Does Treatment With OnabotulinumtoxinA Improve the Quality of Life in Patients With Urinary Incontinence Not Adequately Controlled With Anticholinergics?

OBJECTIVE: The objective of this selective EBM review is to determine whether or not treatment with onabotulinumtoxinA improves the quality of life in patients with urinary incontinence not adequately controlled with anticholinergics. STUDY DESIGN: Review of three English language, randomized controlled trials published in 2013. DATA SOURCES: Randomized, double-blind, controlled clinical trials comparing onabotulinumtoxinA intradetrusor injections with saline placebo. All articles were found using PubMed. OUTCOMES MEASURED: Each of the three trials assessed the patient’s quality of life after treatment with onabotulinumtoxinA using the following assessment tools: Incontinence Quality of Life Questionnaire (I-QOL), Modified Overactive Bladder Patient Satisfaction with Treatment Questionnaire (OAB-PSTQ), King’s Health Questionnaire (KHQ), Patient Global Assessment (PGA), and Treatment Benefit Scale. RESULTS: Both the Chancellor et al. and the Sussman et al. studies found a statistically significant improvement in the change from baseline in the I-QOL and OAB-PSTQ for the patients who received onabotulinumtoxinA compared to placebo (p value \u3c 0.001). Nitti et al. demonstrated an improvement range of 19.6 to 23.9 ± SD change from baseline in the I-QOL score for the onabotulinumtoxinA treatment group. 60.8% of the experimental group in Nitti et al. reported a positive treatment response after onabotulinumtoxinA while only 29.2% of placebo patients reported this response (p value \u3c 0.001). Sussman et al established an inverse correlation between I-QOL total scores and UI frequency with a Pearson’s correlation coefficient of -0.508 at week 12 establishing that decreased frequency in urinary incontinence events are associated with improved quality of life. CONCLUSIONS: Based on the three trials, onabotulinumtoxinA does improve quality of life in patients with urinary incontinence not adequately controlled with anticholinergics by improving patient satisfaction with treatment, urinary incontinence symptoms, and healthcare related quality of life

Experimental stand for investigation of induction hardening of steel elements

The experimental stand for investigation of induction surface hardening of gear wheels was described in the paper. In order to control parameters of the process a specialized equipment for identification of all important process parameters including registration of temperature changes in time and measurements of current intensity was installed. Exemplary results are presented. It is planned that the stand will be used as a demonstrator for a presentation of advantages of modern induction hardening technologies

Assessing Human Error Against a Benchmark of Perfection

An increasing number of domains are providing us with detailed trace data on human decisions in settings where we can evaluate the quality of these decisions via an algorithm. Motivated by this development, an emerging line of work has begun to consider whether we can characterize and predict the kinds of decisions where people are likely to make errors. To investigate what a general framework for human error prediction might look like, we focus on a model system with a rich history in the behavioral sciences: the decisions made by chess players as they select moves in a game. We carry out our analysis at a large scale, employing datasets with several million recorded games, and using chess tablebases to acquire a form of ground truth for a subset of chess positions that have been completely solved by computers but remain challenging even for the best players in the world. We organize our analysis around three categories of features that we argue are present in most settings where the analysis of human error is applicable: the skill of the decision-maker, the time available to make the decision, and the inherent difficulty of the decision. We identify rich structure in all three of these categories of features, and find strong evidence that in our domain, features describing the inherent difficulty of an instance are significantly more powerful than features based on skill or time.Comment: KDD 2016; 10 page

Improving In Vivo Brain Delivery of Monoclonal Antibody Using Novel Cyclic Peptides

This work is licensed under a Creative Commons Attribution 4.0 International License.Many proteins can be used to treat brain diseases; however, the presence of the blood–brain barrier (BBB) creates an obstacle to delivering them into the brain. Previously, various molecules were delivered through the paracellular pathway of the BBB via its modulation, using ADTC5 and HAV6 peptides. This study goal was to design new cyclic peptides with N-to-C terminal cyclization for better plasma stability and modulation of the BBB. Cyclic HAVN1 and HAVN2 peptides were derived from a linear HAV6 peptide. Linear and N-to-C terminal cyclic ADTHAV peptides were designed by combining the sequences of ADTC5 and HAV6. These novel cyclic peptides were used to deliver an IRdye800CW-labeled IgG monoclonal antibody into the brain. Cyclic HAVN1 and HAVN2 peptides deliver IgG into the brain, while the parent linear HAV6 peptide does not. Cyclic and linear ADTHAV and ADTC5 peptides enhanced brain delivery of IgG mAb, in which cyclic ADTHAV peptide was better than linear ADTHAV (p = 0.07). Cyclic ADTHAV and ADTC5 influenced the distribution of IgG mAb in other organs while HAV6, HAVN1 and HAVN2 did not. In summary, the novel cyclic peptides are generally better BBB modulators than their linear counterparts for delivering IgG mAb into the brain

Glutamate receptor exocytosis and spine enlargement during chemically induced long-term potentiation

The changes in synaptic morphology and receptor content that underlie neural plasticity are poorly understood. Here, we use a pH-sensitive green fluorescent protein to tag recombinant glutamate receptors and monitor their dynamics onto dendritic spine surfaces. We show that chemically induced long-term potentiation (chemLTP) drives robust exocytosis of AMPA receptors. In contrast, the same stimulus produces a small reduction of NMDA receptors from the spine surface. chemLTP produces similar modification of small and large spines. Interestingly, during chemLTP induction, spines increase in volume before accumulation of AMPA receptors on their surface, indicating that distinct mechanisms underlie changes in morphology and receptor content

The Effect of Walking an Unfamiliar Versus Companion Dog on Mood, Exercise Enjoyment, and Heart Rate: A Pilot Field Study

Topics in Exercise Science and Kinesiology Volume 2: Issue 1, Article 3, 2021. Background: Walking unfamiliar dogs, such as therapy dogs, has been shown to improve physiological exercise responses and exercise adherence, but whether walking a companion dog results in superior benefits is currently unknown. The purpose of the current pilot field study was to elucidate preliminary evidence of how walking an unfamiliar or companion dog influences mood, exercise enjoyment, and heart rate during a 1.5-mile walk. Methods: Participants (n=8) walked 1.5-miles at their own pace with an unfamiliar or companion dog while mood, exercise enjoyment, and heart rate were measured. Point of application #1: Walking an unfamiliar dog resulted in improved pre- to post- exercise mood changes compared to walking their own companion dog. Point of application #2: Enjoyment of exercise was higher while walking the unfamiliar dog compared to the companion dog. Point of application #3: Mean exercise heart rate was significantly higher while walking the unfamiliar versus companion dog although time to completion of the 1.5-miles was unaffected

Noninvasive Brain Delivery and Efficacy of BDNF to Stimulate Neuroregeneration and Suppression of Disease Relapse in EAE Mice

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © 2019 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.molpharmaceut.9b00644.The number of FDA-approved protein drugs (biologics), such as antibodies, antibody–drug conjugates, hormones, and enzymes, continues to grow at a rapid rate; most of these drugs are used to treat diseases of the peripheral body. Unfortunately, most of these biologics cannot be used to treat brain diseases such as Alzheimer’s disease (AD), multiple sclerosis (MS), and brain tumors in a noninvasive manner due to their inability to permeate the blood–brain barrier (BBB). Therefore, there is a need to develop an effective method to deliver protein drugs into the brain. Here, we report a proof of concept to deliver a recombinant brain-derived neurotrophic factor (BDNF) to the brains of healthy and experimental autoimmune encephalomyelitis (EAE) mice via intravenous (iv) injections by co-administering BDNF with a BBB modulator (BBBM) peptide ADTC5. Western blot evaluations indicated that ADTC5 enhanced the brain delivery of BDNF in healthy SJL/elite mice compared to BDNF alone and triggered the phosphorylation of TrkB receptors in the brain. The EAE mice treated with BDNF + ADTC5 suppressed EAE relapse compared to those treated with BDNF alone, ADTC5 alone, or vehicle. We further demonstrated that brain delivery of BDNF induced neuroregeneration via visible activation of oligodendrocytes, remyelination, and ARC and EGR1 mRNA transcript upregulation. In summary, we have demonstrated that ADTC5 peptide modulates the BBB to permit noninvasive delivery of BDNF to exert its neuroregeneration activity in the brains of EAE mice

The effects of Tween-80 on the integrity of solutions of capsaicin: useful information for performing tussigenic challenges

ABSTRACT: BACKGROUND: Because variable results of capsaicin challenges may be due to the incomplete solubility of capsaicin, we sought to determine if the use of Tween-80 in solutions of capsaicin improves actual concentrations of freshly prepared and stored solutions. METHODS: Capsaicin solutions ranging from 0.5-128 muM were mixed with and without Tween-80. Samples of various concentrations were then stored under 4 environmental conditions: 4 degrees C, protected from light; room temperature, protected from light; room temperature, exposed to light; -20 degrees C. All samples were analyzed initially, and at 2 and 4 months. RESULTS: While freshly prepared solutions with Tween-80 had consistently higher concentrations than those prepared without Tween-80 (83% vs. 69%), Tween-80 does not facilitate complete solubility. For solutions stored at 4 degrees C and protected from light, there was a significant decrease after 2 months in low concentration solutions of both the Tween-80 and non-Tween-80 solutions. Both Tween-80 and non-Tween-80 containing solutions significantly decreased in concentration after 2 months when stored at room temperature and protected from light, room temperature and exposed to light, and -20 degrees C. Concentrations of solutions made of 4 muM or higher are stable when stored at 4 degrees C and protected from light for 4 months. CONCLUSION: While the inherent difficulty of forcing capsaicin into solution cannot be eliminated, it can be improved with Tween-80. However, the addition of Tween-80 does not prevent the breakdown of stored capsaicin solutions. We recommend preparing and storing capsaicin solutions according to the methods and results of this study

First-order transitions and triple point on a random p-spin interaction model

The effects of competing quadrupolar- and spin-glass orderings are investigated on a spin-1 Ising model with infinite-range random $p$-spin interactions. The model is studied through the replica approach and a phase diagram is obtained in the limit $p\to\infty$. The phase diagram, obtained within replica-symmetry breaking, exhibits a very unusual feature in magnetic models: three first-order transition lines meeting at a commom triple point, where all phases of the model coexist.Comment: 9 pages, 2 ps figures include