Endothelial Cell Capture of Heparin-Binding Growth Factors under Flow

Circulation is an important delivery method for both natural and synthetic molecules, but microenvironment interactions, regulated by endothelial cells and critical to the molecule's fate, are difficult to interpret using traditional approaches. In this work, we analyzed and predicted growth factor capture under flow using computer modeling and a three-dimensional experimental approach that includes pertinent circulation characteristics such as pulsatile flow, competing binding interactions, and limited bioavailability. An understanding of the controlling features of this process was desired. The experimental module consisted of a bioreactor with synthetic endothelial-lined hollow fibers under flow. The physical design of the system was incorporated into the model parameters. The heparin-binding growth factor fibroblast growth factor-2 (FGF-2) was used for both the experiments and simulations. Our computational model was composed of three parts: (1) media flow equations, (2) mass transport equations and (3) cell surface reaction equations. The model is based on the flow and reactions within a single hollow fiber and was scaled linearly by the total number of fibers for comparison with experimental results. Our model predicted, and experiments confirmed, that removal of heparan sulfate (HS) from the system would result in a dramatic loss of binding by heparin-binding proteins, but not by proteins that do not bind heparin. The model further predicted a significant loss of bound protein at flow rates only slightly higher than average capillary flow rates, corroborated experimentally, suggesting that the probability of capture in a single pass at high flow rates is extremely low. Several other key parameters were investigated with the coupling between receptors and proteoglycans shown to have a critical impact on successful capture. The combined system offers opportunities to examine circulation capture in a straightforward quantitative manner that should prove advantageous for biologicals or drug delivery investigations

The Ups and Downs of Mutation Frequencies during Aging Can Account for the Apert Syndrome Paternal Age Effect

Apert syndrome is almost always caused by a spontaneous mutation of paternal origin in one of two nucleotides in the fibroblast growth factor receptor 2 gene (FGFR2). The incidence of this disease increases with the age of the father (paternal age effect), and this increase is greater than what would be expected based on the greater number of germ-line divisions in older men. We use a highly sensitive PCR assay to measure the frequencies of the two causal mutations in the sperm of over 300 normal donors with a wide range of ages. The mutation frequencies increase with the age of the sperm donors, and this increase is consistent with the increase in the incidence rate. In both the sperm data and the birth data, the increase is non-monotonic. Further, after normalizing for age, the two Apert syndrome mutation frequencies are correlated within individual sperm donors. We consider a mathematical model for germ-line mutation which reproduces many of the attributes of the data. This model, with other evidence, suggests that part of the increase in both the sperm data and the birth data is due to selection for mutated premeiotic cells. It is likely that a number of other genetic diseases have similar features

Radiographic Evaluation of Intussusception: Utility of Left-Side-Down Decubitus View

Purpose: To assess the incremental value of the left-side-down decubitus view in radiographic evaluation of ileocolic intussusception

Percutaneous ultrasound-guided ganglion fenestration in children: initial results

To evaluate our pediatric experience with percutaneous ultrasound-guided fenestration of ganglia (PUGG). Retrospective study of pediatric patients who underwent PUGG from June 2016 to October 2018 at a free-standing tertiary referral academic children's hospital with a minimum of 6 months follow-up. Electronic medical records, picture archiving system, and post-procedural calls were utilized for patient demographics, lesion characteristics, procedure details, and recurrence. The procedure itself consisted of assessment by Child Life, application of topical anesthetic cream, sterile preparation and draping, and intra-procedural ultrasound guidance for local anesthetic instillation, ganglion aspiration, fenestration, and intra-remnant steroid instillation. Post-procedure care included an ice pack, compression dressing for 48 h, and 4 weeks of brace wear and activity restriction. Forty-five patients met the inclusion criteria, ages 3-18 years, mean 13.5 years, and female to male ratio of 2:1. Ganglion locations consisted of 80% (36/45) in the wrist and 20% (9/45) in other locations (elbow, ankle, and foot). Ninety-eight percent (44/45) of procedures were performed non-sedated, including 20% (9/44) between ages 7 and 11 years. 28.9% (13/45) of ganglia recurred, the earliest at 3 weeks, the latest at 10 months, and an average of 3 months' time. No complication occurred and no patients required post-procedural narcotics or Emergency Department visitation for pain control. Percutaneous ultrasound-guided fenestration of ganglia (PUGG) is a safe, minimally invasive alternative to surgical excision in the pediatric population, which can be performed without sedation and does not leave a scar

Hamate-pisiform coalition complicated by fracture in a pediatric patient

Coalition of the carpal bones is a relatively uncommon anatomic anomaly. The majority of carpal coalitions occur between the lunate and triquetrum. There are rare reports of coalition involving the hamate and pisiform. We report a case of a previously asymptomatic male who sustained minor trauma and was found to have hamate-pisiform coalition complicated by a minimally displaced pisiform fracture. Keywords: Pediatric carpal coalition, Hamate-pisiform, Pisiform-hamat