Radiation exposure in pediatric videourodynamics: An evaluation of safety in comparison to voiding cystourethrogram.

Introduction: Children with spina bifida (SB) undergo a videourodynamic study (VUDS) or urodynamic study and voiding cystourethrogram (VCUG). A standardized protocol for imaging during a pediatric VUDS has not been established. Our aim is to quantify radiation exposure and establish a baseline for children with spina bifida (SB) undergoing VUDS in current practice at our institution.

Disruption of DNA methylation-mediated cranial neural crest proliferation and differentiation causes orofacial clefts in mice.

Orofacial clefts of the lip and palate are widely recognized to result from complex gene-environment interactions, but inadequate understanding of environmental risk factors has stymied development of prevention strategies. We interrogated the role of DNA methylation, an environmentally malleable epigenetic mechanism, in orofacial development. Expression of the key DNA methyltransferase enzyme DNMT1 was detected throughout palate morphogenesis in the epithelium and underlying cranial neural crest cell (cNCC) mesenchyme, a highly proliferative multipotent stem cell population that forms orofacial connective tissue.

FDA approval summary for lonafarnib (Zokinvy) for the treatment of Hutchinson-Gilford progeria syndrome and processing-deficient progeroid laminopathies.

The U.S. Food and Drug Administration recently approved lonafarnib as the first treatment for Hutchinson-Gilford progeria syndrome (HGPS) and processing-deficient progeroid laminopathies.

Urodynamic utilization in the adult spina bifida patient: An institutional review.

Purpose: To characterize common clinical indications for urodynamic, a bladder function test, in adults with spina bifida.

Methods: A retrospective chart review was performed for 215 patients seen in an adult multidisciplinary spina bifida clinic who were registered with the National Spina Bifida Patient Registry from October 2011 to October 2018. Descriptive statistics were used for statistical comparisons.

Translating pediatric urodynamics from clinic into collaborative research: Lessons and recommendations from the UMPIRE study group.

Pediatric patients present unique challenges in the performance and interpretation of urodynamic studies. Interpretation of urodynamics to guide clinical management at an institutional level is accepted as reliable. Challenges arise however when multi-site collaborations incorporate urodynamics into study design to determine primary or secondary outcomes or to direct decision-making.

A mechanism linking perinatal 2,3,7,8 tetrachlorodibenzo-p-dioxin exposure to lower urinary tract dysfunction in adulthood.

Benign prostatic hyperplasia/lower urinary tract dysfunction (LUTD) affects nearly all men. Symptoms typically present in the fifth or sixth decade and progressively worsen over the remainder of life. Here, we identify a surprising origin of this disease that traces back to the intrauterine environment of the developing male, challenging paradigms about when this disease process begins.

Single-cell analysis of mouse and human prostate reveals novel fibroblasts with specialized distribution and microenvironment interactions.

Stromal-epithelial interactions are critical to the morphogenesis, differentiation, and homeostasis of the prostate, but the molecular identity and anatomy of discrete stromal cell types is poorly understood. Using single-cell RNA sequencing, we identified and validated the in situ localization of three smooth muscle subtypes (prostate smooth muscle, pericytes, and vascular smooth muscle) and two novel fibroblast subtypes in human prostate. Peri-epithelial fibroblasts (APOD+) wrap around epithelial structures, whereas interstitial fibroblasts (C7+) are interspersed in extracellular matrix.

Urodynamic characteristics of neurogenic bladder in newborns with myelomeningocele and refinement of the definition of bladder hostility: Findings from the UMPIRE multi-center study.

Introduction: Infants with myelomeningocele are at risk for chronic kidney disease caused by neurogenic bladder dysfunction. Urodynamic evaluation plays a key role to risk stratify individuals for renal deterioration.

Objective: To present baseline urodynamic findings from the Urologic Management to Preserve Initial Renal function for young children with spina bifida (UMPIRE) protocol, to present the process that showed inadequacies of our original classification scheme, and to propose a refined definition of bladder hostility and categorization.

Incidence of Urinary Tract Infections in Newborns with Spina Bifida-Is Antibiotic Prophylaxis Necessary?

Purpose: Urinary tract infections commonly occur in patients with spina bifida and pose a risk of renal scarring. Routine antibiotic prophylaxis has been utilized in newborns with spina bifida to prevent urinary tract infections. We hypothesized that prophylaxis can safely be withheld in newborns with spina bifida until clinical assessment allows for risk stratification.

Progenitors in prostate development and disease.

The prostate develops by epithelial budding and branching processes that occur during fetal and postnatal stages. The adult prostate demonstrates remarkable regenerative capacity, with the ability to regrow to its original size over multiple cycles of castration and androgen administration. This capacity for controlled regeneration prompted the search for an androgen-independent epithelial progenitor in benign prostatic hyperplasia (BPH) and prostate cancer (PCa).

Urologic guidelines for the care and management of people with spina bifida.

Purpose: The life expectancy for people with spina bifida has increased, thus resulting in greater need for guidelines in urologic care in order to protect normal renal function, to develop strategies for urinary continence, and to advance independence through adult years.

Methods: The English literature was assessed from 2002-2015; greater than 300 publications identified. Case reports and opinion pieces were eliminated leaving 100 for in depth review.

The Roles of ZnT1 and ZnT4 in Glucose-Stimulated Zinc Secretion in Prostate Epithelial Cells.

Purpose: We have previously demonstrated by MRI that high glucose stimulates efflux of zinc ions from the prostate. To our knowledge, this phenomena had not been reported previously and the mechanism remains unknown. Here, we report some initial observations that provide new insights into zinc processing during glucose-stimulated zinc secretion (GSZS) in the immortalized human prostate epithelial cell line, PNT1A.

Urethral luminal epithelia are castration-insensitive cells of the proximal prostate.

Background: Castration-insensitive epithelial progenitors capable of regenerating the prostate have been proposed to be concentrated in the proximal region based on facultative assays. Functional characterization of prostate epithelial populations isolated with individual cell surface markers has failed to provide a consensus on the anatomical and transcriptional identity of proximal prostate progenitors.

Methods: Here, we use single-cell RNA sequencing to obtain a complete transcriptomic profile of all epithelial cells in the mouse prostate and urethra to objectively identify cellular subtypes.

Baseline Urinary Tract Imaging in Infants Enrolled in the UMPIRE Protocol for Children with Spina Bifida.

Purpose: The lifetime risk of renal damage in children with spina bifida is high but only limited baseline imaging data are available for this population. We evaluated a large prospective cohort of infants with spina bifida to define their baseline imaging characteristics.

Materials And Methods: The UMPIRE Protocol for Young Children with Spina Bifida is an iterative quality improvement protocol that follows a cohort of newborns at 9 United States centers.

DNA methylation in development and disease: an overview for prostate researchers.

Epigenetic mechanisms including DNA methylation are critical regulators of organismal development and tissue homeostasis. DNA methylation is the transfer of methyl groups to cytosines, which adds an additional layer of complexity to the genome. DNA methylation marks are recognized by the cellular machinery to regulate transcription.

Epithelial DNA methyltransferase-1 regulates cell survival, growth and maturation in developing prostatic buds.

DNA methyltransferase 1 (DNMT1) is required for embryogenesis but roles in late forming organ systems including the prostate, which emerges from the urethral epithelium, have not been fully examined. We used a targeted genetic approach involving a Shhcre recombinase to demonstrate requirement of epithelial DNA methyltransferase-1 (Dnmt1) in mouse prostate morphogenesis. Dnmt1 mutant urethral cells exhibit DNA hypomethylation, DNA damage, p53 accumulation and undergo cell cycle arrest and apoptosis.

A Cellular Anatomy of the Normal Adult Human Prostate and Prostatic Urethra.

A comprehensive cellular anatomy of normal human prostate is essential for solving the cellular origins of benign prostatic hyperplasia and prostate cancer. The tools used to analyze the contribution of individual cell types are not robust. We provide a cellular atlas of the young adult human prostate and prostatic urethra using an iterative process of single-cell RNA sequencing (scRNA-seq) and flow cytometry on ∼98,000 cells taken from different anatomical regions.

The development of a lifetime care model in comprehensive spina bifida care.

Purpose: To describe the development and implementation of the Children's of Alabama (COA) Spina Bifida (SB) Lifetime-Care-Model, including standardized care protocols and transition plan.

Methods: In 2010, members of the pediatric team at COA began to evaluate limitations in access to care for patients with SB at various stages of life. Through clinic surveys, observations, and caregiver report, a Lifetime-Care-Model was developed and implemented.

Age and factors associated with self-clean intermittent catheterization in patients with spina bifida.

Purpose: The purpose of this study is twofold: 1) to determine the age when a child with spina bifida (SB) will most likely transition from caregiver clean intermittent catheterization (CIC) to self-CIC, and 2) to identify factors associated with self-CIC in children older than that age.

Methods: This is a retrospective, single-institution cohort study of individuals with SB. Data were collected prospectively as part of the National Spina Bifida Patient Registry.

A folic acid-enriched diet attenuates prostate involution in response to androgen deprivation.

Background: Serum folate concentrations in the United States have risen since dietary folic acid fortification was first mandated in 1998. Although maternal folic acid offers protection against neural tube defects in conceptuses, its impact on other organ systems and life stages have not been fully examined. Here, we used a mouse model to investigate the impact of a Folic acid (FA) enriched diet on prostate homeostasis and response to androgen deprivation.

In vivo replacement of damaged bladder urothelium by Wolffian duct epithelial cells.

The bladder's remarkable regenerative capacity had been thought to derive exclusively from its own progenitors. While examining consequences of DNA methyltransferase 1 () inactivation in mouse embryonic bladder epithelium, we made the surprising discovery that Wolffian duct epithelial cells can support bladder regeneration. Conditional inactivation in mouse urethral and bladder epithelium triggers widespread apoptosis, depletes basal and intermediate bladder cells, and disrupts uroplakin protein expression.

Bladder Management and Continence Outcomes in Adults with Spina Bifida: Results from the National Spina Bifida Patient Registry, 2009 to 2015.

Purpose: Most children with spina bifida now survive into adulthood, although most have neuropathic bladder with potential complications of incontinence, infection, renal damage and diminished quality of life. In this study we sought to 1) describe contemporary bladder management and continence outcomes of adults with spina bifida, 2) describe differences from younger individuals and 3) assess for association with socioeconomic factors.

Materials And Methods: We analyzed data on bladder management and outcomes in adults with spina bifida from the National Spina Bifida Patient Registry.