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Iron (Fe) and zinc (Zn) deficiency has been identified as a major food-related health issue, affecting two billion people globally. Efforts to enhance the Fe and Zn content in food grains through plant breeding are an economic and sustainable solution to combat micronutrient deficiency in resource-poor populace of Asia and Africa. Pearl millet, Cenchrus americanus (L). Morrone, considered as a hardy nutri-cereal, is the major food crop for millions of people of these nations. As an effort to enhance its grain mineral content, an investigation was conducted using line × tester analysis to generate information on the extent of heterosis, gene action, combining ability for grain yield potential, and grain mineral nutrients (Fe and Zn). The partitioning of variance attributable to parents indicated that the lines and testers differed significantly for the traits studied. For most of the attributes, hybrids that were superior to the parents in the desired direction in terms of per se performance were identified. The analysis of combining ability variance indicated the preponderance of both additive and non-additive genetic effects. Thus, reciprocal recurrent selection can be used to develop a population with high-grain Fe and Zn contents. The Fe and Zn content in grain exhibited a highly significant and positive association between them, whereas the Fe and Zn contents individually showed a negative, albeit weak, correlation with grain yield and a moderate positive relation with grain weight. This indicates that mineral nutrient contents in grains can be improved without significant compromise on yield. The consistency of these trends across the environment suggests that these findings could be directly used as guiding principles for the genetic enhancement of Fe and Zn grain content in pearl millet., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Thribhuvan, Singh, Sankar, Singh, Mallik, Singhal, Meena and Satyavathi.)

Objective: To evaluate metabolic and genetic abnormalities in children with nephrolithiasis attending a referral center in North India., Methods: The patients aged 1-18 y old with nephrolithiasis underwent biochemical evaluation and whole-exome sequencing. The authors evaluated for monogenic variants in 56 genes and compared allele frequency of 39 reported polymorphisms between patients and 1739 controls from the GenomeAsia 100 K database., Results: Fifty-four patients, aged 9.1 ± 3.7 y were included. Stones were bilateral in 42.6%, familial in 33.3%, and recurrent in 25.9%. The most common metabolic abnormalities were hypercalciuria (35.2%), hyperoxaluria (24.1%), or both (11.1%), while xanthinuria (n = 3), cystinuria (n = 1), and hyperuricosuria (n = 1) were rare. Exome sequencing identified an etiology in 6 (11.1%) patients with pathogenic/likely pathogenic causative variants. Three variants in MOCOS and one in ATP7B were pathogenic; likely pathogenic variants included MOCOS (n = 2), AGXT, and SLC7A9 (n = 1, each). Causality was not attributed to two SLC34A1 likely pathogenic variants, due to lack of matching phenotype and dominant family history. Compared to controls, allele frequency of the polymorphism TRPV5 rs4252402 was significantly higher in familial stone disease (allele frequency 0.47 versus 0.53; OR 3.2, p = 0.0001)., Conclusion: The chief metabolic abnormalities were hypercalciuria and hyperoxaluria. A monogenic etiology was identified in 11% with pathogenic or likely pathogenic variants using a gene panel for nephrolithiasis. Heterozygous missense variants in the sodium-phosphate cotransporter SLC34A1 were common and required evaluation for attributing pathogenicity. Rare polymorphisms in TRPV5 might increase the risk of familial stones. These findings suggest that a combination of metabolic and genetic evaluation is useful for determining the etiology of nephrolithiasis., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Purpose: Although unexpected airway difficulties are reported in patients with mucormycosis, the literature on airway management in patients with mucormycosis associated with Coronavirus disease is sparse., Methods: In this retrospective case record review of 57 patients who underwent surgery for mucormycosis associated with coronavirus disease, we aimed to evaluate the demographics, airway management, procedural data, and in-hospital mortality records., Results: Forty-one (71.9%) patients had a diagnosis of sino-nasal mucormycosis, fourteen (24.6%) patients had a diagnosis of rhino-orbital mucormycosis, and 2 (3.5%) patients had a diagnosis of palatal mucormycosis. A total of 44 (77.2%) patients had co-morbidities. The most common co-morbidities were diabetes mellitus in 42 (73.6%) patients, followed by hypertension in 21 (36.8%) patients, and acute kidney injury in 14 (28.1%) patients. We used the intubation difficulty scale score to assess intubating conditions. Intubation was easy to slightly difficult in 53 (92.9%) patients. In our study, mortality occurred in 7 (12.3%) patients. The median (range) mortality time was 60 (27-74) days. The median (range) time to hospital discharge was 53.5 (10-85) days. The median [interquartile range] age of discharged versus expired patients was 47.5 [41,57.5] versus 64 [47,70] years (P = 0.04), and median (interquartile range) D-dimer levels in discharged versus expired patients was 364 [213, 638] versus 2448 [408,3301] ng/mL (P = 0.03)., Conclusion: In patients undergoing surgery for mucormycosis associated with the coronavirus disease, airway management was easy to slightly difficult in most patients. Perioperative complications can be minimized by taking timely and precautionary measures., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest., (Copyright © 2022 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

Objective: Severe edema in children with nephrotic syndrome is often refractory to conventional diuretics. Tolvaptan has been used satisfactorily for managing edema in patients with heart failure and cirrhosis. The safety and efficacy of combination therapy with oral tolvaptan and intravenous (IV) furosemide was assessed in patients with furosemide refractory edema., Methods: Patients, aged 5-18 y with nephrotic syndrome and severe edema, were screened for eligibility. After excluding hypovolemia, patients received IV furosemide (3-4 mg/kg/d) for 48 h. Those refractory to IV furosemide (weight loss < 3%) received tolvaptan (0.5-1 mg/kg once daily) and IV furosemide for the next 48 h. Parameters were compared between 48 h of furosemide alone and combination therapy., Results: A total of 24 patients (18 boys) with mean age of 8.0 ± 3.0 y were enrolled. Urine volume significantly increased with combination therapy as compared to furosemide therapy (mean difference: 1.2 mL/kg/h; 95% CI: 0.8-1.65 mL/kg/h) (p < 0.001). Compared to therapy with furosemide alone, combination therapy resulted in significant reduction in body weight from 26.9 ± 10.3 kg to 24.8 ± 9.7 kg (p < 0.001). Estimated glomerular filtration rate did not change (p = 0.81) but serum sodium increased from 135.7 ± 3.3 mEq/L to 140.4 ± 4.8 mEq/L (p < 0.001) with combination therapy; 2 patients showed asymptomatic hypernatremia., Conclusion: The combination of oral tolvaptan and IV furosemide is effective in augmenting diuresis and reducing weight in patients with furosemide refractory edema but requires monitoring of electrolytes and volume status., (© 2021. Dr. K C Chaudhuri Foundation.)

Early recognition of patients at risk for severe acute kidney injury (AKI) by renal angina index (RAI) may help in the early institution of preventive measures. Objective was to evaluate performance of RAI alone or in combination with biomarkers in predicting severe AKI (KDIGO stage 2 and 3 or equivalent) and receipt of kidney replacement therapy (KRT) in critically ill children. We searched PubMed, EMBASE, Web of Sciences, and CENTRAL for studies published till May 2021. Search terms included acute kidney injury, pediatrics, adolescent, renal angina index, and biomarker. Proceedings of relevant conferences and references of included studies were also scrutinized. Two reviewers independently assessed the study eligibility. Cohort and cross-sectional studies evaluating the diagnostic performance of RAI in predicting AKI or receipt of KRT in children were included. Eligible participants were the children less than 18 years with RAI assessment on day 0 ofadmission. We followed PRISMA-DTA guidelines and used the QUADAS-2 tool for quality assessment. A bivariate model for meta-analysis was used to calculate the summary estimates of diagnostic parameters. Major outcomes were the diagnostic accuracy of RAI (≥ 8) alone or with biomarkers in predicting severe AKI and KRT receipt. Diagnostic accuracy was reported using summary sensitivity, specificity, and area under the curve (AUC). Overall, 22 studies (24 reports, 14,001 participants) were included. RAI ≥ 8 on day 0 has summary sensitivity, specificity, and AUC of 0.86 (95% CI, 0.77-0.92), 0.77 (0.68-0.83), and 0.88 (0.85-0.91) respectively for prediction of severe AKI on day 3. In comparison, a combination of RAI and urinary neutrophil gelatinase-associated lipocalin (NGAL) showed summary sensitivity, specificity, and AUC of 0.76 (0.62-0.85), 0.89 (0.74-0.96), and 0.87 (0.84-0.90) respectively for predicting severe AKI. The sensitivity, specificity, and AUC of RAI for predicting receipt of KRT were 0.82 (0.71-0.90), 0.74 (0.66-0.81), and 0.85 (0.81-0.88) respectively. In meta-regression, only the study setting (sepsis vs. heterogenous) was associated with heterogeneity. We observed substantial heterogeneity among eligible studies. Five studies had concerns in patient selection, and seven studies also had applicability concerns in patient selection for this review. Moderate certainty evidence showed that RAI ≥ 8 has good predicting ability in recognizing children at risk of severe AKI and receipt of KRT. The combination of urinary NGAL and RAI further improves the predicting ability (low-certainty evidence). Further studies are required on the context-driven assessment of novel biomarkers in the early prediction of AKI in RAI-positive children. Systematic review registration number: CRD4202122268. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2021. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Evidence from randomized controlled trials (RCTs) suggests that three-hourly feeding is safe and might help achieve full feeds earlier in preterm infants. We systematically compared the benefits and harms of three-hourly and two-hourly feeding schedules in preterm infants. We searched electronic databases (MEDLINE, CINAHL, Embase, Web of Science, and Scopus) and trial registries until November 16, 2021, for RCTs comparing the two feeding schedules. We did a random-effects meta-analysis using RevMan 5.4 software. The primary outcome was the incidence of stage II or III necrotizing enterocolitis (NEC). Other outcomes were the incidence of any stage NEC, mortality, time to full enteral feeds, and hospital stay. Six trials (872 participants) are included. There was no significant difference in the incidence of stage II/III NEC (3 trials; 530 participants; RR 1.39; 95% CI: 0.53, 3.65; I 2  - 0%, low certainty), and any stage NEC (5 studies; 767 participants; RR 0.98; 95% CI: 0.53, 1.82; I 2 -0%, very low certainty) between three and two-hourly feeding groups. There was no difference in achieving full feeds (5 trials; 755 participants; MD: - 0.0 days; 95% CI: - 0.32, 0.31, low certainty) or other outcomes. On subgroup analysis, neonates with birthweight < 1000 g and in the three-hourly feeding regime achieved full enteral feeds slower than those in the two-hourly feeding group (1 trial; 84 participants; MD: 2.9 days, 95% CI: 1.16, 4.64, low certainty)., Conclusion: In stable preterm infants (1000-1500 g), three-hourly feeding can be followed safely. In infants < 1000 g, there is insufficient evidence to advise on an optimal feeding interval, although a 2-h interval might be preferable.Prospero Registration Number: CRD42021246568., What Is Known: • Most of the units follow two-hourly feeding schedules without any evidence. • Recent trials suggest that the three hourly feeding schedules can be safely followed in stable preterm infants., What Is New: • Low certainty evidence suggests that three-hourly feeding is safe in stable preterm infants (1000-1500 grams). • In infants with birthweight <1000 grams, two-hourly feeding may be considered as it was associated with a shorter time to full feeds in subgroup analysis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A considerable proportion of children experience a recurrence of urinary tract infection (UTI) following the first episode. While low-dose antibiotic prophylaxis has been the mainstay for the prevention of UTI, recent evidence raised concerns over their efficacy and safety. Hence, we aim to systematically synthesize evidence on the efficacy and safety of non-antibiotic prophylactic interventions for UTI. Using keywords related to study population (children) and intervention (non-antibiotic), we searched CENTRAL, Embase, PubMed, and Web of Science for randomized controlled trials (RCTs) published until August 2020. RCTs comparing any non-antibiotic interventions with placebo/antibiotics for prevention of UTIs in children were considered eligible. We used a random-effect model to provide pooled estimates. Sixteen trials evaluating 1426 participants were included. Cranberry was as effective as antibiotic prophylaxis (RR: 0.92; 95% CI: 0.56-1.50) but better than placebo/no therapy (RR: 0.48; 95% CI: 0.28-0.80) in reducing UTI recurrence. Probiotic therapy was more effective in reducing UTI recurrence (RR: 0.52; 95% CI: 0.29-0.94) when compared with placebo. While probiotic therapy was not better than antibiotics prophylaxis in preventing UTI (RR: 0.82; 95% CI: 0.56-1.21), they have a lower risk of antibiotic resistance (RR: 0.38; 95% CI: 0.21-0.69).Conclusion: Cranberry products and probiotics are the two non-antibiotic interventions that have been chiefly evaluated, reduce the risk of UTI recurrence when compared with placebo in children with a normal urinary tract. The findings from this systematic review suggest that while cranberry and probiotics may be used, there is a definite need to identify better and more acceptable non-antibiotic interventions. What is Known: • Efficacy of the low-dose antibiotic is controversial in preventing UTI and it is associated with increase in the risk of antimicrobial resistance. • Non-antibiotic interventions such as cranberry products are effective in preventing UTI recurrence in adults. What is New: • Cranberry products are effective in reducing the recurrence of UTI in children with normal urinary tract. • Low-quality evidence suggests that probiotics can be a potential prophylactic measure to reduce recurrence of UTI in the pediatric population., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To conduct a systematic review to provide pooled estimates of the prevalence of hypertension among children aged less than 18 y in India., Methods: Three electronic databases (PubMed, EMBASE, and Web of Science) were searched from inception to August 2020 by using terms related to hypertension, children, prevalence, and India. Studies reporting the prevalence of hypertension, defined based on at least three measurements, were included. Two investigators independently performed the literature search, study selection, and data extraction for this review. Random effect meta-analysis was used to provide pooled estimates of hypertension., Results: A total of 64 studies were included in this systematic review. The pooled prevalence was 7% (95% CI: 6%-8%) for hypertension, 4% (95% CI: 3%-4.1%) for sustained hypertension and 10% (95% CI: 8%-13%) for prehypertension. While there was no significant difference in hypertension across five different regions of the country, an upward rising trend was observed after the year 2005. Urban children had a higher prevalence of hypertension as compared to their rural counterparts. Children with obesity had a significantly high prevalence of hypertension (29%) than normal-weight children (7%)., Conclusion: In this review, it was observed that considerable proportions (7%) of school going children are hypertensive in India. Prevalence was higher in urban and overweight children. This study highlights that hypertension is a public health problem in India; hence, there is a need to implement public health measures to prevent hypertension., (© 2021. Dr. K C Chaudhuri Foundation.)

Despite lack of evidence, the practice of routine prefeed gastric residue aspiration before the next feed is common. Recent studies suggest that this practice might be even harmful. Therefore, we aimed to evaluate the effect of avoiding routine prefeed gastric residue aspiration as compared to routine aspiration, on various clinical outcomes in preterm infants. We searched five different electronic databases (MEDLINE, EMBASE, Web of Science, CINAHL, and Cochrane Library) until March 8, 2021. Only randomized controlled trials comparing the practice of routine prefeed gastric aspiration with no routine aspiration in preterm infants were considered eligible. The random-effects meta-analysis was done using RevMan 5.3 software. Of the 894 unique records identified by our search, we included 6 studies (451 participants) in the review. There was no significant difference in the incidence of necrotizing enterocolitis (RR 0.80; 95% CI 0.31 to 2.08; 421 participants in 5 trials). Avoiding routine prefeed aspiration was associated with achieving full enteral feeds earlier (MD - 3.19 days, 95% CI - 4.22 to - 2.16), shorter duration of hospitalization (MD - 5.32 days; 95% CI - 10.25 to - 0.38), and lower incidence of late-onset sepsis (RR 0.77; 95% CI 0.60 to 0.99). Time to regain birth weight, days of total parenteral nutrition or central venous line usage, culture-positive sepsis, and all-cause mortality did not differ between the two groups.Conclusion: In the absence of other signs of feed intolerance, routine prefeed gastric residue aspiration should be avoided in preterm infants.Prospero registration number: CRD42020197657 What is Known: • Though, routine prefeed aspiration before next feed is a common practice in preterm gavage-fed infants. • Recent study suggests that the omission of routine gastric residual evaluation led to improved weight gain and earlier hospital discharge. What is New: • Low- to moderate-quality evidence suggest that avoiding routine prefeed gastric residue monitoring helps in the reduction of late-onset sepsis, achieving full enteral feeds earlier, and earlier discharge from the hospital. • Abandoning the practice of routine prefeed aspiration in absence of other signs of feed intolerance in preterm low birthweight neonates is safe., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Knowledge about COVID-19 in children is limited due to the paucity of reported data. The pediatric age group comprises only less than 5% of total COVID-19 worldwide, therefore, large studies in this population are unlikely in the immediate future. Hence, we planned to synthesize the current data that will help in a better understanding of COVID-19 in children., Evidence Acquisition: Four different electronic databases (MEDLINE, EMBASE, Web of Science, and CENTRAL) were searched for articles related to COVID-19 in the pediatric population. We included studies reporting disease characteristics and outcomes of COVID-19 in patients aged less than 19 years. We performed a random-effect meta-analysis to provide pooled estimates of various disease characteristics., Results: 27 studies (4857 patients) fulfilling the eligibility criteria were included in this systematic review, from a total of 883 records. About half of the patients had each of fever and cough, 11% (6-17%) had fast breathing, and 6-13% had gastrointestinal manifestations. Most of the patients had mild to moderate disease, and only 4% had a severe or critical illness. Leukopenia was the commonest reported laboratory abnormality., Conclusions: Even among the symptomatic COVID-19 cases, severe manifestations are seen in very few children. Though fever and respiratory symptoms are most common, many children also have gastrointestinal manifestations.

Idiopathic nephrotic syndrome is the most common glomerulopathy in childhood characterised by heavy proteinuria, hypoalbuminemia and edema. Most of the patients have mild and transient edema but those with difficult to treat nephrotic syndrome can develop severe edema which may have serious consequences such as immobility, cellulitis and peritonitis. Understanding of the pathophysiology of edema is still evolving with recent research elucidating newer mechanism of sodium retention through plasmin mediated epithelial sodium channel activation in collecting duct. Patients with mild edema do not require specific diuretic therapy as it improves with steroid induced diuresis. In this review, the authors describe the current perspective in management of moderate to severe edema in childhood nephrotic syndrome including various parameters to assess intravascular volume status which is important for planning overall treatment strategy. Then they briefly discuss about various classes of diuretics, aquaretics and evidence based use of furosemide albumin combination therapy for treatment of edema. Management strategy for a small proportion of patients, who are unresponsive to furosemide therapy, includes diuretic synergism, intravenous furosemide albumin combination therapy and continuous intravenous furosemide infusion.

Aneuploidy can instigate tumorigenesis. However, mutations in genes that control chromosome segregation are rare in human tumors as these mutations reduce cell fitness. Screening experiments indicate that the knockdown of multiple classes of genes that are not directly involved in chromosome segregation can lead to aneuploidy induction. The possible contribution of these genes to cancer formation remains yet to be defined. Here we identified gene knockdowns that lead to an increase in aneuploidy in checkpoint-deficient human cancer cells. Computational analysis revealed that the identified genes overlap with recurrent mutations in human cancers. The knockdown of the three strongest selected candidate genes (ORP3, GJB3, and RXFP1) enhances the malignant transformation of human fibroblasts in culture. Furthermore, the knockout of Orp3 results in an aberrant expansion of lymphoid progenitor cells and a high penetrance formation of chromosomal instable, pauci-clonal B-cell lymphoma in aging mice. At pre-tumorous stages, lymphoid cells from the animals exhibit deregulated phospholipid metabolism and an aberrant induction of proliferation regulating pathways associating with increased aneuploidy in hematopoietic progenitor cells. Together, these results support the concept that aneuploidy-inducing gene deficiencies contribute to cellular transformation and carcinogenesis involving the deregulation of various molecular processes such as lipid metabolism, proliferation, and cell survival.

Energy stress depletes ATP and induces cell death. Here we identify an unexpected inhibitory role of energy stress on ferroptosis, a form of regulated cell death induced by iron-dependent lipid peroxidation. We found that ferroptotic cell death and lipid peroxidation can be inhibited by treatments that induce or mimic energy stress. Inactivation of AMP-activated protein kinase (AMPK), a sensor of cellular energy status, largely abolishes the protective effects of energy stress on ferroptosis in vitro and on ferroptosis-associated renal ischaemia-reperfusion injury in vivo. Cancer cells with high basal AMPK activation are resistant to ferroptosis and AMPK inactivation sensitizes these cells to ferroptosis. Functional and lipidomic analyses further link AMPK regulation of ferroptosis to AMPK-mediated phosphorylation of acetyl-CoA carboxylase and polyunsaturated fatty acid biosynthesis. Our study demonstrates that energy stress inhibits ferroptosis partly through AMPK and reveals an unexpected coupling between ferroptosis and AMPK-mediated energy-stress signalling.

Galloway-Mowat syndrome (GAMOS) is a phenotypically heterogeneous disorder characterized by neurodevelopmental defects combined with renal-glomerular disease, manifesting with proteinuria. To identify additional monogenic disease causes, we here performed whole exome sequencing (WES), linkage analysis, and homozygosity mapping in three affected siblings of an Indian family with GAMOS. Applying established criteria for variant filtering, we identify a novel homozygous splice site mutation in the gene WDR4 as the likely disease-causing mutation in this family. In line with previous reports, we observe growth deficiency, microcephaly, developmental delay, and intellectual disability as phenotypic features resulting from WDR4 mutations. However, the newly identified allele additionally gives rise to proteinuria and nephrotic syndrome, a phenotype that was never reported in patients with WDR4 mutations. Our data thus expand the phenotypic spectrum of WDR4 mutations by demonstrating that, depending on the specific mutated allele, a renal phenotype may be present. This finding suggests that GAMOS may occupy a phenotypic spectrum with other microcephalic diseases. Furthermore, WDR4 is an additional example of a gene that encodes a tRNA modifying enzyme and gives rise to GAMOS, if mutated. Our findings thereby support the recent observation that, like neurons, podocytes of the renal glomerulus are particularly vulnerable to cellular defects resulting from altered tRNA modifications., (© 2018 Wiley Periodicals, Inc.)

Telomeres form protective caps at the ends of linear chromosomes to prevent nucleolytic degradation, end-to-end fusion, irregular recombination, and chromosomal instability. Telomeres are composed of repetitive DNA sequences (TTAGGG)n in humans, that are bound by specialized telomere binding proteins. Telomeres lose capping function in response to telomere shortening, which occurs during each division of cells that lack telomerase activity-the enzyme that can synthesize telomeres de novo. Telomeres have a dual role in cancer: telomere shortening can lead to induction of chromosomal instability and to the initiation of tumors, however, initiated tumors need to reactivate telomerase in order to stabilize chromosomes and to gain immortal growth capacity. In this review, we summarize current knowledge on the role of telomeres in the maintenance of chromosomal stability and carcinogenesis.