To investigate the video-urodynamic and pelvic floor electrophysiological characteristics in patients with traumatic spinal cord injury (SCI).This retrospective reviewed the clinical records, urodynamic and pelvic floor electrophysiological data of 647 patients with traumatic SCI and out of spinal shock. Patients were classified based on American Spinal Injury Association (ASIA) Impairment Scale and urodynamic findings.Of the 647 patients, detrusor overactivity (DO) with or without detrusor sphincter dyssynergia (DSD) was found in 79.5%, 61%, 35.2%, 35%, and 19.2% of patients with cervical, thoracic (T1-9), thoracic (T10-12), lumbar, and conical cauda injury, respectively. Other patients manifested detrusor areflexia (DA). Patients with DO and/or DSD had a longer duration of SCI at each injury level than patients with DA. In suprasacral injury patients with DA, 63.0% (58 of 92) had a normal bulbocavernosus reflex (BCR) response. Compared with patients without bladder sensation (BS), bladder capacity during urine leakage was far higher in those with BS. The manifestation of BCR and somatosensory-evoked potential (SEP) was associated with the level of injury.This study showed a significant correlation between the level of SCI and video-urodynamic findings, but clinical examination cannot by predict bladder function; urodynamic testing is also necessary. In addition, the role of BCR and SEP for guiding bladder management is limited. Moreover, BS is important for urinary control in patients with traumatic SCI.
Background: Intradetrusor injection of botulinum toxin A (BTX-A) is an effective treatment for overactive bladder (OAB). However, the occurrence of adverse events associated with BTX-A injection therapy hinders its acceptance among patients and its clinical promotion. Intravesical instillation of BTX-A offers a promising alternative to injection therapy for treating OAB. Nevertheless, due to the presence of the bladder permeability barrier (BPB) and the high molecular weight of BTX-A, direct instillation is unable to penetrate the bladder urothelium. Purpose: This study aims to investigate the safety and feasibility of ultrasound-assisted intravesical delivery of BTX-A and its potential benefits in a rat model of bladder hyperactivity induced by acetic acid instillation. Methods: Hengli BTX-A and microbubbles (MB) were mixed and prepared as a novel complex. The size distribution and zeta potentials of the complex were measured. On day 1, rats' bladders were instilled with 1 mL of saline, BTX-A (20 U in 1 mL), MB, or MB-BTX-A (20 U in 1 mL) complex with or without ultrasound (US) exposure (1 MHz, 1.5 W/cm2, 50% duty cycle, sonication for 10 s with a 10-s pause for a total of 10 min). The instillations were maintained for 30 min. After 7 days, cystometry was performed by filling the bladder with saline and 0.3% acetic acid (AA). Bladders were collected, weighed, and processed for immunoblotting, enzyme-linked immunosorbent assay (ELISA), histologic, and immunofluorescence analyses. Expression and distribution of SNAP-25 and SNAP-23 were assessed using Western blot and immunofluorescence. Calcitonin gene-related peptide (CGRP) in the bladder was detected using ELISA. Results: Intercontraction intervals (ICI) decreased by 72.99%, 76.16%, and 73.96% in rats pretreated with saline, BTX-A, and US + MB, respectively. However, rats treated with US + MB + BTX-A showed a significantly reduced response to AA instillation (57.31% decrease in ICI) without affecting amplitude, baseline pressure, or threshold pressure. Rats treated with US + MB + BTX-A exhibited increased cleavage of SNAP-25 and CGRP expression compared to the control group. Conclusion: Ultrasound-assisted intravesical delivery of BTX-A, with the assistance of MB cavitation, led to cleavage of SNAP-25, inhibition of calcitonin gene-related peptide release from afferent nerve terminals, and amelioration of acetic acid-induced bladder hyperactivity. These results support ultrasound-assisted intravesical delivery as an efficient non-injection method for administering BTX-A.
Objectives: To verify the safety and effectiveness of a novel micro-implantable wireless nerve stimulation device in healthy adult beagles and evaluate the feasibility of using the device in clinical practice. Methods: The stimulator was experimentally implanted into the quadriceps femoris of three adult beagles. The animals were subjected to training on daily basis for 14 days, and the threshold test was administered once a week. At the end, we analyzed the images of light microscopy and electron microscopy. Results: The implantation was easy to perform and the whole stimulation system worked stably and reliably. The stim-ulation threshold was stable. During the process, the stimulator did not move or cause damage to adjacent tissues. The whole system showed a good biocompatibility with recipient animals. The stimulator could induce muscular contraction and enhance the motor function of muscles. Conclusions: The preliminary results showed that the stimulator could be safely implanted into animal body, with good tissue compatibility, stability and reliability. In addition, it also worked well in eliciting muscle contraction. It promises to be used for the treatment of stress urinary incontinence in future.
In the past, many experimental or clinical studies were carried out to develop promising therapies for neurogenic lower urinary tract dysfunction (LUTD). Although still a long way from clinical application, many approaches seem promising and may bring a clinical revolution for treatment of neurogenic LUTD. In this chapter, we will discuss research progress, emerging concepts, and potential procedures, and explore new directions in the field of neurogenic LUTD, including intravesical delivery of Botulinum toxin A, tissue-engineered bladder, bioprinting technology, closed-loop neuromodulation, optogenetic neuromodulation, gene therapy, mechanisms of neuromodulation, and biological therapeutics for urinary tract infections (UTIs).
Abstract Purpose To investigate the abnormalities of functional connectivity (FC) within the prefrontal cortex (PFC) of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) based on resting state functional near‐infrared spectroscopy (rs‐fNIRS) data using FC matrix analysis. Materials and Methods Ten patients with IC/BPS (females, 9; mean age, 56.9 ± 12.432 years) and 15 age‐ and gender‐matched healthy controls (HC) (females, 12; mean age, 55.067 ± 7.46 years) participated in this rs‐fNIRS study. Two rs‐fNIRS scans were performed (when the bladder was empty and when the desire to void was strong). The Pearson's correlation coefficient between the time series of the 22 channels was calculated to obtain a 22 × 22 FC matrix for each subject. A two‐sample t ‐test ( p < .05) was performed to compare group differences in the FC matrix between patients with IC/BPS and HC. Results FC was significantly decreased within the PFC in the IC/BPS group based on a two‐sample t ‐test ( p < .05) compared with HC. FC decreased in a wider range of brain regions during the strong desire to void state (4 brain regions and 28 edges) when compared with the empty bladder state (3 brain regions and 18 edges). Conclusion FC abnormalities in IC/BPS patients may lead to frontal lobe disorders involved in processing sensory integration, motivation drive, emotional control, and decision‐making whether to urinate, leading to urinary control dysfunction manifested as typical clinical IC/BPS symptoms. Our results may provide new insight into the pathogenesis of IC/BPS and new brain biomarkers for diagnosis.
Protein libraries are essential to the field of protein engineering. Increasingly, probabilistic protein design is being used to synthesize combinatorial protein libraries, which allow the protein engineer to explore a vast space of amino acid sequences, while at the same time placing restrictions on the amino acid distributions. To this end, if site-specific amino acid probabilities are input as the target, then the codon nucleotide distributions that match this target distribution can be used to generate a partially randomized gene library. However, it turns out to be a highly nontrivial computational task to find the codon nucleotide distributions that exactly matches a given target distribution of amino acids. We first showed that for any given target distribution an exact solution may not exist at all. Formulated as a constrained optimization problem, we then developed a genetic algorithm-based approach to find codon nucleotide distributions that match as closely as possible to the target amino acid distribution. As compared with the previous gradient descent method on various objective functions, the new method consistently gave more optimized distributions as measured by the relative entropy between the calculated and the target distributions. To simulate the actual lab solutions, new objective functions were designed to allow for two separate sets of codons in seeking a better match to the target amino acid distribution.
A molecular electronegativity-distance vector(MEDV),which has been developed according to classification of the types of non-hydrogen atoms,is used to describe the chemical structure of a series of fluorinated phenolic compounds.The MEDV descriptors are calculated through a relative electronegativity and a relative distance of the fluorinated phenolic compounds atoms.The QSAR model of 5 varieables of the fluorinated phenolic compounds is built up by multiple linear regression(MLR) and the correlation coefficients(R) of molecular modeling is 0.914.The predicted and observed toxicities of studied compounds have been proved to be in accord.Cross-validation of the models,which contain selected vectors,are performed by leave-one-out procedure(LOO) and the satisfied results with correlation coefficients(RCV) of 0.856;The results show that the models constructed can provide estimation stability and favorable predictive ability.
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