RESUMO
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.
Assuntos
Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação a DNA/genética , Proteínas Supressoras de Tumor/genética , Infecções Urinárias/patologia , Animais , Antibacterianos/uso terapêutico , Proteínas de Ligação ao Cálcio/deficiência , Estudos de Casos e Controles , Criança , Variações do Número de Cópias de DNA , Proteínas de Ligação a DNA/deficiência , Modelos Animais de Doenças , Predisposição Genética para Doença , Humanos , Camundongos , Camundongos Knockout , Fatores de Risco , Proteínas Supressoras de Tumor/deficiência , Sistema Urinário/metabolismo , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/genéticaRESUMO
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.
Assuntos
COVID-19/terapia , Terapia de Imunossupressão , Diálise Renal , Insuficiência Renal Crônica/complicações , SARS-CoV-2 , Adolescente , COVID-19/prevenção & controle , Criança , Humanos , Masculino , Insuficiência Renal Crônica/terapiaRESUMO
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.
Assuntos
Diabetes Insípido Nefrogênico/complicações , Obstrução Ureteral/complicações , Obstrução Ureteral/cirurgia , Humanos , Hidronefrose/etiologia , Lactente , Pelve Renal/cirurgia , Masculino , Polidipsia/etiologia , Poliúria/etiologiaRESUMO
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.
Assuntos
Blefaroplastia/história , Cirurgia Plástica/história , História do Século XX , Humanos , OntárioRESUMO
Breast cancer affects many women, but with advances in detection and treatment, survival rates have increased. Thus, it is important to understand that there are many reconstructive options available to help ease the psychological burden of mastectomy. Reconstructive options include tissue expander/implants, biologics, and several autologous tissue options, including pedicled latissimus and TRAM flaps, free TRAM flaps, and perforator flaps. We present a discussion of reconstructive techniques, the risks and benefits of each, and individual patient considerations that will help physicians to guide treatment options.
Assuntos
Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia Segmentar , Implantes de Mama , Feminino , Humanos , Mamoplastia/tendências , Obesidade/complicações , Radioterapia Adjuvante/efeitos adversos , Fumar/efeitos adversos , Retalhos Cirúrgicos , Fatores de TempoRESUMO
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.