Acute Kidney Injury Biomarkers: from bench to clinical use

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Complex Incremental Sheet Forming Using Back Die Support on Aluminium 2024, 5083 and 7075 alloys

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Heart failure with reduced ejection fraction polypill implementation strategy in India: A convergent parallel mixed methods study

INTRODUCTION: A polypill-based implementation strategy has been proposed to increase rates of guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction. This has the potential to improve mortality and morbidity in India and undertreated populations globally. METHODS: We conducted a convergent parallel mixed methods study integrating quantitative data from stakeholder surveys using modified implementation science outcome measures and qualitative data from key informant in-depth interviews. Our objective was to explore physician, nurse, pharmacist, and patient perspectives on a HFrEF polypill implementation strategy in India from January 2021 to April 2021. Quantitative and qualitative data were integrated to develop an Implementation Research Logic Model. RESULTS: Among 69 respondents to the stakeholder survey, there was moderate acceptability (mean [SD] 3.8 [1.0]), appropriateness (3.6 [1.0]), and feasibility (3.7 [1.0]) of HFrEF polypill implementation strategy. Participants in the key-informant in-depth interviews (n = 20) highlighted numerous relative advantages of the HFrEF polypill innovation including potential to simplify medication regimens and improve patient adherence. Key relative disadvantages elucidated, include concerns about side effects and interruption of multiple GDMT medications due to polypill discontinuation for side effects or hospitalizations. Based on this data, the proposed implementation strategies in the Implementation Research Logic Model include 1) HFrEF polypills, 2) HFrEF polypill initiation, titration, and maintenance protocols, and 3) HFrEF polypill laboratory monitoring protocols for safety which we postulate will lead to desired clinical and implementation outcomes through multiple mechanisms including increased medication adherence to a single pill. CONCLUSION: This study demonstrates that a HFrEF polypill-based implementation strategy is considered acceptable, feasible, and appropriate among healthcare providers in India. We identified contextually relevant determinants, strategies, mechanism, and outcomes outlined in an Implementation Research Logic Model to inform future research to improve heart failure care in South Asia

An unusual congregation of organisms in the catches off Kovalam, Madras

The fishermen belonging to Kovalam had a hectic activity in harvesting huge quantities of fish from the Kovalam bay from 26-8-'87 to 4-9-'87. Fishermen employed all available gears for catching the fish and prawns. According to them, this was due to the appearance of 'Vandal thanneer' or turbid water close to the shore. The present account embodies the results of the observations made on this unusual phenomenon

Neutrophil gelatinase-associated lipocalin in dehydrated patients: a preliminary report

<p>Abstract</p> <p>Background</p> <p>Acute kidney injury has been recognized as a major contributor to end stage renal disease. Although neutrophil gelatinase-associated lipocalin (Ngal) has been reported as a promising biomarker for early detection of acute kidney injury, no study has yet examined its potential clinical impact in patients with normal renal function. The purpose of current study is to investigate possible difference in serum Ngal levels between dehydrated and control patients.</p> <p>Findings</p> <p>A total of twelve patients presented with symptoms of mild dehydration defined by history of diarrheas or vomiting and orthostatic (postural) hypotension and an age and sex matched group of twelve control patients were included. The two groups of patients did not seem to differ in basic clinical and laboratory parameters. Serum Ngal was higher in dehydrated patients when compared to control group (Ngal = 129.4 ± 25.7 ng/mL vs 60.6 ± 0.4 ng/mL, p = 0.02). Ngal was not correlated with age, hemoglobin, white blood cell count, red blood cell count, urea or creatinine.</p> <p>Conclusions</p> <p>The presence of elevated Ngal levels in dehydrated patients may suggest its role as a very sensitive biomarker in even minimal and "silent" prerenal kidney dysfunction</p

Urinary nitrate might be an early biomarker for pediatric acute kidney injury in the emergency department

NO is involved in normal kidney function and perturbed in acute kidney injury (AKI). We hypothesized that urinary concentration of NO metabolites, nitrite, and nitrate would be lower in children with early AKI presenting to the emergency department (ED), when serum creatinine (SCr) was uninformative. Patients up to 19 y were recruited if they had a urinalysis and SCr obtained for routine care. Primary outcome, AKI, was defined by pediatric Risk, Injury, Failure, Loss of function, End-stage renal disease (pRIFLE) criteria. Urinary nitrite and nitrate were determined by HPLC. A total of 252 patients were enrolled, the majority (93%) of whom were without AKI. Although 18 (7%) had AKI by pRIFLE, 50% may not have had it identified by the SCr value alone at the time of visit. Median urinary nitrate was lower for injury versus risk (p = 0.03); this difference remained significant when the injury group was compared against the combined risk and no AKI groups (p = 0.01). Urinary nitrite was not significantly different between groups. Thus, low urinary nitrate is associated with AKI in the pediatric ED even when SCr is normal. Predictive potential of this putative urinary biomarker for AKI needs further evaluation in sicker patients

Simultaneous non-negative matrix factorization for multiple large scale gene expression datasets in toxicology

Non-negative matrix factorization is a useful tool for reducing the dimension of large datasets. This work considers simultaneous non-negative matrix factorization of multiple sources of data. In particular, we perform the first study that involves more than two datasets. We discuss the algorithmic issues required to convert the approach into a practical computational tool and apply the technique to new gene expression data quantifying the molecular changes in four tissue types due to different dosages of an experimental panPPAR agonist in mouse. This study is of interest in toxicology because, whilst PPARs form potential therapeutic targets for diabetes, it is known that they can induce serious side-effects. Our results show that the practical simultaneous non-negative matrix factorization developed here can add value to the data analysis. In particular, we find that factorizing the data as a single object allows us to distinguish between the four tissue types, but does not correctly reproduce the known dosage level groups. Applying our new approach, which treats the four tissue types as providing distinct, but related, datasets, we find that the dosage level groups are respected. The new algorithm then provides separate gene list orderings that can be studied for each tissue type, and compared with the ordering arising from the single factorization. We find that many of our conclusions can be corroborated with known biological behaviour, and others offer new insights into the toxicological effects. Overall, the algorithm shows promise for early detection of toxicity in the drug discovery process

Development of a novel renal activity index of lupus nephritis in children & young adults

BACKGROUND: Noninvasive estimation of the degree of inflammation seen on kidney biopsy with lupus nephritis (LN) remains difficult. The objective of this study was to develop a Renal Activity Index for Lupus (RAIL) that, based solely on laboratory measures, accurately reflects histological LN activity. METHODS: We assayed traditional LN laboratory tests and 16 urine biomarkers (UBMs) in children (n=47) at the time of kidney biopsy. Histological LN activity was measured by the NIH Activity Index (NIH-AI) and the Tubulointerstitial Activity Index (TIAI). High LN-activity status (vs. moderate/low) was defined as NIH-AI scores \u3e 10 (vs.5 (vs.92% accuracy and LN-activityTIAI status with \u3e80% accuracy. RAIL accuracy was minimally influenced by concomitant LN damage. Accuracies between 71 and 85% were achieved without standardization of the UBMs. The strength of these UBMs to reflect LN-activity status was confirmed by principal component and linear discriminant analyses. CONCLUSION: The RAIL is a robust and highly accurate noninvasive measure of LN-activity. The measurement properties of the RAIL, which reflect the degree of inflammatory changes as seen on kidney biopsy, will require independent validation. This article is protected by copyright. All rights reserved

Chronic Inflammation in Chronic Kidney Disease Progression: Role of Nrf2

Despite recent advances in the management of chronic kidney disease (CKD), morbidity and mortality rates in these patients remain high. Although pressure-mediated injury is a well-recognized mechanism of disease progression in CKD, emerging data indicate that an intermediate phenotype involving chronic inflammation, oxidative stress, hypoxia, senescence, and mitochondrial dysfunction plays a key role in the etiology, progression, and pathophysiology of CKD. A variety of factors promote chronic inflammation in CKD, including oxidative stress and the adoption of a proinflammatory phenotype by resident kidney cells. Regulation of proinflammatory and anti-inflammatory factors through NF-κB– and nuclear factor, erythroid 2 like 2 (Nrf2)–mediated gene transcription, respectively, plays a critical role in the glomerular and tubular cell response to kidney injury. Chronic inflammation contributes to the decline in glomerular filtration rate (GFR) in CKD. Whereas the role of chronic inflammation in diabetic kidney disease (DKD) has been well-elucidated, there is now substantial evidence indicating unresolved inflammatory processes lead to fibrosis and eventual end-stage kidney disease (ESKD) in several other diseases, such as Alport syndrome, autosomal-dominant polycystic kidney disease (ADPKD), IgA nephropathy (IgAN), and focal segmental glomerulosclerosis (FSGS). In this review, we aim to clarify the mechanisms of chronic inflammation in the pathophysiology and disease progression across the spectrum of kidney diseases, with a focus on Nrf2