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Author(s): Ankur Singh [sup.1] , Jaideep Rajawat [sup.2] , Akanksha Singh [sup.3] , Abhishek Abhinay [sup.3] , Rajniti Prasad [sup.2] , Om Prakash Mishra [sup.3] Author Affiliations: (1) grid.411507.6, 0000 [...]

Background The aims of this study were (1) to detect toll-like receptor (TLR)-3, TLR-4 and CD80 expression in peripheral blood mononuclear cells (PBMCs) and estimate urinary CD80 levels in children with idiopathic nephrotic syndrome and (2) to investigate the utility of these markers to differentiate between biopsy-proven minimal change disease (MCD) and focal segmental glomeruloscelerosis (FSGS). Methods The study included 70 patients with idiopathic nephrotic syndrome (NS), of whom 40 had steroid-sensitive NS (SSNS; 25 with active NS, 15 in remission) and 30 had steroid-resistant NS (SRNS) patients, and 23 healthy controls. TLR-3, TLR- 4 and CD80 mRNA expression levels in PBMCs were determined and the urinary CD80 level estimated. Results Median TLR-3, TLR-4 and CD80 mRNA expression levels were higher in patients with active SSNS than in those with SRNS, and the latter patient group also had significantly lower expression levels than the controls. The expression levels of these markers were associated with reductions in remission. Patients with biopsy-proven MCD had higher median expression levels of these markers than those with FSGS, but the differences were not statistically significant. Median urinary CD80/creatinine values were significantly higher in patients with SSNS and SRNS than in the controls and steroid-sensitive patients in remission (p < 0.001). CD80 levels were also significantly higher in patients with MCD than in those with FSGS (p = 0.002). A cut-off level of >914.5 ng/g had a sensitivity of 86.6%, specificity 71.4% and area under the curve of 0.828 (95% confidence interval 0.678-0.978, p = 0.002) for the diagnosis of MCD. Conclusions Increased expressions of TLR-3, TLR-4 and CD80 mRNA and the level of urinary CD80/creatinine could be useful markers to differentiate patients of SSNS in relapse from those with SRNS. Further these markers can also distinguish biopsy proven MCD from FSGS in SRNS patients., Author(s): Om P. Mishra [sup.1] , Ravindra Kumar [sup.1] , Gopeshwar Narayan [sup.2] , Pradeep Srivastava [sup.3] , Abhishek Abhinay [sup.1] , Rajniti Prasad [sup.1] , Ankur Singh [sup.1] , [...]

Background Urinary neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-beta-D-glucosaminidase (NAG), and interleukin 18 (IL-18) were found to be useful for early detection of acute kidney injury (AKI). The objective of this study was to determine the predictive ability of biomarkers for mortality and variation in levels in relation to different stages of AKI, need for dialysis, etiologies, and with duration of hospital stay. Methods Urinary NGAL, NAG, and IL-18 levels were measured in 50 children with AKI and 30 age- and gender-matched healthy controls. AKI was classified as per pediatric Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria. Results Median NGAL, NAG, and IL-18 values were significantly increased in AKI patients compared with controls (p < 0.001), with significant increase among risk, injury, and failure stages. Nonsurvivors had significantly higher median levels of NGAL (p = 0.008) and NAG (p = 0.018) than survivors. NGAL had highest area under the curve (AUC) at 0.750 [confidence interval (CI) 0.580-0.920], followed by NAG at 0.724 (CI 0.541-0.907), with sensitivity and specificity of 75 % each; and IL-18 (AUC 0.688, CI 0.511-0.864), with sensitivity 62.5 % and specificity 70.8 %, for predicting mortality. Values were significantly higher in patients who required peritoneal dialysis (PD) than in those in whom it was not indicated. Levels were comparable among different etiologies. Only NGAL level was found to be a significant risk factor associated with longer duration of hospital stay. Conclusions Urinary NGAL and NAG had modest predictive ability for mortality. Children requiring dialysis had significantly raised levels, and the NGAL level had significant association with duration of hospital stay., Author(s): Om P. Mishra [sup.1] , Avinash K. Rai [sup.1] , Pradeep Srivastava [sup.4] , Khushaboo Pandey [sup.3] , Abhishek Abhinay [sup.1] , Rajniti Prasad [sup.1] , Rabindra N Mishra [...]

Byline: Rajniti. Prasad, John. Biswas, Kulwant. Singh, Om. Mishra, Ankur. Singh Background and Aims: Brain abscess is a serious and dreadful disease presenting at tertiary centre. The objective of this [...]

Background: The aim of our study is to identify the novel targets for the SCN1A gene so that we can come up with the potential antiepileptic drugs (AEDs) with the least side effects and best efficacy. Methods: Literature review for candidate genes associated with febrile seizure, generalized epilepsy with febrile seizure plus, dravet syndrome and other idiopathic epilepsy subtypes was done using PubMed, PMC, Google Scholar, and Science Direct. Network analysis of selected candidate genes was done based on molecular function and biological processes using Cytoscape software. Selection of candidate proteins targets receptors for AEDs on the basis of first neighbor, structural retrieval analysis, and verification of selected receptors was done using Ramachandran plot analysis server (RAMPAGE) and Protein Data Bank sum server. Molecular docking calculation and analysis were performed using YASARA and BIOVIA Discovery Studio 2019 software. Results: We screened 157 epileptic genes among which 84 genes were classified as purely epileptic genes and 73 genes were classified as neurodevelopment-associated epilepsy genes. 62 childhood-onset and juvenile-onset epilepsy genes were screened excluding neonatal group due to in born errors of metabolism. In this investigation using SCN1A as a candidate gene, we found SCN9A, HCN2, and FGF12 gene-encoding proteins as potential target receptors. Further, the SCN1A protein receptor was used to screen suitable AEDs using molecular docking investigation. We got three novel AEDs against the SCN1A target gene. Conclusions: In silico network analysis has provided various best-screened target receptors from the huge network interaction group of genes for AED targeting. This will help in better understanding of disease mechanisms, analysis, and knowledge of the molecular structure of protein. [ABSTRACT FROM AUTHOR]

Background Corticosteroid therapy can cause behavioural abnormalities in children with nephrotic syndrome. The objective of this study was to explore the timing of the appearance of abnormalities in their first episode. Methods Forty-five children with a first episode of idiopathic nephrotic syndrome (30 aged 2-5 and 15 aged 6-14 years) were assessed for behavioural problems using the Child Behaviour Checklist (CBCL) before, and after 6 and 12 weeks of oral steroid treatment. Sixty healthy children were included as controls. Results In both age groups, marked abnormalities of externalising behaviour were noticed, specifically in the domains of aggressive behaviour and attention problems. Clinical range or borderline externalising abnormalities were present in 73 % of the younger children and 60 % of the schoolchildren after 6 weeks of treatment. In the schoolchildren, abnormal internalising behaviour was also noted at 6 weeks, in 40 % at borderline level and in 20 % within the clinical range. Elevated scores were observed for the anxious/depressed and withdrawn/depressed domains. Most changes persisted at the 12-week observation. Conclusions Children of both age groups showed significant attention problems and aggressive and abnormal externalising behaviour within 6 weeks of starting treatment. Parents should be informed and counselled about this potential adverse effect of steroid therapy., Author(s): Aishvarya Upadhyay[sup.1] , Om P. Mishra[sup.1] , Rajniti Prasad[sup.1] , Shashi K. Upadhyay[sup.1] , Franz Schaefer[sup.2] Author Affiliations: (1) Division of Pediatric Nephrology, Department of Pediatrics, Institute of Medical [...]