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94). Finally, children with clinically low BMD z scores were found to have higher alanine aminotransferase (P<.05) and gamma-glutamyl transferase (P<.05) levels compared with children with normal BMD z scores.

Across the full range of liver MRI-PDFF, there was a strong negative relationship between hepatic steatosis and BMD z score. Given the prevalence of nonalcoholic fatty liver disease and the critical importance of childhood bone mineralization in protecting against osteoporosis, clinicians should prioritize supporting bone development in children with nonalcoholic fatty liver disease.

Across the full range of liver MRI-PDFF, there was a strong negative relationship between hepatic steatosis and BMD z score. Given the prevalence of nonalcoholic fatty liver disease and the critical importance of childhood bone mineralization in protecting against osteoporosis, clinicians should prioritize supporting bone development in children with nonalcoholic fatty liver disease.

To provide a comprehensive assessment of case stratification by the Neonatal Early-Onset Sepsis (EOS) Calculator, a novel tool for reducing unnecessary antibiotic treatment.

A systematic review with individual patient data meta-analysis was conducted, extending PROSPERO record CRD42018116188. Cochrane, PubMed/MEDLINE, EMBASE, Web of Science, Google Scholar, and major conference proceedings were searched from 2011 through May 1, 2020. Original data studies including culture-proven EOS case(s) with EOS Calculator application, independent from EOS Calculator development, and including representative birth cohorts were included. Relevant (individual patient) data were extracted from full-text and data queries. The main outcomes were the proportions of EOS cases assigned to risk categories by the EOS Calculator at initial assessment and within 12hours. Evidence quality was assessed using Newcastle-Ottawa scale, Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies, and GRADE tools.

Among 543 unique search results, 18 were included, totaling more than 459 000 newborns. Among 234 EOS cases, EOS Calculator application resulted in initial assignments to (strong consideration of) empiric antibiotic administration for 95 (40.6%; 95% CI, 34.2%-47.2%), more frequent vital signs for 36 (15.4%; 95% CI, 11.0%-20.7%), and routine care for 103 (44.0%; 95% CI, 37.6%-50.6%). Bcl-xL protein By 12hours of age, these proportions changed to 143 (61.1%; 95% CI, 54.5%-67.4%), 26 (11.1%; 95% CI, 7.4%-15.9%), and 65 (27.8%; 95% CI, 22.1%-34.0%) of 234 EOS cases, respectively.

EOS Calculator application assigns frequent vital signs or routine care to a substantial proportion of EOS cases. Clinical vigilance remains essential for all newborns.

EOS Calculator application assigns frequent vital signs or routine care to a substantial proportion of EOS cases. Clinical vigilance remains essential for all newborns.

To describe longitudinal health care utilization of Medicaid-insured children with a history of neonatal abstinence syndrome (NAS) compared with similar children without NAS.

Retrospective, longitudinal cohort study. Data were extracted from the Medicaid Analytic eXtract files for all available states and DC from 2003-2013. Subjects were followed up to 11years. In total, 17 229 children with NAS were identified using the International Classification of Diseases, Ninth Revision code 779.5. Children without NAS, matched on demographic and health variables, served as the comparison group. Outcomes were number of claims for inpatient, outpatient, and emergency department encounters, numbers of prescription claims, and costs associated with these services. Linked claims were identified for each subject using a unique, within-state ID.

Children with NAS had increased claims for inpatient admissions (marginal effect [ME] 0.49; SE 0.01) and emergency department visits (ME 0.30; SE 0.04) through year 1; increaserelevant diagnoses in a health care database.Inouye et al. (2020) use the observation that Ser is coded in the genetic code by two blocks of codons that differ on more than one base to understand some aspects of the origin of the genetic code organization. I argue instead that this observation per se cannot be used to understand any aspect of the origin of the genetic code, unless it is accompanied by other assumptions concerning in the specific case (i) the ancestrality of some amino acids, (ii) the hypothesis that the first mRNA to be translated was poly-G, which can be translated into poly-Gly, and (iii) an evolutionary mechanism for the genetic code origin based on the duplication of tRNAs. However, both the tRNA duplication mechanism and the existence of poly-G as the first mRNA to be translated are not corroborated as mechanisms through which the genetic code would have been structured. For example, the origin of the actual mRNA should have been preceded by the evolution of a proto-mRNA which evidently already coded for more than one amino acid. Therefore, when it evolved from proto-mRNA, the mRNA should already have coded for more than one amino acid. In other words, poly-G as mRNA would most likely never have existed because the first mRNAs already had to code for more than one amino acid. On the contrary, all these assumptions would have been operational if the observations of Inouye et al. (2020) had been discussed within the coevolution theory of the origin of the genetic code, which they do not.Proximal tubule epithelial cells (PTEC) are susceptible to drug-induced kidney injury (DIKI). Cell-based, two-dimensional (2D) in vitro PTEC models are often poor predictors of DIKI, probably due to the lack of physiological architecture and flow. Here, we assessed a high throughput, 3D microfluidic platform (Nephroscreen) for the detection of DIKI in pharmaceutical development. This system was established with four model nephrotoxic drugs (cisplatin, tenofovir, tobramycin and cyclosporin A) and tested with eight pharmaceutical compounds. Measured parameters included cell viability, release of lactate dehydrogenase (LDH) and N-acetyl-β-d-glucosaminidase (NAG), barrier integrity, release of specific miRNAs, and gene expression of toxicity markers. Drug-transporter interactions for P-gp and MRP2/4 were also determined. The most predictive read outs for DIKI were a combination of cell viability, LDH and miRNA release. In conclusion, Nephroscreen detected DIKI in a robust manner, is compatible with automated pipetting, proved to be amenable to long-term experiments, and was easily transferred between laboratories.

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