Plasma renin and aldosterone in patients with hypertension before treatment

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Plasma renin activity and aldosterone level in patients with essential hypertension

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Elucidating the aetiology of human Campylobacter coli infections

Peer reviewedPublisher PD

Lipid profile of the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort

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Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice

The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN-γ production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic

Advances in paediatric urology

© 2017 Elsevier Ltd Paediatric urological surgery is often required for managing congenital and acquired disorders of the genitourinary system. In this Series paper, we highlight advances in the surgical management of six paediatric urological disorders. The management of vesicoureteral reflux is evolving, with advocacy ranging from a less interventional assessment and antimicrobial prophylaxis to surgery including endoscopic injection of a bulking agent and minimally invasive ureteric reimplantation. Evidence supports early orchidopexy to improve fertility and reduce malignancy in boys with undescended testes. A variety of surgical techniques have been developed for hypospadias, with excellent outcomes for distal but not proximal hypospadias. Pelvi-ureteric junction obstruction is mostly detected prenatally; indications for surgery have been refined with evidence, and minimally invasive pyeloplasty is now standard. The outlook for patients with neurogenic bladder has been transformed by a combination of clean intermittent catheterisation, algorithms of diagnostic investigations, and innovative medical and surgical therapies. Posterior urethral valves are associated with considerable mortality; fetal diagnosis allows stratification of candidates for intervention, but ongoing bladder dysfunction in patients after valve ablation remains a cause of long-term morbidity

Enhancement of outflow facility in the murine eye by targeting selected tight-junctions of Schlemm's canal endothelia

The juxtacanalicular connective tissue of the trabecular meshwork together with inner wall endothelium of Schlemm’s canal (SC) provide the bulk of resistance to aqueous outflow from the anterior chamber. Endothelial cells lining SC elaborate tight junctions (TJs), down-regulation of which may widen paracellular spaces between cells, allowing greater fluid outflow. We observed significant increase in paracellular permeability following siRNA-mediated suppression of TJ transcripts, claudin-11, zonula-occludens-1 (ZO-1) and tricellulin in human SC endothelial monolayers. In mice claudin-11 was not detected, but intracameral injection of siRNAs targeting ZO-1 and tricellulin increased outflow facility significantly. Structural qualitative and quantitative analysis of SC inner wall by transmission electron microscopy revealed significantly more open clefts between endothelial cells treated with targeting, as opposed to non-targeting siRNA. These data substantiate the concept that the continuity of SC endothelium is an important determinant of outflow resistance, and suggest that SC endothelial TJs represent a specific target for enhancement of aqueous movement through the conventional outflow system

Patient-centric trials for therapeutic development in precision oncology

An enhanced understanding of the molecular pathology of disease gained from genomic studies is facilitating the development of treatments that target discrete molecular subclasses of tumours. Considerable associated challenges include how to advance and implement targeted drug-development strategies. Precision medicine centres on delivering the most appropriate therapy to a patient on the basis of clinical and molecular features of their disease. The development of therapeutic agents that target molecular mechanisms is driving innovation in clinical-trial strategies. Although progress has been made, modifications to existing core paradigms in oncology drug development will be required to realize fully the promise of precision medicine

Lipid profile of the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort

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Follow up of the Hong Kong Cardiovascular Risk Factor Prevalence Survey cohort

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