To develop a minimally invasive preventive measure for early osteoarthritis, the effect of melatonin on cartilage matrix synthesis of articular chondrocytes was evaluated in vitro in a pellet culture system. The chondrogenic markers were assessed using histology, TaqMan polymerase chain reaction, and western blot. Our results show that melatonin treatment yielded chondrocyte-pellets with a higher expression of chondrogenic markers consisting of collagen II, Sox 9, and aggrecan at both the mRNA and protein levels. A hypertrophic marker, collagen X, remained low. Moreover, up-regulation of internal transforming growth factor beta1 (TGF-beta1) expression was observed in the melatonin-treated cells. Our data indicate, for the first time, that the administration of melatonin enhances cartilage matrix synthesis of articular chondrocytes in a serum-containing pellet culture system, likely through the TGF-beta signal pathway. Melatonin may prove to be a highly valuable addition to current therapeutic models for degenerative cartilage repair.

Coronavirus disease 2019 (COVID‐19) is a highly infectious disease caused by the severe acute respiratory syndrome coronavirus 2 virus (SARS‐CoV‐2). While children appear to experience less severe disease than adults, those with underlying conditions such as kidney disease may be more susceptible to infection. Limited data are present for children with kidney disease, and there are limited prior reports of pediatric hemodialysis patients with COVID‐19. This report describes the mild clinical disease course of COVID‐19 in two pediatric patients with chronic kidney disease, one on hemodialysis and both on chronic immunosuppression. We review treatment in these patients, as well as our measures to reduce transmission among our hemodialysis patients and staff.

Wendell L. Hughes was a pioneer in ophthalmic plastic surgery and best known for the "Hughes flap," a tarsoconjunctival flap used for lower eyelid reconstruction. In 1937, Wendell L. Hughes sought to achieve the criterion standard of replacing "like with like" in his development of the tarsoconjunctival flap for lower lid reconstruction. This work was published in his ground-breaking thesis, Reconstructive Surgery of the Eyelids, the most comprehensive book on ophthalmic plastic surgery of its time. Although this flap has undergone many modifications, it has stood the test of time and is still used today. In addition, Dr. Hughes was heavily involved in surgical education, a founding member of the American Board of Plastic Surgery, and a leader in the development of sutures and microneedles. More importantly, he was a gracious humanitarian and inspiring mentor loved by peers and patients alike. Other authors have reviewed the intricacies of the Hughes flap; however, little attention has been given to the contributions of its creator.

Dear Editor, We identify that children with a history of urinary tract infections (UTIs) and vesicoureteral reflux (VUR) with low deleted in Malignant Brain Tumors 1 (DMBT1) DNA copy number have ∼4-fold higher odds of recurrent UTIs compared to those with high DMBT1 DNA copy number. With bacterial resistance to antibiotics increasing, we need to develop new strategies to guide judicious use of antibiotics such as using the patient's genetic profile. 1 Some groups, such as children with VUR, are at risk for UTIs and associated adverse outcomes. The Randomized Intervention for Children with VUR (RIVUR) study determined that antibiotic prophylaxis reduced recurrent UTIs in children with VUR but at the expense of increased resistance. 2 In a genome-wide array, we identified that DMBT1 locus was a candidate gene for genetic variation in the UTI/VUR patient population. 3 We have also shown that DMBT1 has two copy number variations which occur in scavenger receptor cysteine-rich domains (SRCR) which have bacterial agglutination capabilities. 4,5 The first CNV involves SRCR3-SRCR6 and is called DMBT1 CNV SRCR3-6 ; the other involves SRCR9-SRCR11 and is called DMBT1 CNV SRCR9-11 (Supplemental Material S1). 4 We used paralogue ratio testing to determine the absolute DMBT1 copy number in RIVUR patients. We also evaluated the biological relevance of DMBT1 in experimental UTI models of a knockout mouse (Dmbt1 −/− ). 6 Agglutination studies of uropathogenic Escherichia coli (UPEC) with recombinant DMBT1 6 kb (DMBT1 gp340 -short) or recombinant DMBT1 8 kb (DMBT1 gp340 -long) as surrogate model for the protein produced by low and high DMBT1 copy number respectively were also performed. 7 Full details about the methods may be found in Supplemental Material S2.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Nephrogenic diabetes insipidus (NDI), a rare cause of polyuria and polydipsia in children, is usually managed with medications and careful monitoring of water intake. We present a child who was incidentally found to have right hydronephrosis secondary to ureteropelvic junction obstruction, and was subsequently also diagnosed with NDI. After being medically managed, he underwent open right pyeloplasty. His polydipsia abated within 1 month of surgery, and he has done well off of medications since that time. NDI resolution after correction of obstructive uropathy in adults has been reported, but this represents a novel case in pediatrics.

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Background: Uropathogenic Escherichia coli (UPEC) infections are common and when they disseminate can be of high morbidity. Methods: We studied the effects of UPEC infection using single cell RNA sequencing (scRNAseq) in zebrafish. Bulk RNA sequencing has historically been used to evaluate gene expression patterns, but scRNAseq allows gene expression to be evaluated at the single cell level and is optimal for evaluating heterogeneity within cell types and rare cell types. Zebrafish cohorts were injected with either saline or UPEC,and scRNAseq and canonical pathway analyses were performed. Results: Canonical pathway analysis of scRNAseq data provided key information regarding innate immune pathways in the cells determined to be thymus cells, ionocytes, macrophages/monocytes, and pronephros cells. Pathways activated in thymus cells included interleukin 6 (IL-6) signaling and production of reactive oxygen species. Fc receptor-mediated phagocytosis was a leading canonical pathway in the pronephros and macrophages. Genes that were downregulated in UPEC vs saline exposed embryos involved the cellular response to the Gram-negative endotoxin lipopolysaccharide (LPS) and included Forkhead Box O1a (Foxo1a), Tribbles Pseudokinase 3 (Trib3), Arginase 2 (Arg2) and Polo Like Kinase 3 (Plk3). Conclusions: Because 4-day post fertilization zebrafish embryos only have innate immune systems, the scRNAseq provides insights into pathways and genes that cell types utilize in the bacterial response. Based on our analysis, we have identified genes and pathways that might serve as genetic targets for treatment and further investigation in UPEC infections at the single cell level.