-growing popularity, GPs, psychiatrists and other doctors will be increasingly likely to come across individuals who present with gaming-related problems. Consequently, this article gives doctors a basic understanding of what gaming disorder is, its presentations in practice and diagnosis, and its treatment.Intercellular communication is critical for organismal homeostasis, and defects can contribute to human disease states. Polarized epithelial cells execute distinct signaling agendas via apical and basolateral surfaces to communicate with different cell types. Small extracellular vesicles (sEVs), including exosomes and small microvesicles, represent an understudied form of intercellular communication in polarized cells. Human cholangiocytes, epithelial cells lining bile ducts, were cultured as polarized epithelia in a Transwell system as a model with which to study polarized sEV communication. Characterization of isolated apically and basolaterally released EVs revealed enrichment in sEVs. However, differences in apical and basolateral sEV composition and numbers were observed. Genetic or pharmacological perturbation of cellular machinery involved in the biogenesis of intralumenal vesicles at endosomes (the source of exosomes) revealed general and domain-specific effects on sEV biogenesis/release. Additionally, analyses of signaling revealed distinct profiles of activation depending on sEV population, target cell, and the function of the endosomal sorting complex required for transport (ESCRT)-associated factor ALG-2-interacting protein X (ALIX) within the donor cells.