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Since 2011 we have been following prospectively myelomeningocele patients treated in utero with particular interest to patients with sphincter weakness/deficiency. We investigated the changes of bladder pattern and upper urinary tract with time in children who underwent in utero repair and had low-pressure incontinence based on urodynamic evaluation (UE).

From the 120 patients in our database, 117 had at least one UE. Of these, 30 were classified as incontinent when leaking at low pressure (<40 cmH20). We reviewed clinical evaluation, urinary tract ultrasound, voiding cystourethrography (VCUG), and other UE parameters at first and last evaluation.

We found 30 cases (25.64%). Mean age at initial evaluation was 4.97 months followed by UE done initially at mean age of 5.73 months. Follow-up was 28.4 months. Febrile urinary tract infection has been found in four patients (13.3%), hydronephrosis in four patients, and bladder neck thickening in three (10%). The VCUG showed vesicoureteral reflux in three cases (3/27, 11.1%). A total of 90% of patients had detrusor overactivity with mean maximum detrusor pressure (33.37 cmH20). Only 16.67% of patients showed normal bladder capacity. From the 30 patients, 23 had at least two UE. We noticed a change of bladder pattern as follows six patients became of high-risk pattern, five normal, and two with underactive bladder pattern. The average interval between the first and last UE was 25.5 months (median 15 months).

We concluded that 43.47% of patients with low DLPP have kept the incontinent pattern. Anacetrapib solubility dmso If the initial LPP was below 30 cmH20, 70% remained with the incontinet pattern.

We concluded that 43.47% of patients with low DLPP have kept the incontinent pattern. If the initial LPP was below 30 cmH20, 70% remained with the incontinet pattern.Reconstituted model membrane systems are powerful platforms to tackle interesting problems existing in membrane biology. One of the barriers to efficient drug delivery, as therapeutics to disease, is the physical membrane barrier of the cell. Small molecule can typically diffuse through the membrane; however, biomolecules such as proteins or nucleic acids cannot passively diffuse the bilayer and thus much research has been geared to engineering protein and/or nucleic acids delivery methods. One delivery method uses cell penetrating peptides (CPPs). In this chapter, we introduce the model "membrane army" arranged in dimple chip to study the delivery of β-galactosidase by a CPP known as Pep-1. This method uses droplet interface bilayer technology (DIB). It accelerates the speed to screen through the working conditions in CPP-assisted protein translocations because each chip provides dimples that can accommodate 36 pairs of droplets or 18 model bilayers. We will use one of the successful translocation conditions of β-galactosidase delivery as the example to illustrate how the model "membrane army" is built and utilized.Because of the high sensitivity of lipid bilayers to external pressure fluctuations, a major challenge in functional studies of biological pores or ion channels is the difficulty in exchanging solutions rapidly while maintaining the stability of the lipid bilayer in a model membrane. Here we describe a droplet-interface bilayer-based perfusion system that has been routinely used in our research and is currently the most robust and stable perfusion system that provides prompt solution exchange surrounding a lipid bilayer. In this model membrane system, solutions can be completely exchanged within 1-2 s to obtain prompt responses of a lipid bilayer or membrane pores to the membrane environments. Also, our system is stable enough to sustain continuous perfusions up to at least dozens of minutes. To demonstrate, we show that acidification-induced protein channel insertion, substrate binding to protein channels, and pH gradient-driven protein translocation of anthrax toxin can be sequentially initiated by continuous perfusions in our system. Moreover, by rapidly switching the solutions, the protein translocation based on ratchet mechanisms can be paused and reinitiated iteratively in our system. Overall, this perfusion system provides a controllable and reliable solution exchange platform for investigations of pores and translocations on lipid bilayers.Droplet interface bilayer (DIB) is a method of fabricating lipid bilayer membrane by contacting two aqueous droplets coated with a monolayer of lipid molecules in oil media. Lipids coat the droplet surface either by vesicles fusing to the water-oil interface from the droplet side or diffusing toward the interface from the oil side, thereby forming a lipid monolayer. With the DIB technique, nanoliter amounts of aqueous solution is needed and one may obtain two different compositions of monolayers to form asymmetric bilayer which is difficult to replicate by other in vitro lipid membrane methods. Here, a DIB-based protocol is reported to fabricate a stable lipid bilayer membrane to perform single-channel electrophysiology on a pore-forming toxin.This chapter presents a mathematical formulation for the translocation process of a vesicle through a narrow pore. The effect of the deformation of the vesicle while passing through the pore causes a penalty in the free energy, while the existence of an external driving force assists. We formulate the free energy landscape of the vesicle in terms of bending and stretching energy and use Fokker-Plank formalism to calculate the first-passage translocation time. We also address various modifications that can be done to this approach to make it work for different systems.Bacterial porins often exhibit ion conductance and gating behavior which can be modulated by pH. However, the underlying control mechanism of gating is often complex, and direct inspection of the protein structure is generally insufficient for full mechanistic understanding. Here we describe Pretzel, a computational framework that can effectively model loop-based gating events in membrane proteins. Our method combines Monte Carlo conformational sampling, structure clustering, ensemble energy evaluation, and a topological gating criterion to model the equilibrium gating state under the pH environment of interest. We discuss details of applying Pretzel to the porin outer membrane protein G (OmpG).