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Purpose: The purpose of this study was to determine factors significantly associated with mortality and length of stay (LOS) in admissions to the pediatric intensive care unit (PICU) for traumatic brain injury (TBI). Methods: A cross-sectional, retrospective cohort study that identified PICU admissions with TBI from forty-nine hospitals in the USA using the Pediatric Health Information System database from 2016 to 2021. Univariable analyses comparing those who did and did not experience mortality were performed. The following regression analyses were conducted: logistic regression with mortality as dependent variable; linear regression with LOS as the dependent variable; logistic regression with mortality as the dependent variable but only included patients with cerebral edema; and linear regression with LOS as the dependent variable but only included patients who survived. From the regression analysis for mortality in all TBI patients was utilized to develop a mortality risk score. Results: A total of 3041 admissions were included. Those with inpatient mortality (18.5%) tended to be significantly younger (54 vs. 92 months, p < 0.01), have < 9 pediatric Glasgow Coma Scale on admission (100% vs. 52.9%, p < 0.01) and more likely to experience acute renal, hepatic and respiratory failure, acidosis, central diabetes insipidus, hyperkalemia, and hypocalcemia. Regression analysis identified that pediatric Glasgow Coma Scale, alkalosis and cardiac arrest significantly increased risks of mortality. The TBI mortality risk score had an area under the curve of 0.89 to identify those with mortality; a score of 6 ≤ was associated with 88% mortality. Conclusion: Patients admitted to the PICU with TBI have 18.5% risk of inpatient mortality with most occurring the first 48 h and these are characterized with greater multisystem organ dysfunction, received medical and mechanical support. TBI mortality risk score suggested is a practical tool to identify patients with an increase likelihood to die. [ABSTRACT FROM AUTHOR]

Carnitine is an essential amino acid involved in transporting fatty acids across the mitochondrial membrane. Fatty acids are a primary source of energy for the myocardium. Studies in adults demonstrated decreased carnitine levels in the ischemic myocardium, but subsequent exogenous carnitine supplementation showed improvement of myocardial metabolism and left ventricular function. However, only limited data regarding carnitine are available in pediatrics. A single-center retrospective, paired data study was conducted. Patients < 18 years, left ventricular ejection fraction (LVEF) < 55% by echocardiography, and had received at least 7 days of oral or intravenous carnitine supplementation between January 2018 and March 2021 are included in the study. Several endpoints and covariates were collected for each patient: before, one week after, one month after, and 6 months after carnitine supplementation. Univariate analysis consisted of an analysis of variance (ANOVA), followed by an analysis of covariance (ANCOVA) to model LVEF while adjusting for other variables. 44 patients included in the final analyses. LVEF significantly improved from 50.5 to 56.6% (p < 0.01). When LVEF was adjusted for other interventions (mechanical ventilation, afterload reduction, diuretic therapy, spironolactone), the estimated means demonstrated a significant increase from 45.7 to 58.0% (p < 0.01). Free carnitine level increased significantly (p = 0.03), and N-terminal-pro-brain natriuretic peptide (p = 0.03), creatinine (p < 0.01), and lactate (p < 0.01) all significantly decreased over the study period. Carnitine supplementation in pediatric patients with left ventricular systolic dysfunction may be associated with an increase in LVEF and improvement in laboratory markers of myocardial stress and cardiac output. [ABSTRACT FROM AUTHOR]

Sample size and statistical power are often limited in pediatric cardiology studies due to the relative infrequency of specific congenital malformations of the heart and specific circulatory physiologies. The primary aim of this study was to determine what proportion of pediatric cardiology randomized controlled trials achieve an 80% statistical power. Secondary aims included characterizing reporting habits in these studies. A systematic review was performed to identify pertinent pediatric cardiology randomized controlled trials. The following data were collected: publication year, journal, if "power" or "sample size" were mentioned if a discrete, primary endpoint was identified. Power analyses were conducted to assess if the sample size was adequate to demonstrate results at 80% power with a p-value of less than 0.05. A total of 83 pediatric cardiology randomized controlled trials were included. Of these studies, 48% mentioned "power" or "sample size" in the methods, 49% mentioned either in the results, 12% mentioned either in the discussion, and 66% mentioned either at any point in the manuscript. 63% defined a discrete, primary endpoint. 38 studies (45%) had an adequate sample size to demonstrate differences with 80% power at a p-value of less than 0.05. A majority of these are not powered to reach the conventionally accepted 80% power target. Adequately powered studies were found to be more likely to report "power" or "sample size" and have a discrete, primary endpoint. [ABSTRACT FROM AUTHOR]

Fluid overload is associated with increased morbidity and mortality after pediatric cardiac surgery. Management of fluid overload can be difficult and conventional tools may increase the risk of acute kidney injury. This study aimed to study the effects of aminophylline on fluid balance, urine output, blood urea nitrogen, and serum creatinine. Pediatric cardiac surgical patients who received aminophylline between September 2022 and December 2023 were identified. Data for various clinical parameters before and after an aminophylline dose were collected. Paired univariable analyses and a random forest classifier were conducted to help characterize the effects of aminophylline. A total of 169 aminophylline administrations in 72 unique patients were included in the final analyses. Fluid balance decreased by 115% in the 24 h after aminophylline administration compared to the 24 h preceding. Urine output peaked at 2 h after administration and increased 100% from baseline. Heart rate increased by 5% after administration and peaked between 2 and 4 h after. In pediatric patients after cardiac surgery, a 5 mg/kg dose of aminophylline is safe and is associated with a reduction in fluid balance and increase in urine output without significantly changing blood urea nitrogen or serum creatinine levels. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a progressive movement disorder characterized by degeneration of the substantia nigra pars compacta. Physical therapy (PT) is effective for managing symptoms of PD, but there are limiting factors to the PT episode of care. The purpose of this systematic review is to analyze the effects and neurobiology of supplemental activities such as dance, yoga, and martial arts on motor and non-motor symptoms of PD. Database searches were utilized to identify evidence, followed by PEDro scoring. Here, 35 articles were analyzed, and 25 articles were included for review of current data regarding nontraditional movement interventions for PD. We conclude that supplemental activities are effective for significantly improving motor and nonmotor symptoms of PD. These findings are particularly useful for dance/movement therapists working with the Parkinson's population and with the older adult population. [ABSTRACT FROM AUTHOR]

Objective: To compare the predictive value of the IAP and WHO criteria in identifying obesity complications in Indian children and adolescents. Methods: Blood pressure and body mass index was measured in 4434 children and adolescents [2539 boys; mean age 11.9 (3.0), 5.1–18 y] from affluent schools. The predictive accuracy of IAP 2015 and WHO BMI criteria in identifying hypertension was assessed. Results: IAP 2015 BMI criteria labelled 203 more children obese than the WHO reference (649 as against 446). Hypertension was present in 75 (37%) of these. The difference in the prevalence of hypertension in subjects obese as per IAP 2015 criteria and their nonobese counterparts (50.2% as against 10.8%, p < 0.0001) was greater than that between subjects obese only by IAP 2015 or by both the criteria (36.9% as against 56.3%, p < 0.0001). The difference in the proportion of subjects with hypertension between two consecutive IAP 2015 BMI SDS category was highest for + 1.5 in boys (32.3% as against 49.8%, p < 0.0001) and + 2 in girls (25.9% as against 59.3%, p < 0.00012). Conclusion: IAP BMI criteria better predict hypertension in Indian children than WHO cutoffs and should be used in clinical practice to predict obesity complications. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate a mobile application–based tool for the management guidance of children and adolescents with diabetic ketoacidosis (DKA). Methods: The study involved the development of a mobile application–based tool for DKA management in accordance with the International Society of Pediatric and Adolescent Diabetes (ISAPD) guidelines, 2018. The impact of the mobile application in preventing protocol deviation and resultant complications was assessed. Case records of 70 children and adolescents [39 boys, 8.9 (4.1) y of age] with severe DKA managed in the authors' intensive care unit were examined. The application guidance and real-time management were compared to the standard protocol. Results: Protocol deviations were observed in 58 (82.9%), with two or more errors in 28 (40%). These included lack of initial fluid bolus (4, 5.7%), excessive fluid supplementation (8, 11.4%), inadequate initial fluid (25, 35.7%) and potassium supplementation (13, 18.6%), delayed response to fall in potassium (15, 21.4%) and glucose levels (24, 34.3%), and erroneous insulin administration (19, 27.1%). These errors contributed to 42.1% of severe hypokalemia and 56% of significant hypoglycemia episodes. The mobile application guidance was in accordance with the protocol in all the case scenario. Conclusion: Deviation from the management protocol is common in DKA and associated with adverse outcomes. Mobile application guidance is expected to reduce the protocol deviation with a potential of improving outcomes. [ABSTRACT FROM AUTHOR]

Objective: To study determinants and predictors of body fat in Indian children and adolescents.Methods: In this cross-sectional study, 5175 children and adolescents [3014 boys, age 12.8 (3) y, 5-18 y] participated. Determinants and predictors of body fat were assessed using partial correlation (corrected for age, and gender) and linear regression.Results: Fat percentage correlated negatively with the duration of physical activity (r = -0.091, p < 0.01) and sleep (r = -0.044, p = 0.01) and positively with parental body mass index (BMI) (r = 0.202, p < 0.01 for father and r = 0.235, p < 0.01 for mother), and birth weight (r = 0.050, p < 0.01). On linear regression, fat percentage was positively associated with parental BMI and birth weight, and negatively with physical activity and sleep duration. All adiposity markers [BMI standard deviation score (SDS) (r = 0.863, p < 0.01), weight SDS (r = 0.827, p < 0.01) waist to height ratio (r = 0.819, p < 0.01), waist circumference SDS (r = 0.765, p < 0.01) wrist circumference (r = 0.21, p < 0.01), and neck circumference (r = 0.19, p < 0.01)] correlated significantly with fat percentage, showing highest correlation with BMI SDS.Conclusion: Reduced sleep and physical activity are the key modifiable risk factors for adiposity. BMI SDS is the best clinical surrogate of body fat in Indian children and adolescents. There is a need to explore the impact of lifestyle interventions targeting sleep and physical activity on adiposity. [ABSTRACT FROM AUTHOR]

Packed red blood cell (PRBC) transfusions are commonly administered in pediatric patients following the Norwood operation. This study was conducted to determine the effect of PRBC transfusions on hemodynamic parameters in pediatric patients with single-ventricle physiology and parallel circulation. A single-center, retrospective chart review was conducted. Pediatric patients admitted to the cardiac intensive care unit after Norwood operation between 2017 and 2018 were identified. Hemodynamic parameters were collected within a four-hour period before and after a PRBC transfusion. Univariate analyses using paired t tests were conducted to compare blood gas values before and after PRBC transfusion. Next, multivariate regression analyses were conducted to model the impact of transfusion volume, change in hemoglobin levels, and change in FiO2 on the change in PaO2 and PaCO2. These analyses included data from 33 eligible patients who received a PRBC transfusion following a Norwood operation. The hemoglobin levels (p < 0.01) and the PaO2/FiO2 ratio (p = 0.04) were significantly increased, while arterial lactate levels (p = 0.03) were significantly decreased following the transfusion. Transfusion for a pre-transfusion hemoglobin of 12.4 g/dL appears to provide greatest reduction in lactate, used as a surrogate marker for systemic oxygen delivery. No significant changes were found in arterial pH, PaO2, and PaCO2. PRBC transfusions following the Norwood operation may be a useful intervention to increase systemic oxygen delivery, improving PaO2/FiO2 ratio and improving serum lactate. The benefits of PRBC transfusions must be weighed against previously identified risks on a patient-specific basis. Further studies are warranted to further delineate the effects of such transfusions in this population. [ABSTRACT FROM AUTHOR]

Short stature is a common presentation to pediatricians with a significant overlap between physiology and pathology. Thus, while most short children have a physiological cause, growth failure may be the only manifestation of severe underlying disease. Growth failure evaluation aims to avoid unnecessary investigations in children with a physiological cause without missing pathology. Guidelines for the evaluation of short stature allow stepwise evaluation but are limited by their resource-intense nature. An objective application of anthropometric indices and careful clinical evaluation allows rational growth failure workup. The use of height standard deviation score (SDS) for determining the need for evaluation (no evaluation above −2, follow-up between −2 to −3, and immediate workup with height below −3), corrected height SDS to identify familial short stature (above −1.5), height SDS for bone age for constitutional delay of puberty and growth (above −2), and BMI SDS for nutritional pattern growth failure (below −1) helps reduce the burden of investigations. The present review provides a framework for comprehensive growth evaluation across resource levels and settings. [ABSTRACT FROM AUTHOR]

Objective: Subclinical hypothyroidism is common in children and adolescents with obesity and has been considered to be its effect with no need for treatment. Its metabolic impact has not been evaluated. Therefore the present study was conducted to determine the metabolic impact of obesity related subclinical hypothyroidism.Methods: Retrospective record review of obese children and adolescents between 5 and 18 y of age presenting to pediatric endocrine clinic was done. Four hundred four obese children and adolescents [251 boys, 11.8 (3.2); 5.1-18 y, BMI SDS 2.4 (0.7); 1.4-6.6] were assessed regarding thyroid functions, adiposity (clinical and DXA derived) and metabolic complications.Results: Subclinical hypothyroidism was observed in 122 (30.2%) and was associated with higher fat percentage [49.2 (5.8) vs. 47.2 (6.4) p = 0.009], android to gynoid ratio [1.1 (0.1) vs. 1.0 (0.1), p = 0.007] and alanine aminotransferase (ALT) levels [49.3 (31.5) vs. 40.8 (38.1), p = 0.04]. Subjects with subclinical hypothyroidism had 1.9 times greater odds of having non-alcoholic steatohepatitis (47.3% vs. 31.8%, p = 0.005) with no difference in the prevalence of dyslipidemia, dysglycemia or hypertension. Subclinical hypothyroidism was the only determinant of non-alcoholic steatohepatitis on binomial logistic regression (WALD = 11.04, p = 0.001) with no impact of BMI SDS, waist circumference SDS, fat percentage or android to gynoid ratio. Thyroid stimulating hormone (TSH) was the most important determinant of ALT on linear regression (B = 3.027, p < 0.005).Conclusions: Obesity related subclinical hypothyroidism predisposes to increased ALT and non-alcoholic steatohepatitis independent of severity adiposity. The impact of thyroid supplementation in this setting needs to be explored. [ABSTRACT FROM AUTHOR]

Objective: To compare the diagnostic accuracy of IAP 2015, WHO and IAP 2007 growth charts in identifying pathological short stature in Indian children. Methodology: The predictive value of the growth charts for pathological short stature was assessed in 500 (266 boys) short subjects (age 5–17.9 years) presenting to our pediatric endocrine clinic. Results: WHO, IAP 2015, IAP 2007 criteria classified 500, 410 (82%) and 331 (66.2%) subjects short respectively. A total of 218 (43.6%) subjects had a pathological cause. Two out of 90 subjects short by WHO criteria but normal as per IAP 2015 had a pathological cause (2.2%) whereas 38 out of 79 subjects short as per WHO and IAP 2015 criteria but normal by IAP 2007 had pathological short stature. The diagnostic measures of IAP 2015 and IAP 2007 charts in identifying pathological short stature showed a sensitivity 99.1% and 81.7%, negative predictive value 97.8% as against 76.3%, positive predictive value 52.7% and 53.8%, and specificity of 31.2% and 45.7%, respectively. Conclusions: IAP 2015 growth charts are superior in identifying pathological growth failure compared to WHO and IAP 2007. [ABSTRACT FROM AUTHOR]

However, as the authors were aware, several other endpoints were included to analyze the issue of "power" in pediatric cardiology randomized controlled trials in our study. Author Contributions RSL wrote the first draft of the text, and SF edited the draft. We present data for these other endpoints to demonstrate the overall treatment of "power" and "sample size" by these trials which were mentioned in various parts of the manuscript, as well as the lack of a basic definition of a primary endpoint to even perform a power calculation. [Extracted from the article]

Nodal-related protein (ndr2) is a member of the transforming growth factor type β superfamily of factors and is required for ventral midline patterning of the embryonic central nervous system in zebrafish. In humans, mutations in the gene encoding nodal cause holoprosencephaly and heterotaxy. Mutations in the ndr2 gene in the zebrafish (Danio rerio) lead to similar phenotypes, including loss of the medial floor plate, severe deficits in ventral forebrain development and cyclopia. Alleles of the ndr2 gene have been useful in studying patterning of ventral structures of the central nervous system. Fifteen different ndr2 alleles have been reported in zebrafish, of which eight were generated using chemical mutagenesis, four were radiation-induced and the remaining alleles were obtained via random insertion, gene targeting (TALEN) or unknown methods. Therefore, most mutation sites were random and could not be predicted a priori. Using the CRISPR-Cas9 system from Streptococcus pyogenes, we targeted distinct regions in all three exons of zebrafish ndr2 and observed cyclopia in the injected (G0) embryos. We show that the use of sgRNA-Cas9 ribonucleoprotein (RNP) complexes can cause penetrant cyclopic phenotypes in injected (G0) embryos. Targeted polymerase chain reaction amplicon analysis using Sanger sequencing showed that most of the alleles had small indels resulting in frameshifts. The sequence information correlates with the loss of ndr2 activity. In this study, we validate multiple CRISPR targets using an in vitro nuclease assay and in vivo analysis using embryos. We describe one specific mutant allele resulting in the loss of conserved terminal cysteine-coding sequences. This study is another demonstration of the utility of the CRISPR-Cas9 system in generating domain-specific mutations and provides further insights into the structure-function of the ndr2 gene. [ABSTRACT FROM AUTHOR]

The flat-headed cat ( Prionailurus planiceps) is a wetland specialist, currently facing habitat loss on a serious scale due to massive destruction of lowland forests and wetlands in Southeast Asia. Despite its 'endangered' status in the IUCN Red List, there has virtually been no investigation on the population structure nor on the evolutionary history of the flat-headed cat. To fill this gap, we used full mitochondrial genome sequences, obtained from archival samples, covering the historical distribution of the flat-headed cat. Our data revealed a high genetic differentiation ( F = 0.81, P < 0.001) between mitochondrial lineages from Borneo and those from Thai-Malay Peninsula/Sumatra, a split that was dated to ~575 Kya. Such a significant differentiation clearly distinguishes the Bornean flat-headed cat population from all other populations and suggests that there should be a reassessment of the flat-headed cat's intraspecific taxonomy. However, morphological and nuclear data are required to corroborate our mtDNA results. Until such data become available, we recommend that for future conservation efforts and captive breeding programmes the two genetically distinct flat-headed cat populations are managed separately as two lineages to maintain the original genetic diversity of this endangered species. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common non-skin cancer in the world. Tobacco chewing is implicated with most of the cases of HNSCC but this type of cancer is increasing in non-tobacco chewers as well. This study was instigated to provide comprehensive variant and gene-level data in HNSCC subjects of the Indian population and fill the gap in the literature on comparative assessment of gene mutations in cancer subjects with a habit of tobacco and those without any habit using targeted amplicon sequencing. We performed targeted Amplicon sequencing of 409 tumor suppressor genes and oncogenes, frequently mutated across many cancer types, including head and neck. DNA from primary tumor tissues and matched blood was analyzed for HNSCC patients with a habit of tobacco and those without any habit. PDE4DIP, SYNE1, and NOTCH1 emerged as the highly mutated genes in HNSCC. A total of 39 candidate causal variants in 22 unique cancer driver genes were identified in non-habitual (WoH) and habitual (WH) subjects. Comparison of genes from both the subjects, showed seven unique cancer driver genes (KIT, ATM, RNF213, GATA2, DST, RET, CYP2C19) in WoH, while WH showed five (IL7R, PKHD1, MLL3, PTPRD, MAPK8) and 10 genes (SETD2, ATR, CDKN2A, NCOA4, TP53, SYNE1, KAT6B, THBS1, PTPRT, and FGFR3) were common to both subjects. In addition to this NOTCH1, NOTCH2, and NOTCH4 gene were found to be mutated only in habitual subjects. These findings strongly support a causal role for tobacco, acting via PI3K and MAPK pathway inhibition and stimulation of various genes leading to oncogenic transformations in case of tobacco chewers. In case of non-tobacco chewers it appears that mutations in the pathway affecting the squamous epithelial lineage and DNA repair genes lead to HNSCC. Somatic mutation in CYP2C19 gene in the non-habitual subjects suggests that this gene may have a tobacco independent role in development and progression of HNSCC. In addition to sharing high mutation rate, NOTCH gene family was found to be mutated only in habitual sample. Further, presence of mutated genes not earlier reported to be involved in HNSCC, suggest that the Indian sub-continent may have different sets of genes, as compared to other parts of the world, involved in the development and progression of HNSCC. [ABSTRACT FROM AUTHOR]

Present study attempts in revealing taxonomic and functional diversity of microorganism from petroleum muck using metagenomics approach. Using Ion Torrent Personal Genome Machine, total of 249 Mb raw data were obtained which was analysed using MG-RAST platform. The taxonomic analysis revealed predominance of Proteobacteria with Gammaproteobacteria as major class and Pseudomonas stutzeri as most abundant organism. Several enzymes involved in aliphatic and aromatic hydrocarbon degradation through both aerobic and anaerobic routes and proteins related to stress response were also present. Comparison of our metagenome with the existing metagenomes from oil-contaminated sites and wastewater treatment plant indicated uniqueness of this metagenome taxonomically and functionally. Based on these results a hypothetical community model showing survival and syntrophy of microorganisms in hydrocarbon-rich environment is proposed. Validation of the metagenome data was done in three tiers by validating major OTUs by isolating oil-degrading microbes, confirmation of key genes responsible for hydrocarbon degradation by Sanger sequencing and studying functional dynamics for degradation of the hydrocarbons by the muck meta-community using GC-MS. [ABSTRACT FROM AUTHOR]