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Objective: To assess the clinical and molecular profile of patients with Duchenne Muscular Dystrophy (DMD) presenting to a tertiary center in Eastern Region of Uttar Pradesh, India., Methods: In this retrospective study, case records of all patients diagnosed as DMD were analyzed to ascertain the clinical phenotype and molecular profile. Multiplex polymerase chain reaction (mPCR) technique, Multiplex Ligation Dependent Probe Amplification (MLPA) and Next Generation Sequencing (NGS) were used for establishing the molecular diagnosis. Leiden Open Variation Database (LOVD) frame checker online tool was used to predict clinical severity of the cases., Results: Records of 112 children with DMD were analyzed. The median (IQR) age of onset and clinical presentation of disease was 60 (12, 132) months and 90 (33, 156) months, respectively. The most common clinical presentations were difficulty in standing from sitting position (n = 107), difficulty in climbing stairs (n = 106), and difficulty in walking (n = 99). Bilateral calf muscle hypertrophy and a positive Gower's sign was seen in 110 and 108 patients at presentation. The median (IQR) creatinine phosphokinase (CPK) levels at diagnosis were 6296.5 (4320, 7432.5) U/L. The genetic mutations in 111 patients were reported as deletion (n = 105), duplication (n = 3), and point variation (n = 3). 22 patients could benefit from the available exon skipping therapy. Exondys (exon 51 skipping) could be used in 14 patients., Conclusion: Deletion mutations were recorded in a much higher proportion of patients compared to previous studies from India. There were 22 patients who could have been benefitted by the available exon skipping therapy.

Introduction: This investigation aimed to thoroughly characterize the range of pulmonary function abnormalities present in individuals with Parkinson's disease (PD) and to evaluate the effects of levodopa therapy on these respiratory dysfunctions., Methods:  Ninety-five PD patients diagnosed via the UK Parkinson's Disease Society Brain Bank Diagnostic Criteria were recruited, excluding those with a smoking history or unable to perform pulmonary function tests (PFTs). Severity was assessed using the Hoehn and Yahr Scale. Spirometry-measured PFT parameters (forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow rate (PEFR)) were compared against matched predicted values. The changes in PFT parameters post-levodopa challenge were assessed., Results: Most of the PD patients were aged between 51-60 years, with a mean age of 55.89 ± 8.37 years. Of these, 65.3% were male. A significant proportion of the cohort exhibited restrictive pulmonary patterns (73.7%), while a smaller fraction displayed obstructive (7.4%) or normal (18.9%) pulmonary function patterns. Notably, levodopa treatment correlated with marked improvements in all measured PFT parameters, especially evident in the enhancements from the "off" medication stage to the "on" stage for FVC and FEV1 (P=0.0001). A weak positive correlation between the severity of respiratory restriction and the duration of PD (r = 0.139, P = 0.021) was found, suggesting that PD's progression exerts an increasingly adverse effect on respiratory function over time., Conclusion:  The findings of this study illustrate that restrictive pulmonary abnormalities are more prevalent than obstructive patterns in PD patients and that these patients respond favorably to levodopa therapy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Mishra et al.)

We report clinical and etiological profile of 19 children (10 males) with renal rickets managed in the years 2021-2022. Median (IQR) age of presentation was 60 (18-96) months. The commonest cause was renal tubular acidosis (n=8). Genetic analysis revealed the diagnosis in 83% subjects (5 out of 6 tested).

COVID-19, a highly infectious respiratory disease a used by SARS virus, has killed millions of people across many countries. To enhance quick and accurate diagnosis of COVID-19, chest X-ray (CXR) imaging methods were commonly utilized. Identifying the infection manually by radio imaging, on the other hand, was considered, extremely difficult due to the time commitment and significant risk of human error. Emerging artificial intelligence (AI) techniques promised exploration in the development of precise and as well as automated COVID-19 detection tools. Convolution neural networks (CNN), a well performing deep learning strategy tends to gain substantial favors among AI approaches for COVID-19 classification. The preprints and published studies to diagnose COVID-19 with CXR pictures using CNN and other deep learning methodologies are reviewed and critically assessed in this research. This study focused on the methodology, algorithms, and preprocessing techniques used in various deep learning architectures, as well as datasets and performance studies of several deep learning architectures used in prediction and diagnosis. Our research concludes with a list of future research directions in COVID-19 imaging categorization., Competing Interests: Conflict of interestThe authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: Idiopathic steroid resistant nephrotic syndrome (SRNS) has variable outcomes in children. The primary objective of the present study was to assess the cumulative remission rate and the secondary objectives were to assess factors affecting the remission status, kidney function survival, and adverse effects of medications., Methods: One hundred fourteen patients with SRNS were included. Calcineurin inhibitor-based treatment protocol along with prednisolone and angiotensin-converting enzyme inhibitor were used, and patients were followed over 5 years., Results: Median age was 4.5 years; 53.5% of cases were between 1 to 5 years of age. Sixty-two patients (54.4%) were at initial stage and 52 (45.6%) were at a late SRNS stage. Median eGFRcr was 83.5 mL/min/1.73m2 at presentation. Of the 110 patients, 63 (57.3%) achieved remission [complete remission 30 (27.3%), partial remission 33 (30%)], and 47 (42.7%) had no remission. Kidney function survival was 87.3% and 14 cases (12.7%) had progression to CKD (G3-8, G4-3, G5-1, and G5D-2). Median duration of follow up was 36 months (IQR 24, 60). Age of onset, cyclosporine/tacrolimus, eGFRcr, and histopathology (MCD/FSGS) did not affect remission. Similarly, remission status in addition to age of onset, drug protocol, and histopathology did not significantly affect kidney function during a period of 5 years. Hypertension, cushingoid facies, short stature, cataract, and obesity were observed in 37.7, 29.8, 25.5, 17.5, and 0.7% of cases, respectively., Conclusion: About half of the cases achieved remission. Age of onset of disease, cyclosporine/tacrolimus use, and histopathological lesion neither affected remission status nor short-term kidney function survival in SRNS.

Dengue fever is an important cause of acute febrile illness in the postmonsoon season in India. This study was done to record the incidence of dengue in admitted patients with acute febrile illness in a hospital setting. The study also intends to record the clinical, biochemical and outcome profile of paediatric dengue cases admitted in tertiary centres in Eastern Uttar Pradesh, India. It was a prospective case record analysis at a tertiary care research hospital in Eastern Uttar Pradesh. The study recruited fifty-53 children (<18 years) with serology-proven diagnosis of dengue disease. Disease was confirmed by doing Ns1Ag, IgM antibody test by ELISA method. Six hundred children were screened and 53 met the inclusion criteria. The incidence of dengue disease in hospitalised acute febrile illness was 8.8%. There were thirty-one males. The mean age of presentation of the study population was 9.32 ± 5 years with a range of 0.25 - 17 years. Fever (94%), nausea and vomiting (59 %), abdominal pain (55%), persistent vomiting (49%), thrombocytopenia (<100,000 [66%]), and petechiae and purpura (43%) were the important clinical manifestations. Six required intensive care monitoring. There was only one death. Dengue fever is an important cause of acute febrile illness in children. Case fatality rate can be minimised with proper World Health Organisation classification and protocol-based management of cases., Competing Interests: The authors declare that they have no competing interests., (Copyright © Sudanese Association of Pediatricians.)

Objective: To find out the serum fibroblast growth factor 23 (FGF-23) levels in different grades of CKD, and the prevalence of abnormal left ventricular mass index (LVMI), carotid intima-medial thickness (cIMT), and central pulse wave velocity (cPWV) and the risk factors including FGF-23 for these abnormalities., Methods: Fifty-nine patients of CKD with G2 to G5, aged 2-18 y were included. The LVMI, cIMT, and cPWV were measured using standard techniques, and serum intact FGF-23 levels were estimated at enrollment., Results: Median FGF-23 levels were significantly raised in all the grades of CKD than controls (p < 0.001), and also in G4 and G5 in comparison to G2&3 and in G5D than G5. Increased LVMI in 42 (71.2%), elevated cIMT in 30 (57.7%), and cPWV in 14 (26.9%) patients were found. The FGF-23 showed significant negative correlation with eGFRcr and positive with serum iPTH, phosphate and alkaline phosphatase levels, but had no correlations with LVMI, cIMT SDS, and cPWV SDS. Only systolic BP SDS (odds ratio 1.5, 95% CI 1.008-2.231, p = 0.046) was observed as a significant predictor for increased cIMT, while no variables had any association with abnormal LVMI and cPWV., Conclusions: Serum FGF-23 showed higher levels with increasing grades of CKD, but no significant association with cardiovascular parameters. Systolic BP SDS was found as a significant risk factor for increased cIMT in children with CKD., (© 2021. Dr. K C Chaudhuri Foundation.)

Infants with acute kidney injury (AKI) who are critically ill often will have multiorgan dysfunctions. Objective of the present study was to find out mortality, recovery of kidney function at discharge and at 3 months, and to determine risk factors for mortality. Fifty-two infants (24 newborns and 28 postneonatal) with AKI were included. Staging was done as per Kidney Disease Improving Global Outcomes classification. Patients were subjected to medical treatment and peritoneal dialysis (PD), wherever indicated. Kidney function tests were performed at admission, discharge, and at 3 months follow-up. Median age of neonates was 8 days and postneonatal infants were 4.5 months. Stage 1, 2, and 3 AKI were present in 14 (26.9%), 16 (30.7%), and 22 (42.3%) cases, respectively. PD was required in 22 (42.3%) infants, and significantly higher in postneonatal than in neonates (57.1% vs. 25%, p < 0.05). Significant recovery of kidney function occurred at discharge and cases had normal parameters at 3 months. Mortality was 17.3%. Patients had significantly higher risk of mortality, if they had metabolic acidosis (OR 13.22, CI 2.33-74.94, p = 0.002) and needed ventilation (OR 14.93, 95% CI 1.7-130.97, p = 0.006) and PD (OR 6.53, 95% CI 1.20-35.48, p = 0.026). In logistic regression analysis, fluid overload (p < 001), hypotension (p < 0.01), and higher PRISM-III score (p < 0.05) were found as significant risk factors for mortality. Medical management including PD led to good recovery of kidney function. Presence of fluid overload, hypotension, and higher PRISM-III score adversely affected the outcome., (© 2021 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

This study evaluated the diagnostic role of cerebrospinal fluid leucine-rich alpha-2 glycoprotein (CSF LRG) concentration in children with acute bacterial meningitis, and its role in differentiation from aseptic meningitis. CSF LRG concentration was measured by ELISA Kit of 50 children with bacterial meningitis, 16 aseptic meningitis, and 20 children with normal CSF; control. CSF LRG was significantly elevated (p < 0.001) in bacterial meningitis with a sensitivity, specificity, PPV, and NPV of 96%, 100%, 100%, and 90.9%, respectively at a cutoff of 110.0 ng/mL, based on ROC curve. At the same cutoff value, CSF LRG has sensitivity, specificity, PPV, and NPV of 96%, 75%, 92.3%, and 85.7%, respectively in differentiating bacterial from aseptic meningitis. However, sensitivity, specificity, PPV, and NPV at 139.9 ng/mL for differentiating between definite and probable bacterial meningitis were 88%, 75%, 79.1%, and 84.9%, respectively. CSF LRG should be used as a diagnostic biomarker for bacterial meningitis., (© 2021. Dr. K C Chaudhuri Foundation.)

Introduction: Treatment of nephrotic syndrome with corticosteroid can cause several side- effects including behavioral abnormalities. The objectives of the study were to observe the proportion of non-relapsers having persistence of behavioral abnormalities after completion of treatment of initial episode and compare the abnormalities with relapsers, and to determine risk factors for persistence., Methods: Seventy-five children with a first episode of idiopathic nephrotic syndrome and 60 normal children were rated by parents for behavioral problems using the Child Behavior Checklist. The Parenting Stress Index was also evaluated. The children were rated before treatment and 12 and 36 weeks after., Results: Both relapsers and non-relapsers showed abnormalities in internalizing and externalizing domains at 12 weeks of steroid therapy. Non-relapsers had abnormal scores in the internalizing domain in 63.5 % and externalizing domain in 48.1% of cases at 36 weeks. Relapsers had abnormal scores in all the three behavior domains, but a significantly higher proportion of relapsers had abnormal scores regarding total behavior (65.2% vs 28.8%, p<0.01) and child domains (100% vs 57.7%, p<0.001) of Parenting Stress Index in comparison to non-relapsers at 36 weeks. Occurrence of relapse increased the risk (odds ratio 5.76, 95% CI 1.35-10.76, p< 0.001) for persistence of abnormal total behavior at 36 weeks follow-up., Conclusion: Persistence of abnormalities was observed not only in relapsers but also in non-relapsers. Relapse was found to be a significant risk factor for persistence of abnormal behaviors in these patients.

Background: Albumin is the major protein excreted in urine in patients with nephrotic syndrome (NS). However, low-molecular-weight proteins including some binding proteins are also excreted. Thyroid hormone and its binding globulins are excreted in urine in excess in nephrotic syndrome. Therefore, it has been postulated that patients with nephrotic syndrome may show hypothyroidism, subclinical or overt., Methods: In this prospective observational study, patients of idiopathic nephrotic syndrome aged 1-40 years of both gender were included. Serum T3, T4 and TSH were assayed at diagnosis and repeated at 12 weeks or at remission whichever was earlier. Renal biopsy was performed as required., Results: Among 100 patients taken for analysis (42 children, 58 adult), 30 cases were of first episode, 40 were of frequent relapse/steroid-dependent NS, and 30 patients had steroid-resistant NS (SRNS). Three (3%) cases had overt hypothyroidism and 18 (18%) patients had subclinical hypothyroidism. Most hypothyroid cases belonged to SRNS subgroup. Mean Serum T3, T4 and TSH values showed significant improvement in remission in comparison to nephrosis state (P < 0.01). Serum TSH had significant positive correlation (r = 0.391, P < 0.01) with 24-h proteinuria and negative correlation with serum albumin (r =  - 0.303, P < 0.01) in nephrosis., Conclusion: Hypothyroidism is common among nephrotic syndrome patients especially in SRNS subgroup. Therefore, routine screening is recommended in steroid-resistant nephrotic syndrome patients., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.)

Background: Social media platforms such as Facebook, WhatsApp, and Instagram etc., are becoming very popular now not only for youth but for all walks of life. People are more often seen in busy in tweeting, chatting, or putting selfies. No one actually knows the mental state of a person in the online platform. In this article, we will be focusing on how social media is affecting issues such as road accident, murder, and suicide. The research is done by three parts., Materials and Methods: Google Form analysis, machine learning used for prediction, and by sentimental analysis of what people think in twitter. All the datasets are based in India. From these datasets, the different machine learning algorithm is used to do the analysis. The project strives to bring the real-world solution in the matter of advancement., Results: The static data analysis and dynamic data analysis shows the various sentimental analysis and predictions and the technique to predict different mental states. Thus we get clearly about the current world is getting into social issues. This research findings helps to bring social awareness among the current generation by understanding the sensitivity of the youths., Conclusion: Thus through this paper we get known clearly how the current world is getting into social issues like victim of murders or road accidents or committing suicide. The paper clearly helps us to understand the sensitivity of the youths. Therefore brings a social awareness among the current generation., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Education and Health Promotion.)

Metal-oxide nanoparticles (MO-NPs), such as the highly bioreactive copper-based nanoparticles (CuO-NPs), are widely used in manufacturing of hundreds of commercial products. Epidemiological studies correlated levels of nanoparticles in ambient air with a significant increase in lung disease. CuO-NPs, specifically, were among the most potent in a set of metal-oxides and carbons studied in parallel regarding DNA damage and cytotoxicity. Despite advances in nanotoxicology research and the characterization of their toxicity, the exact mechanism(s) of toxicity are yet to be defined. We identified chlorination toxicity as a damaging consequence of inflammation and myeloperoxidase (MPO) activation, resulting in macromolecular damage and cell damage/death. We hypothesized that the inhalation of CuO-NPs elicits an inflammatory response resulting in chlorination damage in cells and lung tissues. We further tested the protective action of LGM2605, a synthetic small molecule with known scavenging properties for reactive oxygen species (ROS), but most importantly, for active chlorine species (ACS) and an inhibitor of MPO. CuO-NPs (15 µg/bolus) were instilled intranasally in mice and the kinetics of the inflammatory response in lungs was evaluated 1, 3, and 7 days later. Evaluation of the protective action of LGM2605 was performed at 24 h post-challenge, which was selected as the peak acute inflammatory response to CuO-NP. LGM2605 was given daily via gavage to mice starting 2 days prior to the time of the insult (100 mg/kg). CuO-NPs induced a significant inflammatory influx, inflammasome-relevant cytokine release, and chlorination damage in mouse lungs, which was mitigated by the action of LGM2605. Preventive action of LGM2605 ameliorated the adverse effects of CuO-NP in lung.

This retrospective study describes the clinical profile, risk of infection and outcome of coronavirus disease-19 in immuno-compromised children. It was found that children on immuno-suppressant medication has 2.89 times increased risk of infection (P=0.01). Disease manifestation was asymptomatic (P=0.01) or mild with predominant gastrointestinal symptoms (P=0.02) without alteration in immunosuppressive treatment regime.

Competing Interests: There are no conflicts of interest.

Justification: Steroid sensitive nephrotic syndrome (SSNS) is one of the most common chronic kidney diseases in children. These guidelines update the existing Indian Society of Pediatric Nephrology recommendations on its management., Objective: To frame revised guidelines on diagnosis, evaluation, management and supportive care of patients with the illness., Process: The guidelines combine evidence-based recommendations and expert opinion. Formulation of key questions was followed by review of literature and evaluation of evidence by experts in two face-to-face meetings., Recommendations: The initial statements provide advice for evaluation at onset and follow up and indications for kidney biopsy. Subsequent statements provide recommendations for management of the first episode of illness and of disease relapses. Recommendations on the use of immunosuppressive strategies in patients with frequent relapses and steroid dependence are accompanied by suggestions for step-wise approach and plan of monitoring. Guidance is also provided regarding the management of common complications including edema, hypovolemia and serious infections. Advice on immunization and transition of care is given. The revised guideline is intended to improve the management and outcomes of patients with SSNS, and provide directions for future research.

Steroid-resistant nephrotic syndrome (SRNS) patients with genetic mutations most commonly have histology of focal segmental glomerulosclerosis (FSGS) and do not respond to immunosuppressive drugs. We report the molecular screening results of 18 pediatric SRNS cases presented to our nephrology clinic. Three pathogenic variants have been detected, two previously reported and one novel variant. The reported pathogenic variants have been detected in NPHS1 and NPHS2 genes. A novel pathogenic variant has been detected in the inverted formin 2 gene ( INF2 ) gene. We did not detect any variant of the WT1 gene. There were 13 males. Mean age of study participants at enrollment was 69 months. There were 12 cases of primary SRNS. The mean duration from onset of symptoms to SRNS diagnosis was 13 months. FSGS and minimal change disease (MCD) were present in the same number of cases. The response rate (complete or partial) to immunosuppressive drugs was seen in only one patient in the genetic SRNS group ( n  = 3), while the response rate in nongenetic cases ( n  = 15) was 80%. Two nonresponders in the genetic SRNS group had FSGS for histopathology and pathogenic variants (NPHS2 and INF2). The other three nonresponders in the nongenetic SRNS group had both FSGS ( n  = 1) and MCD ( n  = 2) histopathology. There were two deaths in the study cohort of the nongenetic SRNS group. This study highlights the screening of the SRNS cohort by a panel of extended genes rather focussing on the three most common genes ( NPHS1 , NPHS2 , and WT1 ). This further confirms the molecular etiology of SRNS in three cases and extends the list of pathogenic variants of genetic SRNS in the North Indian population. This is the first study in the eastern part of Uttar Pradesh in India., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

This research was carried out with an objective to examine the efficacy of ultrafiltered xylano-pectinolytic enzymes in pulping of sugarcane bagasse. Maximum biopulping was achieved with enzyme dose of xylanase (175 IU / g bagasse) and pectinase (75 IU / g bagasse) at treatment period of 180 min. The temperature, pH, and bagasse to liquid ratio for biopulping experiments were kept constant at 55 o C, 8.5, and 1:10 (g/ml), respectively. The ultrafiltered biopulping improved chemical pulping, resulted in 25.11%, 9.17% increase in brightness, unscreened pulp production and 11.81, 59.50, and 49.14% decrease in total solids, rejections. and kappa number, respectively. The bagasse biopulping also resulted in 15% decrease of alkali load to attain similar kappa number and optical properties as obtained under 100% alkali dosage. Ultrafiltered biopulped-unbleached samples showed significant increase in breaking length (13.55%), burst index (40.21%), tear index (19.04%), double fold (42.5%), Gurley porosity (28.21%) and viscosity (13.37%) in comparison with non-enzymatically treated control pulp samples. In comparison with non biotreated-bleached pulp samples, ultrafiltered biopulped-bleached samples also resulted in higher burst index (56.80%), breaking length (17.38%), double fold (39.58%), tear index (3.38%), viscosity (30.68%), and Gurley porosity (52.50%). This environmentally sustainable ultrafiltered biopulping approach for sugarcane bagasse has the potential to decrease the demand of chemicals, ultimately pollution along with enhance the quality of paper.

In this study, suitability of xylano-pectinolytic enzymes in pulping of wheat straw has been explored. The suitable biopulping conditions were optimized, with xylanase dose of 400 and pectinase dose of 120 IU/g wheat straw, 1:10 (g/ml) material to liquid ratio, 55 °C temperature, 3 h treatment time, 0.75% Tween 80 and pH 8.5. Enzymatic pretreatment efficiently increased the pulpability of wheat straw, generated pulp with higher yield, lower kappa number (15.67%) and rejections (59.65%) in comparison with chemical pulp. The brightness of pretreated wheat straw pulp with enzyme was 16.04% higher than that of the non-enzyme treated wheat straw pulp. The biopulping resulted in 12% reduction of pulping chemicals along with more residual alkali content, in order to achieve similar optical and chemical properties as obtained by 100% chemically treated pulp. Physical properties of pulp also improved after enzymatic pretreatment, increasing burst index (26.50%), tear index (18.22%) and breaking length (5.56%). The enzyme plus chemical (88% pulping chemicals) treated pulp showed improvement in brightness and whiteness, with reduction in yellowness at all bleaching stages. In comparison with chemically bleached pulp, biopulp with reduced alkali dose (88%) had higher breaking length (6.63%), double fold number (51.28%), tear index (2.83%), burst index (24.31%), along with increased viscosity (6.12%) and Gurley porosity (27.50%). These results clearly suggest that biopulping of wheat straw with xylano-pectinolytic enzymes can reduce chemical loading during soda-anthraquinone pulping and also improve the quality of paper. This is the first report demonstrating the biopulping of wheat straw using crude xylano-pectinolytic enzymes.

The coronavirus outbreak is a rapidly evolving pandemic, placing unprecedented strain on health-care systems. COVID-19 presents challenges for management of children with renal diseases, especially those receiving long-term immunosuppressive medications, including renal transplant recipients and those with chronic kidney disease and acute kidney injury requiring dialysis. Our preparedness for managing this vulnerable group of children is the need of the hour. The purpose of this article is to provide guidance to caregivers and health care personnel involved in management of children with renal diseases and to ensure patient well-being, while protecting staff from infection.

Background: Radiation exposure of tissues is associated with inflammatory cell influx. Myeloperoxidase (MPO) is an enzyme expressed in granulocytes, such as neutrophils (PMN) and macrophages, responsible for active chlorine species (ACS) generation. The present study aimed to: 1) determine whether exposure to γ-irradiation induces MPO-dependent ACS generation in murine PMN; 2) elucidate the mechanism of radiation-induced ACS generation; and 3) evaluate the effect of the synthetic lignan LGM2605, known for ACS scavenging properties., Methods: MPO-dependent ACS generation was determined by using hypochlorite-specific 3'-(p-aminophenyl) fluorescein (APF) and a highly potent MPO inhibitor, 4-aminobenzoic acid hydrazide (ABAH), and confirmed in PMN derived from MPO -/- mice. Radiation-induced MPO activation was determined by EPR spectroscopy and computational analysis identified tyrosine, serine, and threonine residues near MPO's active site., Results: γ-radiation increased MPO-dependent ACS generation dose-dependently in human MPO and in wild-type murine PMN, but not in PMN from MPO -/- mice. LGM2605 decreased radiation-induced, MPO-dependent ACS. Protein tyrosine phosphatase (PTP) and protein serine/threonine phosphatase (PSTP) inhibitors decreased the radiation-induced increase in ACS. Peroxidase cycle results demonstrate that tyrosine phosphorylation blocks MPO Compound I formation by preventing catalysis on H 2 O 2 in the active site of MPO. EPR data demonstrate that γ-radiation increased tyrosyl radical species formation in a dose-dependent manner., Conclusions: We demonstrate that γ-radiation induces MPO-dependent generation of ACS, which is dependent, at least in part, by protein tyrosine and Ser/Thr dephosphorylation and is reduced by LGM2605. This study identified for the first time a novel protein dephosphorylation-dependent mechanism of radiation-induced MPO activation., Competing Interests: Declaration of Competing Interest Melpo Christofidou-Solomidou (MCS) reports grants from the National Institutes of Health (NIH) and the National Aeronautics and Space Administration (NASA) during the conduct of the study. In addition, MCS has patents No. US 10,045,951 B2, No. US 10,030,040 B2, and No. US 9,987,321 B2 issued and patents No. PCT/US2016/049780, No. PCT/US17/35960, and No. PCT/US2008/006694 pending, and has a founders equity position in LignaMed, LLC. MCS, AVP, and MA report grants from the NIH during the conduct of the study. RAP, W-TH, ENO, and OPM have nothing to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Lysosomal storage disorders (LSDs) are relatively common slow progressive inborn error of metabolism encountered by clinicians. This work intends to highlight the more common LSDs, their clinical presentation, outcome, and mutation (wherever feasible) collected from the genetic clinic at tertiary care center in Eastern Uttar Pradesh. The data for analysis were collected retrospectively from genetic records from a follow-up clinic. All cases < 18 years of age were analyzed. Cases with LSDs with confirmed enzyme results were enrolled in this study. Clinical profile, screening test results, and outcome were collected. There were 32 cases including 27 males and 5 females in this cohort: 8 Gaucher disease (GD) patient and 24 non-GD patients. GD (type 1) is the commonest LSD in GD group. Anemia, thrombocytopenia, splenomegaly, and hepatomegaly were the consistent finding in patients with GD (type 1). L483P mutation was reported in two GD patients. One GD patient is on enzyme replacement therapy for 2 years and is currently doing well. The commonest disorders in non-GD were mucopolysaccharidosis (MPS) ( n  = 11), metachromatic leukodystrophy ( n  = 4), I-cell disease ( n  = 3), Niemann-Pick A/B ( n  = 3). MPS-II is the commonest MPS among non-GD group., Competing Interests: Conflict of Interest None declared., (© Thieme Medical Publishers.)

Background and Aims: Brain abscess is a serious and dreadful disease presenting at tertiary centre. The objective of this study was to look into the clinical profile, predisposing conditions, microbiology and outcome of children suffering from brain abscess., Methods: 30 children up to 18 years with clinical and imaging evidence of brain abscess were taken for study. Patients were stabilized as per unit protocol. Necessary investigations were carried out. Neuroimaging (CT or MRI) was used to confirm the diagnosis. All parameters (clinical, investigation, outcome) were recorded in predesigned performa. Neurosurgery consultation was sought in patients with multiple abscesses, posterior fossa abscesses, abscess with air-fluid level and causing midline shift., Results: There were 16 males with 13 patients in age group (5-10 years). Mean duration of stay in hospital was 14.8 days. Most common predisposing factor was chronic suppurative otitis media (n-15). Typically, patients presented with fever, headache and seizures. On examination, motor deficits were the most common followed by signs of meningitis. Computerized tomography confirmed the diagnosis in most cases. Temporal lobe (n-11) was the commonest intracranial site for the abscess. Methicillin resistant staphylococcus and proteus mirabilis were the common pathogen isolated from blood and pus. Blood culture positivity rate was 16.7% and pus culture positivity rate was 25%. All cases were managed with intravenous antibiotics and aspiration (n-10) and excision (n-6). There were 5 deaths. There was complete immediate recovery in 13 cases with residual motor deficit in 12 cases., Conclusion: Brain abscess is a rare but serious entity in children. Late diagnosis and improper management leads to poor outcome. Early surgical intervention is helpful. Threshold for diagnosis should be low in children with chronic ear infection and congenital heart diseases., Competing Interests: There are no conflicts of interest., (Copyright: © 2006 - 2020 Annals of Indian Academy of Neurology.)

Introduction: Childhood tuberculosis (TB) is now a global priority. With the advent of Xpert MTB/RIF, more TB cases in children are being reported. This study was undertaken to evaluate the performance of Xpert in diagnosis of pulmonary and extra-pulmonary TB in children., Methods: Specimens from 171 suspected TB cases in children aged <15 years were tested with Xpert, culture and smear microscopy in the Department of Microbiology, Institute of Medical Sciences, India., Results: The specimens included 106 gastric aspirates, 51 cerebrospinal fluids, 8 induced sputum and 6 lymph node aspirates. Xpert detected Mycobacterium tuberculosis in 19 cases (14 pulmonary and 5 extra-pulmonary), 7 of which were rifampicin-resistant. Sensitivity, specificity, positive predictive value and negative predictive value of Xpert compared with culture were 88.89, 98.04, 84.21 and 98.68%, respectively. The sensitivity was 100% in children aged 1-5 years and 6-10 years and in gastric aspirates., Conclusion: Xpert is an efficient diagnostic tool in childhood tuberculosis.

Objectives: To detect Cytotoxic T- Lymphocyte Antigen-4 (CTLA4) single nucleotide polymorphisms (SNPs) at +49A/G (rs231775) and -318C/T (rs5742909) positions in children with idiopathic nephrotic syndrome (INS) and also assay urinary soluble CTLA4 (sCTLA4) levels in children with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) and steroid sensitive nephrotic syndrome (SSNS) in remission., Methods: The study included 59 patients of INS (MCD-23, FSGS-15 and SSNS in remission-21) and 35 healthy controls. The CTLA4 SNPs profiling was done in peripheral blood mononuclear cells and urinary sCTLA4 level was assayed by ELISA kit., Results: Although frequency of homozygous +49 GG (rs4553808) genotype (26.3% vs. 11.4%; p = 0.231) and G allele (52.6% vs. 40%; p = 0.216) were found to be higher in INS as compared to controls, the differences were statistically non-significant. Genotypes GG, AG, AA and alleles A and G frequencies were comparable among MCD, FSGS and controls. SNP at -318 C/T (rs5742909) did not show homozygous TT genotype both in INS as well as controls. Median urinary sCTLA4/creatinine level was significantly higher in MCD as compared to FSGS (p = 0.027), SSNS in remission (p = 0.001) and controls (p = 0.003)., Conclusions: The positive associations of +49 GG genotype and G allele in patients with nephrotic syndrome were not observed. The frequencies did not differ significantly among MCD, FSGS and controls. Urinary sCTLA4 level was significantly increased in MCD; suggesting its possible role in the pathogenesis of disease.

Background: Myeloperoxidase (MPO) generates hypochlorous acid (HOCl) during inflammation and infection. We showed that secoisolariciresinol diglucoside (SDG) scavenges radiation-induced HOCl in physiological solutions. However, the action of SDG and its synthetic version, LGM2605, on MPO-catalyzed generation of HOCl is unknown. The present study evaluated the effect of LGM2605 on human MPO, and murine MPO from macrophages and neutrophils., Methods: MPO activity was determined fluorometrically using hypochlorite-specific 3'-(p-aminophenyl) fluorescein (APF). The effect of LGM2605 on (a) the peroxidase cycle of MPO was determined using Amplex Red while the effect on (b) the chlorination cycle was determined using a taurine chloramine assay. Using electron paramagnetic resonance (EPR) spectroscopy we determined the effect of LGM2605 on the EPR signals of MPO. Finally, computational docking of SDG was used to identify energetically favorable docking poses to enzyme's active site., Results: LGM2605 inhibited human and murine MPO activity. MPO inhibition was observed in the absence and presence of Cl - . EPR confirmed that LGM2605 suppressed the formation of Compound I, an oxoiron (IV) intermediate [Fe(IV)O] containing a porphyrin π-radical of MPO's catalytic cycle. Computational docking revealed that SDG can act as an inhibitor by binding to the enzyme's active site., Conclusions: We conclude that LGM2605 inhibits MPO activity by suppressing both the peroxidase and chlorination cycles. EPR analysis demonstrated that LGM2605 inhibits MPO by decreasing the formation of the highly oxidative Compound I. This study identifies a novel mechanism of LGM2605 action as an inhibitor of MPO and indicates that LGM2605 may be a promising attenuator of oxidant-dependent inflammatory tissue damage., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Forty cases with disproportionate short stature (median age 3.1 y; 24 males) from genetic clinic of Lok Nayak Hospital, Delhi were assessed in this study. Achondroplasia was the commonest (n=9) skeletal dysplasia; conclusive diagnosis was not possible in six children. Molecular confirmation of clinicoradiological phenotype was done in 18 of 40 cases. Genetic study of all achondroplasia cases revealed c. 1138 G>A, p. Gly380Arg mutation in hot spot.

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.

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.

Objective: To assess prevalence of behavioral problems in children with epilepsy., Methods: This was a cross-sectional study of children with epilepsy, and normal controls enrolled between July 2013 to June 2015. Child Behavior Checklist (CBCL) was used as a tool to assess the behavior based on parents reported observation., Results: There were 60 children with epilepsy in 2-5 years and 80 in 6-14 years age groups, and 74 and 83 unaffected controls, respectively. Mean CBCL scores for most of the domains in children of both age groups were significantly higher than controls. Clinical range abnormalities were mainly detected in externalizing domain (23.3%) in 2-5 years, and in both internalizing (21.2%) and externalizing (45%) domains in children of 6-14 years. Younger age of onset, frequency of seizures and duration of disease had significant correlation with behavioral problems in both the age groups. Antiepileptic drug polytherapy was significantly associated with internalizing problems in older children., Conclusion: Age at onset, frequency of seizures and duration of disease were found to be significantly associated with occurrence of behavioral problems.

Mucopolysaccharidosis (MPS) and Mucolipidosis (ML) share common phenotypes (coarse facial features, organomegaly, dysostosis multiplex) despite having different molecular basis. Thus, they pose great diagnostic challenge to treating clinicians. Differentiating between the two conditions requires a battery of tests from screening to molecular diagnosis. Besides discussing differential diagnosis of MPS like features with negative urinary Glycosaminoglycans (GAG), the authors also discuss the utility of p-nitrocatechol sulphate based chemical test as an important screening tool, besides establishing molecular basis in index case.