International validation of a urinary biomarker panel for identification of active lupus nephritis in children.

Conventional markers of juvenile-onset systemic lupus erythematosus (JSLE) disease activity fail to adequately identify lupus nephritis (LN). While individual novel urine biomarkers are good at detecting LN flares, biomarker panels may improve diagnostic accuracy. The aim of this study was to assess the performance of a biomarker panel to identify active LN in two international JSLE cohorts.Novel urinary biomarkers, namely vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1), lipocalin-like prostaglandin D synthase (LPGDS), transferrin (TF), ceruloplasmin, alpha-1-acid glycoprotein (AGP) and neutrophil gelatinase-associated lipocalin (NGAL), were quantified in a cross-sectional study that included participants of the UK JSLE Cohort Study (Cohort 1) and validated within the Einstein Lupus Cohort (Cohort 2). Binary logistic regression modelling and receiver operating characteristic curve analysis [area under the curve (AUC)] were used to identify and assess combinations of biomarkers for diagnostic accuracy.A total of 91 JSLE patients were recruited across both cohorts, of whom 31 (34 %) had active LN and 60 (66 %) had no LN. Urinary AGP, ceruloplasmin, VCAM-1, MCP-1 and LPGDS levels were significantly higher in those patients with active LN than in non-LN patients [all corrected p values (p c) < 0.05] across both cohorts. Urinary TF also differed between patient groups in Cohort 2 (p c = 0.001). Within Cohort 1, the optimal biomarker panel included AGP, ceruloplasmin, LPGDS and TF (AUC 0.920 for active LN identification). These results were validated in Cohort 2, with the same markers resulting in the optimal urine biomarker panel (AUC 0.991).In two international JSLE cohorts, urinary AGP, ceruloplasmin, LPGDS and TF demonstrate an 'excellent' ability for accurately identifying active LN in children

SGLT2 Inhibitors: Slowing of Chronic Kidney Disease Progression in Type 2 Diabetes

Diabetic kidney disease (DKD) is a topic of increasing concern among clinicians involved in the management of type 2 diabetes mellitus (T2DM). It is a progressive and costly complication associated with increased risk of adverse cardiovascular (CV) and renal outcomes and mortality. Ongoing monitoring of the estimated glomerular filtration (eGFR) rate alongside the urine albumin:creatinine ratio (ACR) is recommended during regular T2DM reviews to enable a prompt DKD diagnosis or to assess disease progression, providing an understanding of adverse risk for each individual. Many people with DKD will progress to end-stage kidney disease (ESKD), requiring renal replacement therapy (RRT), typically haemodialysis or kidney transplantation. A range of lifestyle and pharmacological interventions is recommended to help lower CV risk, slow the advancement of DKD and prevent or delay the need for RRT. Emerging evidence concerning sodium-glucose co-transporter-2 inhibitor (SGLT2i) agents suggests a role for these medicines in slowing eGFR decline, enabling regression of albuminuria and reducing progression to ESKD. Improvements in renal end points observed in SGLT2i CV outcome trials (CVOTs) highlighted the possible impact of these agents in the management of DKD. Data from the canagliflozin CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) have since demonstrated the effectiveness of this medicine in reducing the risk of kidney failure and CV events in a population comprising individuals with T2DM and renal disease. CREDENCE was the first SGLT2i study to examine renal outcomes as the primary end point. Real-world studies have reaffirmed these outcomes in routine clinical practice. This article summarises the evidence regarding the use of SGLT2i medicines in slowing the progression of DKD and examines the possible mechanisms underpinning the renoprotective effects of these agents. The relevant national and international guidance for monitoring and treatment of DKD is also highlighted to help clinicians working to support this vulnerable group

Dexamethasone therapy in COVID-19 patients:implications and guidance for the management of blood glucose in people with and without diabetes

The RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial found that dexamethasone 6 mg once per day for 10 days reduced deaths by one-third in ventilated patients and by one-fifth in other patients, receiving oxygen therapy. This equates to the prevention of one death in around eight ventilated patients, or one in around 25 patients requiring oxygen

Comparing trawl and creel fishing for Norway lobster (Nephrops norvegicus): biological and economic considerations

This study compares the fishing activity and landings of the trawl and creel fisheries for Norway lobster (Nephrops norvegicus (L.)) off the Portuguese coast, and evaluates the financial viability of two vessels typical of each fleet. Crustacean trawlers are part of an industrial fleet that, besides Nephrops, targets deep water shrimps. Creels are used by a multi-gear, multi-target artisanal fleet, fishing only in areas unavailable to trawlers and, when catching Nephrops, set specifically to target this species. Trawlers have in recent years contributed with 85% of the landings in weight, but only 74% in value (2005-2009 average). Despite smaller landings, the Nephrops creel fishery provides individuals of larger size and in better condition, thereby obtaining higher unit prices. Economic viability was also higher for the creel vessel, with trawling being only viable if major costs (such as labor and fuel) are covered by the revenue from other target species (e. g., the rose shrimp). At present, Nephrops populations on the South and SW coast are subject to intense fishing and to a recovery plan. The possibility of reallocation of some of the fishing effort directed at Nephrops from trawlers to creels is discussed in terms of the conservation of the resource and economic return.Foundation for Science and Technology, Portugal: Project "Nephrops survival when escaping from trawls nets and by-catch escaping devices" [PDCT/MAR/59366/2004]; Foundation for Science and Technology, Portugal: Project "Environmental impact of fixing gears in the southwest coast of Portugal. Combine fisheries and marine ecosystem conservation" [POCTI/CTA/49248/2002]info:eu-repo/semantics/publishedVersio

The Place and Value of Sodium-Glucose Cotransporter 2 Inhibitors in the Evolving Treatment Paradigm for Type 2 Diabetes Mellitus: A Narrative Review

Over recent years, the expanding evidence base for sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapies has revealed benefits beyond their glucose-lowering efficacy in the treatment of Type 2 diabetes mellitus (T2DM), resulting in their recognition as cardiorenal medicines. While SGLT2is continue to be recommended among the second-line therapies for the treatment of hyperglycaemia, their true value now extends to the prevention of debilitating and costly cardiovascular and renal events for high-risk individuals, with particular benefit shown in reducing major adverse cardiac events and heart failure (HF) and slowing the progression of chronic kidney disease. However, SGLT2i usage is still suboptimal among groups considered to be at greatest risk of cardiorenal complications. The ongoing coronavirus disease 2019 (COVID-19) pandemic has intensified financial pressures on healthcare systems, which may hamper further investment in newer effective medicines. Emerging evidence indicates that glycaemic control should be prioritised for people with T2DM in the era of COVID-19 and practical advice on the use of T2DM medications during periods of acute illness remains important, particularly for healthcare professionals working in primary care who face multiple competing priorities. This article provides the latest update from the Improving Diabetes Steering Committee, including perspectives on the value of SGLT2is as cost-effective therapies within the T2DM treatment paradigm, with particular focus on the latest published evidence relating to the prevention or slowing of cardiorenal complications. The implications for ongoing and future approaches to diabetes care are considered in the light of the continuing coronavirus pandemic, and relevant aspects of international treatment guidelines are highlighted with practical advice on the appropriate use of SGLT2is in commonly occurring T2DM clinical scenarios. The ‘SGLT2i Prescribing Tool for T2DM Management’, previously published by the Steering Committee, has been updated to reflect the latest evidence and is provided in the Supplementary Materials to help support clinicians delivering T2DM care

Naturally Occurring Variants of Human Α9 Nicotinic Receptor Differentially Affect Bronchial Cell Proliferation and Transformation

Isolation of polyadenilated mRNA from human immortalized bronchial epithelial cell line BEP2D revealed the presence of multiple isoforms of RNA coded by the CHRNA9 gene for α9 nicotinic acetylcholine receptor (nAChR). BEP2D cells were homozygous for the rs10009228 polymorphism encoding for N442S amino acid substitution, and also contained mRNA coding for several truncated isoforms of α9 protein. To elucidate the biologic significance of the naturally occurring variants of α9 nAChR, we compared the biologic effects of overexpression of full-length α9 N442 and S442 proteins, and the truncated α9 variant occurring due to a loss of the exon 4 sequence that causes frame shift and early termination of the translation. These as well as control vector were overexpressed in the BEP2D cells that were used in the assays of proliferation rate, spontaneous vs. tobacco nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced cellular transformation, and tumorigenicity in cell culture and mice. Overexpression of the S442 variant significantly increased cellular proliferation, and spontaneous and NNK-induced transformation. The N442 variant significantly decreased cellular transformation, without affecting proliferation rate. Overexpression of the truncated α9 significantly decreased proliferation and suppressed cellular transformation. These results suggested that α9 nAChR plays important roles in regulation of bronchial cell growth by endogenous acetylcholine and exogenous nicotine, and susceptibility to NNK-induced carcinogenic transformation. The biologic activities of α9 nAChR may be regulated at the splicing level, and genetic polymorphisms in CHRNA9 affecting protein levels, amino acid sequence and RNA splicing may influence the risk for lung cancer

Resistance through realism : Youth subculture films in 1970s (and 1980s) Britain

This document is the Accepted Manuscript version of the following article: Nathaniel Weiner, ‘Resistance through realism: Youth subculture films in 1970s (and 1980s) Britain’. The final, definitive version of this paper has been published in European Journal of Cultural Studies, November 2015, DOI: https://doi.org/10.1177/1367549415603376. Published by SAGE Publishing.Film scholars have argued that the British social realist films of the late 1950s and early 1960s reflect the concerns articulated by British cultural studies during the same period. This article looks at how the social realist films of the 1970s and early 1980s similarly reflect the concerns of British cultural studies scholarship produced by the University of Birmingham’s Centre for Contemporary Cultural Studies during the 1970s. It argues that the Centre for Contemporary Cultural Studies’ approach to stylised working-class youth subcultures is echoed in the portrayal of youth subcultures in the social realist films Pressure (1976), Bloody Kids (1979), Babylon (1980) and Made in Britain (1982). This article explores the ways in which these films show us both the strengths and weaknesses of the Centre for Contemporary Cultural Studies’ work on subcultures.Peer reviewe