Enhanced Trabeculectomy: The Moorfields Safer Surgery System

Trabeculectomy with antifibrotic treatment is still the most popular incisional procedure for glaucoma filtration surgery (GFS) worldwide. The advent of antifibrotic agents reduced failure due to scarring but resulted in increased complications. Advances in trabeculectomy surgery have been driven by the need to minimise the risk of: (1) complications and (2) surgical failure. This chapter covers preoperative, intraoperative, and postoperative strategies, which improve the outcome of GFS. Strategies to reduce the risk of complications centre on the prevention of postoperative hypotony by minimising the risk of overdrainage, postoperative wound leaks, and poor bleb morphology. Surgical techniques to reduce the risk of postoperative fibrosis by the use of antifibrotic agents (including mitomycin C) are discussed in detail. These techniques are based on a combination of considerable clinical experience, observation, and laboratory research. The need to address pre-, intra-, and postoperative issues in each individual patient is emphasised. These changes are embodied in the system we call the "Moorfields Safer Surgery System." The use of these strategies has considerably reduced the incidence of major complications, including hypotony, cystic blebs, and endophthalmitis in practices around the world. Most of these techniques are simple, require minimal equipment, and can be easily mastered. They are associated with an improvement in overall outcome and it is hoped that this chapter will help the reader benefit from these advances

Late spontaneous rupture of the extensor pollicis longus tendon after corticosteroid injection for flexor tenosynovitis

INTRODUCTION: Spontaneous rupture of the extensor pollicis longus (EPL) tendon has been reported after trauma, rheumatoid arthritis and sports. Rupture may also occur as a consequence of the use of anabolic steroids for recreational purposes, or systemic steroids for the treatment of a variety of medical conditions. CASE REPORT: We present a case report of a woman affected with a spontaneous EPL tendon rupture resulted 14 months after a corticosteroid injection for flexor tenosynovitis, "trigger finger," of the thumb. The edges of the tendon were debrided and sutured using figure of eight stitch and a running locked stitch. In addition multiple specimens were sent to Pathology. DISCUSSION: Duplay in 1876 described spontaneous rupture as a problem of mechanical and pressure phenomena. Another cause of EPL rupture is related to the development and persistence of inflammatory processes seen in patients with medical illnesses such as rheumatoid arthritis. There have been no reports in the literature to date of spontaneous EPL tendon rupture in the late period after steroid injection. Tendon ruptures in the hand usually occur one or two weeks after a corticosteroid injection, and the affected tendons are usually in neighbouring areas

Long-Term Outcomes of Trabeculectomy Augmented with Mitomycin C Undertaken within the First 2 Years of Life

To evaluate the long-term effectiveness and safety of mitomycin C (MMC)–augmented trabeculectomy undertaken within the first 2 years of life for the surgical management of glaucoma. DESIGN: Retrospective, consecutive, noncomparative case series. PARTICIPANTS: All children who underwent MMC-augmented trabeculectomy within 2 years of birth between May 2002 and November 2012. METHODS: The medical records of 40 consecutive eyes of 26 children who underwent surgery by a single surgeon were reviewed. Data collected during routine clinical care were analyzed. MAIN MEASURE OUTCOMES: Assessment of clinical outcomes included intraocular pressure (IOP), final visual acuity, bleb morphology, surgical complications (early and late), postoperative interventions, and further glaucoma surgery performed. Surgical success was defined as final IOP of 5 mmHg or more and of 21 mmHg or less, with anti-glaucoma medications (qualified success) and without (complete success), stable ocular dimensions and optic disc cupping, and no further glaucoma surgery (including needling) or loss of light perception. Surgical outcomes were evaluated using Kaplan-Meier life table analysis. RESULTS: Forty eyes of 26 children were studied over a mean follow-up period of 62.8 months. Most cases (80%) were of primary congenital glaucoma after failed goniotomy surgery. Cumulative probabilities of survival at 1, 5, and 7 years were 78%, 67%, and 60%, respectively. Of eyes regarded as successful, 96% (25/26 eyes) had controlled IOP without topical medication and 44% achieved visual acuity of 20/40 or better. In only 1 of the 40 eyes did a cystic avascular bleb develop, with all the other eyes being non-cystic in nature (diffuse and elevated or flat) at final follow-up. Sixty-four percent (9/14 eyes) of cases regarded as failures ultimately underwent glaucoma drainage device implantation. CONCLUSIONS: A contemporary pediatric trabeculectomy technique augmented with MMC is an effective procedure in the management of glaucoma within the first 2 years of life, as shown by the successful long-term outcomes and low incidence of sight-threatening complications. Trabeculectomy after failed goniotomy surgery or as a primary surgical intervention may offer a phakic infant with glaucoma an excellent opportunity to achieve long-term control of IOP without medications and may be associated with optimal visual outcomes

Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis.

Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers

CMB Telescopes and Optical Systems

The cosmic microwave background radiation (CMB) is now firmly established as a fundamental and essential probe of the geometry, constituents, and birth of the Universe. The CMB is a potent observable because it can be measured with precision and accuracy. Just as importantly, theoretical models of the Universe can predict the characteristics of the CMB to high accuracy, and those predictions can be directly compared to observations. There are multiple aspects associated with making a precise measurement. In this review, we focus on optical components for the instrumentation used to measure the CMB polarization and temperature anisotropy. We begin with an overview of general considerations for CMB observations and discuss common concepts used in the community. We next consider a variety of alternatives available for a designer of a CMB telescope. Our discussion is guided by the ground and balloon-based instruments that have been implemented over the years. In the same vein, we compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT). CMB interferometers are presented briefly. We conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and Planck, to demonstrate a remarkable evolution in design, sensitivity, resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1: Telescopes and Instrumentatio

Enhanced In Vitro Refolding of Fibroblast Growth Factor 15 with the Assistance of SUMO Fusion Partner

Fibroblast growth factor 15 (Fgf15) is the mouse orthologue of human FGF19. Fgf15 is highly expressed in the ileum and functions as an endocrine signal to regulate liver function, including bile acid synthesis, hepatocyte proliferation and insulin sensitivity. In order to fully understand the function of Fgf15, methods are needed to produce pure Fgf15 protein in the prokaryotic system. However, when expressed in Escherichia coli (E. coli), the recombinant Fgf15 protein was insoluble and found only in inclusion bodies. In the current study, we report a method to produce recombinant Fgf15 protein in E. coli through the use of small ubiquitin-related modifier (SUMO) fusion tag. Even though the SUMO has been shown to strongly improve protein solubility and expression levels, our studies suggest that the SUMO does not improve Fgf15 protein solubility. Instead, proper refolding of Fgf15 protein was achieved when Fgf15 was expressed as a partner protein of the fusion tag SUMO, followed by in vitro dialysis refolding. After refolding, the N-terminal SUMO tag was cleaved from the recombinant Fgf15 fusion protein by ScUlp1 (Ubiquitin-Like Protein-Specific Protease 1 from S. cerevisiae). With or without the SUMO tag, the refolded Fgf15 protein was biologically active, as revealed by its ability to reduce hepatic Cyp7a1 mRNA levels in mice. In addition, recombinant Fgf15 protein suppressed Cyp7a1 mRNA levels in a dose-dependent manner. In summary, we have developed a successful method to express functional Fgf15 protein in prokaryotic cells

An overview of the recent developments on fructooligosaccharide production and applications

Over the past years, many researchers have suggested that deficiencies in the diet can lead to disease states and that some diseases can be avoided through an adequate intake of relevant dietary components. Recently, a great interest in dietary modulation of the human gut has been registered. Prebiotics, such as fructooligosaccharides (FOS), play a key role in the improvement of gut microbiota balance and in individual health. FOS are generally used as components of functional foods, are generally regarded as safe (generally recognized as safe status—from the Food and Drug Administration, USA), and worth about 150€ per kilogram. Due to their nutrition- and health-relevant properties, such as moderate sweetness, low carcinogenicity, low calorimetric value, and low glycemic index, FOS have been increasingly used by the food industry. Conventionally, FOS are produced through a two-stage process that requires an enzyme production and purification step in order to proceed with the chemical reaction itself. Several studies have been conducted on the production of FOS, aiming its optimization toward the development of more efficient production processes and their potential as food ingredients. The improvement of FOS yield and productivity can be achieved by the use of different fermentative methods and different microbial sources of FOS producing enzymes and the optimization of nutritional and culture parameter; therefore, this review focuses on the latest progresses in FOS research such as its production, functional properties, and market data.Agencia de Inovacao (AdI)-Project BIOLIFE reference PRIME 03/347. Ana Dominguez acknowledges Fundacao para a Ciencia e a Tecnologia, Portugal, for her PhD grant reference SFRH/BD/23083/2005

Evaluating Nuclei Concentration in Amyloid Fibrillation Reactions Using Back-Calculation Approach

Background: In spite of our extensive knowledge of the more than 20 proteins associated with different amyloid diseases, we do not know how amyloid toxicity occurs or how to block its action. Recent contradictory reports suggest that the fibrils and/or the oligomer precursors cause toxicity. An estimate of their temporal concentration may broaden understanding of the amyloid aggregation process. Methodology/Principal Findings: Assuming that conversion of folded protein to fibril is initiated by a nucleation event, we back-calculate the distribution of nuclei concentration. The temporal in vitro concentration of nuclei for the model hormone, recombinant human insulin, is estimated to be in the picomolar range. This is a conservative estimate since the back-calculation method is likely to overestimate the nuclei concentration because it does not take into consideration fibril fragmentation, which would lower the amount of nuclei Conclusions: Because of their propensity to form aggregates (non-ordered) and fibrils (ordered), this very low concentration could explain the difficulty in isolating and blocking oligomers or nuclei toxicity and the long onset time for amyloid diseases

To be understood: Transitioning to adult life for people with Autism Spectrum Disorder

Introduction: The purpose of this study was to explore the viewpoints of parents of young people with Autism Spectrum Disorder (ASD) in relation to their child's transition to adulthood. Methods: Data were collected during four structured focus groups with 19 parents of young people with ASD with average to high intellectual capacities. Condensed meaning units were identified and checked during focus groups, and were subsequently linked to the International Classification of Functioning, Disability and Health (ICF). Results: Three major themes emerged: to be understood, to understand the world and to succeed. The ICF domains of activity and participation and environmental factors emerged as having the greatest potential to influence transition outcomes. Conclusions: Policies and services should focus on strengths to maximise participation in higher education, employment and independent living amongst young people with ASD. Interventions targeting environmental factors could be effective in improving participation in adult life. Person-centred and individualised approaches could further complement this approach supporting the transition to adulthood for people with ASD, ultimately improving outcomes in adulthood

Down-Regulation of Glucose-Regulated Protein (GRP) 78 Potentiates Cytotoxic Effect of Celecoxib in Human Urothelial Carcinoma Cells

Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor that has been reported to elicit anti-proliferative response in various tumors. In this study, we aim to investigate the antitumor effect of celecoxib on urothelial carcinoma (UC) cells and the role endoplasmic reticulum (ER) stress plays in celecoxib-induced cytotoxicity. The cytotoxic effects were measured by MTT assay and flow cytometry. The cell cycle progression and ER stress-associated molecules were examined by Western blot and flow cytometry. Moreover, the cytotoxic effects of celecoxib combined with glucose-regulated protein (GRP) 78 knockdown (siRNA), (−)-epigallocatechin gallate (EGCG) or MG132 were assessed. We demonstrated that celecoxib markedly reduces the cell viability and causes apoptosis in human UC cells through cell cycle G1 arrest. Celecoxib possessed the ability to activate ER stress-related chaperones (IRE-1α and GRP78), caspase-4, and CCAAT/enhancer binding protein homologous protein (CHOP), which were involved in UC cell apoptosis. Down-regulation of GRP78 by siRNA, co-treatment with EGCG (a GRP78 inhibitor) or with MG132 (a proteasome inhibitor) could enhance celecoxib-induced apoptosis. We concluded that celecoxib induces cell cycle G1 arrest, ER stress, and eventually apoptosis in human UC cells. The down-regulation of ER chaperone GRP78 by siRNA, EGCG, or proteosome inhibitor potentiated the cytotoxicity of celecoxib in UC cells. These findings provide a new treatment strategy against UC