Patient-Reported Side Effects of Intradetrusor Botulinum Toxin Type A for Idiopathic Overactive Bladder Syndrome

Objective: The aim of the study was a prospective assessment of patient-reported side effects in an open-label study after intradetrusor botulinum toxin injections for idiopathic overactive bladder (OAB). Patients and Methods: Botulinum toxin A injection was performed in 56 patients with idiopathic OAB. Patients were followed up for 6 months concerning side effects and patients' satisfaction. Results: Different types of side effects were assessed such as dry mouth (19.6%), arm weakness (8.9%), eyelid weakness (8.9%), leg weakness (7.1%), torso weakness (5.4%), impaired vision (5.4%) and dysphagia (5.4%). In all cases, symptoms were mild and transient. Urological complications such as gross hematuria (17.9%), acute urinary retention (8.9%) and acute urinary tract infection (7.1%) were noticed. In all cases, acute urinary retention was transient and treated with temporary intermittent self-catheterization. There was no statistically significant correlation between dosage and observed side effects. Patients' satisfaction rate was high (71.4%). Conclusion: Intradetrusor injection of botulinum toxin was associated with a high rate of neurourological side effects. In general, side effects were transient, mild and did not require special treatment. Copyright (C) 2010 S. Karger AG, Base

Epigenetic regulation of cyclooxygenase-2 by methylation of c8orf4 in pulmonary fibrosis

Fibroblasts derived from the lungs of patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) produce low levels of prostaglandin (PG) E(2), due to a limited capacity to up-regulate cyclooxygenase-2 (COX-2). This deficiency contributes functionally to the fibroproliferative state, however the mechanisms responsible are incompletely understood. In the present study, we examined whether the reduced level of COX-2 mRNA expression observed in fibrotic lung fibroblasts is regulated epigenetically. The DNA methylation inhibitor, 5-aza-2′-deoxycytidine (5AZA) restored COX-2 mRNA expression by fibrotic lung fibroblasts dose dependently. Functionally, this resulted in normalization of fibroblast phenotype in terms of PGE(2) production, collagen mRNA expression and sensitivity to apoptosis. COX-2 methylation assessed by bisulfite sequencing and methylation microarrays was not different in fibrotic fibroblasts compared with controls. However, further analysis of the methylation array data identified a transcriptional regulator, chromosome 8 open reading frame 4 (thyroid cancer protein 1, TC-1) (c8orf4), which is hypermethylated and down-regulated in fibrotic fibroblasts compared with controls. siRNA knockdown of c8orf4 in control fibroblasts down-regulated COX-2 and PGE(2) production generating a phenotype similar to that observed in fibrotic lung fibroblasts. Chromatin immunoprecipitation demonstrated that c8orf4 regulates COX-2 expression in lung fibroblasts through binding of the proximal promoter. We conclude that the decreased capacity of fibrotic lung fibroblasts to up-regulate COX-2 expression and COX-2-derived PGE(2) synthesis is due to an indirect epigenetic mechanism involving hypermethylation of the transcriptional regulator, c8orf4

Association Analysis of the Extended MHC Region in Celiac Disease Implicates Multiple Independent Susceptibility Loci

Celiac disease is a common autoimmune disease caused by sensitivity to the dietary protein gluten. Forty loci have been implicated in the disease. All disease loci have been characterized as low-penetrance, with the exception of the high-risk genotypes in the HLA-DQA1 and HLA-DQB1 genes, which are necessary but not sufficient to cause the disease. The very strong effects from the known HLA loci and the genetically complex nature of the major histocompatibility complex (MHC) have precluded a thorough investigation of the region. The purpose of this study was to test the hypothesis that additional celiac disease loci exist within the extended MHC (xMHC). A set of 1898 SNPs was analyzed for association across the 7.6 Mb xMHC region in 1668 confirmed celiac disease cases and 517 unaffected controls. Conditional recursive partitioning was used to create an informative indicator of the known HLA-DQA1 and HLA-DQB1 high-risk genotypes that was included in the association analysis to account for their effects. A linkage disequilibrium-based grouping procedure was utilized to estimate the number of independent celiac disease loci present in the xMHC after accounting for the known effects. There was significant statistical evidence for four new independent celiac disease loci within the classic MHC region. This study is the first comprehensive association analysis of the xMHC in celiac disease that specifically accounts for the known HLA disease genotypes and the genetic complexity of the region

Building block libraries and structural considerations in the self-assembly of polyoxometalate and polyoxothiometalate systems

Inorganic metal-oxide clusters form a class of compounds that are unique in their topological and electronic versatility and are becoming increasingly more important in a variety of applications. Namely, Polyoxometalates (POMs) have shown an unmatched range of physical properties and the ability to form structures that can bridge several length scales. The formation of these molecular clusters is often ambiguous and is governed by self-assembly processes that limit our ability to rationally design such molecules. However, recent years have shown that by considering new building block principles the design and discovery of novel complex clusters is aiding our understanding of this process. Now with current progress in thiometalate chemistry, specifically polyoxothiometalates (POTM), the field of inorganic molecular clusters has further diversified allowing for the targeted development of molecules with specific functionality. This chapter discusses the main differences between POM and POTM systems and how this affects synthetic methodologies and reactivities. We will illustrate how careful structural considerations can lead to the generation of novel building blocks and further deepen our understanding of complex systems

Generating SQL queries from visual specifications

Abstract: Structured Query Language (SQL) is the most widely used declarative language for accessing relational databases, and an essential topic in introductory database courses in higher learning institutions. Despite the intuitiveness of SQL, formulating and comprehending written queries can be confusing, especially for undergraduate students. One major reason for this is that the simple syntax of SQL is often misleading and hard to comprehend. A number of tools have been developed to aid the comprehension of queries and improve the mental models of students concerning the underlying logic of SQL. Some of these tools employed visualisation and animation in their approach to aid the comprehension of SQL. This paper presents an interactive comprehension aid based on visualisation, specifically designed to support the SQL SELECT statement, an area identified in the literature as problematic for students. The visualisation tool uses visual specifications depicting SQL operations to build queries. This is expected to reduce the cognitive load of a student who is learning SQL. We have shown with an online survey that adopting visual specifications in teaching systems assist students in attaining a richer learning experience in introductory database courses

Hospital-acquired Clostridium difficile-associated disease in the intensive care unit setting: epidemiology, clinical course and outcome

<p>Abstract</p> <p>Background</p> <p><it>Clostridium difficile</it>-associated disease (CDAD) is a serious nosocomial infection, however few studies have assessed CDAD outcome in the intensive care unit (ICU). We evaluated the epidemiology, clinical course and outcome of hospital-acquired CDAD in the critical care setting.</p> <p>Methods</p> <p>We performed a historical cohort study on 58 adults with a positive <it>C. difficile </it>cytotoxin assay result occurring in intensive care units.</p> <p>Results</p> <p>Sixty-two percent of patients had concurrent infections, 50% of which were bloodstream infections. The most frequently prescribed antimicrobials prior to CDAD were anti-anaerobic agents (60.3%). Septic shock occurred in 32.8% of CDAD patients. The in-hospital mortality was 27.6%. Univariate analysis revealed that SOFA score, at least one organ failure and age were predictors of mortality. Charlson score ≥3, gender, concurrent infection, and number of days with diarrhea before a positive <it>C. difficile </it>toxin assay were not significant predictors of mortality on univariate analysis. Independent predictors for death were SOFA score at infection onset (per 1-point increment, OR 1.40; CI95 1.13–1.75) and age (per 1-year increment, OR 1.10; CI95 1.02–1.19).</p> <p>Conclusion</p> <p>In ICU patients with CDAD, advanced age and increased severity of illness at the onset of infection, as measured by the SOFA score, are independent predictors of death.</p

Nuclear Magnetic Resonance Imaging with 90 nm Resolution

Magnetic resonance imaging, based on the manipulation and detection of nuclear spins, is a powerful imaging technique that typically operates on the scale of millimeters to microns. Using magnetic resonance force microscopy, we have demonstrated that magnetic resonance imaging of nuclear spins can be extended to a spatial resolution better than 100 nm. The two-dimensional imaging of 19F nuclei was done on a patterned CaF2 test object, and was enabled by a detection sensitivity of roughly 1200 nuclear spins. To achieve this sensitivity, we developed high-moment magnetic tips that produced field gradients up to 1.4x10^6 T/m, and implemented a measurement protocol based on force-gradient detection of naturally occurring spin fluctuations. The resulting detection volume of less than 650 zl represents 60,000x smaller volume than previous NMR microscopy and demonstrates the feasibility of pushing magnetic resonance imaging into the nanoscale regime.Comment: 24 pages, 5 figure

The Reinforcing Therapist Performance (RTP) experiment: Study protocol for a cluster randomized trial

<p>Abstract</p> <p>Background</p> <p>Rewarding provider performance has been recommended by the Institute of Medicine as an approach to improve the quality of treatment, yet little empirical research currently exists that has examined the effectiveness and cost-effectiveness of such approaches. The aim of this study is to test the effectiveness and cost-effectiveness of providing monetary incentives directly to therapists as a method to improve substance abuse treatment service delivery and subsequent client treatment outcomes.</p> <p>Design</p> <p>Using a cluster randomized design, substance abuse treatment therapists from across 29 sites were assigned by site to either an implementation as usual (IAU) or pay-for-performance (P4P) condition.</p> <p>Participants</p> <p>Substance abuse treatment therapists participating in a large dissemination and implementation initiative funded by the Center for Substance Abuse Treatment.</p> <p>Intervention</p> <p>Therapists in both conditions received comprehensive training and ongoing monitoring, coaching, and feedback. However, those in the P4P condition also were given the opportunity to earn monetary incentives for achieving two sets of measurable behaviors related to quality implementation of the treatment.</p> <p>Outcomes</p> <p>Effectiveness outcomes will focus on the impact of the monetary incentives to increase the proportion of adolescents who receive a targeted threshold level of treatment, months that therapists demonstrate monthly competency, and adolescents who are in recovery following treatment. Similarly, cost-effectiveness outcomes will focus on cost per adolescent receiving targeted threshold level of treatment, cost per month of demonstrated competence, and cost per adolescent in recovery.</p> <p>Trial Registration</p> <p>Trial Registration Number: NCT01016704</p