A randomised control trial of the effectiveness of personalised letters sent subsequent to school dental inspections in increasing registration in unregistered children

<p>Abstract</p> <p>Background</p> <p>Recent studies have cast doubt on the effectiveness and efficiency of school based dental screening programmes in improving dental attendance or improving dental health. In 2002 the National Dental Inspection Programme was introduced in Scotland which categorises children by their dental health and informs parents of the findings via a personalised letter home and encourages dental registration. In addition, epidemiological data for local and national planning purposes is collected. This replaced an earlier school screening system in Lothian where a generic letter urging registration was sent to children who were identified as not being registered with a dentist. The objective of this study is to compare dental registrations rates among unregistered children in these two school inspection systems with a system where letters were sent home but no dental inspection was carried out.</p> <p>Methods</p> <p>The study was designed as a single blinded, cluster randomised, controlled trial involving 12,765 12–13-year-old children attending all 65 state Secondary schools in Lothian and Fife during the academic year 2003/4.</p> <p>After stratifying for school size and range of social deprivation, schools were randomly allocated to one of four groups:</p> <p>1. 'Traditional' inspection, letter to unregistered children only,</p> <p>2. Letter sent home to unregistered children only, no inspection,</p> <p>3. National Dental Inspection Programme, letter to all children,</p> <p>4. Control group in which the children were neither inspected nor sent a letter.</p> <p>Dental Registration status was compared at baseline and 3 months post inspection.</p> <p>Results</p> <p>The registration levels in both the 'Traditional' screening and the NDIP inspection groups rose 3 months post inspection (14% and 15.8% respectively) but were not significantly different from one another or the control group which rose by 15.8% (p > 0.05). The group who were sent a letter home but were not inspected also has a rise in registration levels of 18.1% which was not significantly different from either of the groups who were inspected or the control group (p > 0.05). The only significant predictors of registration were previous registration (p < 0.05) and within those who previously registered, the length of time since last registration (P < 0.001).</p> <p>Conclusion</p> <p>Neither of the two dental inspection methods nor a letter home to unregistered children resulted in a significant rise in registration rates in 12–13-year-olds compared to a control group of children who received no intervention.</p

Designed Azolopyridinium Salts Block Protective Antigen Pores In Vitro and Protect Cells from Anthrax Toxin

Background:Several intracellular acting bacterial protein toxins of the AB-type, which are known to enter cells by endocytosis, are shown to produce channels. This holds true for protective antigen (PA), the binding component of the tripartite anthrax-toxin of Bacillus anthracis. Evidence has been presented that translocation of the enzymatic components of anthrax-toxin across the endosomal membrane of target cells and channel formation by the heptameric/octameric PA63 binding/translocation component are related phenomena. Chloroquine and some 4-aminoquinolones, known as potent drugs against Plasmodium falciparium infection of humans, block efficiently the PA63-channel in a dose dependent way.Methodology/Principal Findings:Here we demonstrate that related positively charged heterocyclic azolopyridinium salts block the PA63-channel in the μM range, when both, inhibitor and PA63 are added to the same side of the membrane, the cis-side, which corresponds to the lumen of acidified endosomal vesicles of target cells. Noise-analysis allowed the study of the kinetics of the plug formation by the heterocycles. In vivo experiments using J774A.1 macrophages demonstrated that the inhibitors of PA63-channel function also efficiently block intoxication of the cells by the combination lethal factor and PA63 in the same concentration range as they block the channels in vitro.Conclusions/Significance:These results strongly argue in favor of a transport of lethal factor through the PA63-channel and suggest that the heterocycles used in this study could represent attractive candidates for development of novel therapeutic strategies against anthrax. © 2013 Beitzinger et al

Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

Abstract Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline

Quantifying the third sector in Portugal : an overview and evolution from 1997 to 2007

I am grateful to the Portuguese Ministry of Labor and Social Solidarity, Statistics Department, for access to the data used in this study (Quadros de Pessoal). I would also like to express my gratitude to Miguel Reis Portela and Nelson Areal for their assistance in dealing with the database and STATA. I am also indebted to two anonymous reviewers for their useful comments on an earlier version of this paper.This paper presents a global overview of the third sector in Portugal drawing on data from a linked employer-employee database – “Quadros de Pessoal”, which is based on a compulsory annual inquiry to organizations, making it a better source of information than those based on sample surveys and estimates. This study advances on previous overviews by providing more updated numbers for organization size, age, gross revenue and employment levels, as well as their distribution across the ICNPO third sector activity classification. The evolution of these variables from the period 1997-2007 is also analyzed. The Portuguese third sector has been fast growing, with revenues amounting to 5.64% of Portugal’s GDP and employment representing 4% of the country’s employment in 2007. It is mainly composed of very small organizations, with diminutive revenues. Perhaps its most striking features are the uneven distribution of employment and revenue and the strong concentration on Social services

A Quantitative Analytical Method to Test for Salt Effects on Giant Unilamellar Vesicles

Today, free-standing membranes, i.e. liposomes and vesicles, are used in a multitude of applications, e.g. as drug delivery devices and artificial cell models. Because current laboratory techniques do not allow handling of large sample sizes, systematic and quantitative studies on the impact of different effectors, e.g. electrolytes, are limited. In this work, we evaluated the Hofmeister effects of ten alkali metal halides on giant unilamellar vesicles made of palmitoyloleoylphosphatidylcholine for a large sample size by combining the highly parallel water-in-oil emulsion transfer vesicle preparation method with automatic haemocytometry. We found that this new quantitative screening method is highly reliable and consistent with previously reported results. Thus, this method may provide a significant methodological advance in analysis of effects on free-standing model membranes

Disease Trajectories in the Revised Hammersmith Scale in a Cohort of Untreated Patients with Spinal Muscular Atrophy types 2 and 3

Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder characterised by progressive motor function decline. Motor function is assessed using several functional outcome measures including the Revised Hammersmith Scale (RHS). Objective: In this study, we present longitudinal trajectories for the RHS in an international cohort of 149 untreated paediatric SMA 2 and 3 patients (across 531 assessments collected between March 2015 and July 2019). Methods: We contextualise these trajectories using both the Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM). At baseline, this cohort included 50% females and 15% of patients had undergone spinal fusion surgery. Patient trajectories were modelled using a natural cubic spline with age, sex, and random effects for each patient. Results: RHS and HFMSE scores show similar trends over time in this cohort not receiving disease modifying therapies. The results confirm the strong correlation between the RHS and RULM previously observed in SMA types 2 and 3a. Scoliosis surgery is associated with a reduction of 3 points in the RHS, 4.5 points in the HFMSE for the SMA 2 population, and a reduction of 11.8 points in the RHS, and 13.4 points in the HFMSE for the SMA 3a populations. When comparing the RHS and RULM, there is a lower correlation in the type 3a\u27s than the type 2 patients. In the SMA 2 population, there is no significant difference between the sexes in either the RHS or HFMSE trajectories. There is no significant difference in the RULM trajectory in the SMA 2 or 3a participants by sex. Conclusions: This study demonstrates that the RHS could be used in conjunction with other functional measures such as the RULM to holistically detect SMA disease progression. This will assist with fully understanding changes that occur with treatments, further defining trajectories and therapy outcomes

Evaluation of the antibacterial and anticancer activities of some South African medicinal plants

<p>Abstract</p> <p>Background</p> <p>Several herbs are traditionally used in the treatment of a variety of ailments particularly in the rural areas of South Africa where herbal medicine is mainly the source of health care system. Many of these herbs have not been assessed for safety or toxicity to tissue or organs of the mammalian recipients.</p> <p>Methods</p> <p>This study evaluated the cytotoxicity of some medicinal plants used, inter alia, in the treatment of diarrhoea, and stomach disorders. Six selected medicinal plants were assessed for their antibacterial activities against ampicillin-resistant and kanamycin-resistant strains of <it>Escherichia coli </it>by the broth micro-dilution methods. The cytotoxicities of methanol extracts and fractions of the six selected plants were determined using a modified tetrazolium-based colorimetric assay (3-(4, 5-dimethylthiazol)-2, 5-diphenyl tetrazolium bromide (MTT) assay).</p> <p>Results</p> <p>The average minimum inhibitory concentration (MIC) values of the plants extracts ranged from 0.027 mg/mℓ to 2.5 mg/mℓ after 24 h of incubation. <it>Eucomis autumnalis </it>and <it>Cyathula uncinulata </it>had the most significant biological activity with the least MIC values. The in vitro cytotoxicity assay on human hepatocarcinoma cell line (Huh-7) revealed that the methanol extract of <it>E. autumnalis </it>had the strongest cytotoxicity with IC₅₀of 7.8 μg/mℓ. Ethyl acetate and butanol fractions of <it>C. uncinulata, Hypoxis latifolia, E. autumnalis </it>and <it>Lantana camara </it>had lower cytotoxic effects on the cancer cell lines tested with IC₅₀values ranging from 24.8 to 44.1 μg/mℓ; while all the fractions of <it>Aloe arborescens </it>and <it>A. striatula </it>had insignificant or no cytotoxic effects after 72 h of treatment.</p> <p>Conclusions</p> <p>Our results indicate that the methanol fraction of <it>E. autumnalis </it>had a profound cytotoxic effect even though it possessed very significant antibacterial activity. This puts a query on its safety and hence a call for caution in its usage, thus a product being natural is not tantamount to being entirely safe. However, the antibacterial activities and non-cytotoxic effects of <it>A. arborescens </it>and <it>A. striatula </it>validates their continuous usage in ethnomedicine.</p

Human IgG/FcγR Interactions Are Modulated by Streptococcal IgG Glycan Hydrolysis

BACKGROUND: The human pathogen Streptococcus pyogenes produces an endoglycosidase, EndoS that hydrolyzes the chitobiose core of the asparagine-linked glycan on the heavy chain of human IgG. IgG-binding to Fc gamma receptors (FcgammaR) on leukocytes triggers effector functions including phagocytosis, oxidative burst and the release of inflammatory mediators. The interactions between FcgammaR and the Fc domain of IgG depend on the IgG glycosylation state. METHODOLOGY/PRINCIPAL FINDINGS: Here we show for the first time that EndoS hydrolyzes the heavy chain glycan of all four human IgG subclasses (IgG1-4), in purified form and in a plasma environment. An inactive form of EndoS, obtained by site-directed mutagenesis, binds IgG with high affinity, in contrast to wild type EndoS that only transiently interacts with IgG, as shown by Slot-blotting and surface plasmon resonance technology. Furthermore, EndoS hydrolysis of the IgG glycan influences the binding of IgG to immobilized soluble FcgammaR and to an erythroleukemic cell line, K562, expressing FcgammaRIIa. Incubation of whole blood with EndoS results in a dramatic decrease of IgG binding to activated monocytes as analyzed by flow cytometry. Moreover, the IgG bound to K562 cells dissociates when cells are treated with EndoS. Likewise, IgG bound to immobilized FcgammaRIIa and subsequently treated with EndoS, dissociates from the receptor as analyzed by surface plasmon resonance and Western blot. CONCLUSIONS/SIGNIFICANCE: We provide novel information about bacterial enzymatic modulation of the IgG/FcgammaR interaction that emphasizes the importance of glycosylation for antibody effector functions. Moreover, EndoS could be used as a biochemical tool for specific IgG N-glycan hydrolysis and IgG purification/detection, or as a potential immunosuppressing agent for treatment of antibody-mediated pathological processes