447 research outputs found

    Cardiorespiratory Progression Over 5 Years and Role of Corticosteroids in Duchenne Muscular Dystrophy: A Single-Site Retrospective Longitudinal Study

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    Background: Duchenne muscular dystrophy (DMD) boys treated with corticosteroids (CS) have prolonged survival and respiratory function when compared to CS-naïve. /\ud Research question: The differential impact of frequently used corticosteroids and their regimens on long-term (>5 years) cardiorespiratory progression in DMD children is unknown. / Study Design and Methods: Retrospective longitudinal study including DMD children followed at Dubowitz Neuromuscular Centre (Great Ormond Street Hospital London), May 2000-June 2017. Patients enrolled in any interventional clinical trials were excluded. We collected patients’ anthropometrics, respiratory (forced vital capacity, FVC% predicted and absolute FVC, non-invasive ventilation requirement, NIV) and cardiac (left ventricular shortening function, LVFS%) function. CS-naïve patients had never received CS. CS-treated took either deflazacort or prednisolone, daily or intermittently (10 days on/10 days off) for >1 month. Average longitudinal models were fitted for yearly respiratory (FVC%P) and cardiac (LVFS%) progression. A time-to-event analysis to FVC%P<50%, NIV start and cardiomyopathy (LVFS<28%) was performed in CS-treated (daily and intermittent) vs CS-naïve patients. / Results: There were 270 patients, mean age at baseline 6.2 (±2.3) years. Median follow-up 5.6 (± 3.5) years. At baseline, 263 were ambulant. Sixty-six were CS-daily, 182 CS-intermittent >60% treatment, 22 CS-naïve. Yearly FVC%P declined similarly from 9 years (5.9% and 6.9%/year, p=0.27) in CS-daily and CS-intermittent. CS-daily declined from a higher FVC%P than CS-intermittent (p2 years later than CS-treated. LVFS% declined by 0.53%/year in CS-treated irrespective of CS regimen, significantly slower (p<0.01) than CS-naïve progressing by 1.17%/year. Age at cardiomyopathy was 16.6 in CS-treated (p<0.05) irrespective of regimen and 13.9 years in CS-naïve. / Interpretation: CS irrespective of their regimen significantly improved respiratory function and delayed NIV requirement and cardiomyopathy

    Toothache and associated factors in Brazilian adults: a cross-sectional population-based study

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    Extent: 8p.Background: Toothache is a dental public health problem and one of the predictors of dental attendance and it is strongly associated with the life quality of individuals. In spite of this, there are few population-based epidemiological studies on this theme. Objective: To estimate the prevalence of toothache and associated factors in adults of Lages, Southern Brazil. Methods: A cross-sectional population-based study was carried out in a sample of 2,022 adults aged 20 to 59 years living in the urban area of a medium sized city in Southern Brazil. A questionnaire including socioeconomic, demographic, smoking, alcohol, and use of dental service variables was applied at adults household. Toothache occurred six months previous of the interview was considered the outcome. Poisson regression analyses were performed following a theoretical hierarchical framework. All analysis was adjusted by the sample design effect. Results: The response rate was 98.6%. The prevalence of toothache was 18.0% (95% CI 16.0; 20.1). The following variables were associated with toothache after adjustment: female (PR = 1.3 95% CI 1.3; 2.0), black skin colour vs. whites (PR = 1.5 95% CI 1.1, 1.9), low per capita income (PR = 1.7 95% CI 1.2, 2.3), smokers (PR = 1.5 95% CI 1.2, 1.9) and those who reported alcohol problems (PR = 1.4 95% CI 1.1; 1.9). To be 40 years of age (PR = 0.5 95% CI 0.4, 0.7) and use dental service in the last year (RR = 0.5 95% CI 0.4, 0.6) were protective factors for toothache. Conclusion: The prevalence of toothache in adults of Lages can be considered a major problem of dental public health.Mirian Kuhnen, Marco A Peres, Anelise V Masiero and Karen G Pere

    Preparation and Characterization of Cationic PLA-PEG Nanoparticles for Delivery of Plasmid DNA

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    The purpose of the present work was to formulate and evaluate cationic poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) nanoparticles as novel non-viral gene delivery nano-device. Cationic PLA-PEG nanoparticles were prepared by nanoprecipitation method. The gene loaded nanoparticles were obtained by incubating the report gene pEGFP with cationic PLA-PEG nanoparticles. The physicochemical properties (e.g., morphology, particle size, surface charge, DNA binding efficiency) and biological properties (e.g., integrity of the released DNA, protection from nuclease degradation, plasma stability, in vitro cytotoxicity, and in vitro transfection ability in Hela cells) of the gene loaded PLA-PEG nanoparticles were evaluated, respectively. The obtained cationic PLA-PEG nanoparticles and gene loaded nanoparticles were both spherical in shape with average particle size of 89.7 and 128.9 nm, polydispersity index of 0.185 and 0.161, zeta potentials of +28.9 and +16.8 mV, respectively. The obtained cationic PLA-PEG nanoparticles with high binding efficiency (>95%) could protect the loaded DNA from the degradation by nuclease and plasma. The nanoparticles displayed sustained-release properties in vitro and the released DNA maintained its structural and functional integrity. It also showed lower cytotoxicity than Lipofectamine 2000 and could successfully transfect gene into Hela cells even in presence of serum. It could be concluded that the established gene loaded cationic PLA-PEG nanoparticles with excellent properties were promising non-viral nano-device, which had potential to make cancer gene therapy achievable

    What traits are carried on mobile genetic elements, and why?

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    Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes

    AFCo1, a meningococcal B-derived cochleate adjuvant, strongly enhances antibody and T-cell immunity against Plasmodium falciparum merozoite surface protein 4 and 5

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    <p>Abstract</p> <p>Background</p> <p>Whilst a large number of malaria antigens are being tested as candidate malaria vaccines, a major barrier to the development of an effective vaccine is the lack of a suitable human adjuvant capable of inducing a strong and long lasting immune response. In this study, the ability of AFCo1, a potent T and B cell adjuvant based on cochleate structures derived from meningococcal B outer membrane proteoliposomes (MBOMP), to boost the immune response against two <it>Plasmodium falciparum </it>antigens, merozoite surface protein 4 (MSP4) and 5 (MSP5), was evaluated.</p> <p>Methods</p> <p>Complete Freund's adjuvant (CFA), which is able to confer protection against malaria in animal MSP4/5 vaccine challenge models, was used as positive control adjuvant. MSP4 and 5-specific IgG, delayed-type hypersensitivity (DTH), T-cell proliferation, and cytokine production were evaluated in parallel in mice immunized three times intramuscularly with MSP4 or MSP5 incorporated into AFCo1, synthetic cochleate structures, CFA or phosphate buffered saline.</p> <p>Results</p> <p>AFCo1 significantly enhanced the IgG and T-cell response against MSP4 and MSP5, with a potency equivalent to CFA, with the response being characterized by both IgG1 and IgG2a isotypes, increased interferon gamma production and a strong DTH response, consistent with the ability of AFCo1 to induce Th1-like immune responses.</p> <p>Conclusion</p> <p>Given the proven safety of MBOMP, which is already in use in a licensed human vaccine, AFCo1 could assist the development of human malaria vaccines that require a potent and safe adjuvant.</p

    Influenza Virus in Human Exhaled Breath: An Observational Study

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    Background: Recent studies suggest that humans exhale fine particles during tidal breathing but little is known of their composition, particularly during infection. Methodology/Principal Findings: We conducted a study of influenza infected patients to characterize influenza virus and particle concentrations in their exhaled breath. Patients presenting with influenza-like-illness, confirmed influenza A or B virus by rapid test, and onset within 3 days were recruited at three clinics in Hong Kong, China. We collected exhaled breath from each subject onto Teflon filters and measured exhaled particle concentrations using an optical particle counter. Filters were analyzed for influenza A and B viruses by quantitative polymerase chain reaction (qPCR). Twelve out of thirteen rapid test positive patients provided exhaled breath filter samples (7 subjects infected with influenza B virus and 5 subjects infected with influenza A virus). We detected influenza virus RNA in the exhaled breath of 4 (33%) subjects-three (60%) of the five patients infected with influenza A virus and one (14%) of the seven infected with influenza B virus. Exhaled influenza virus RNA generation rates ranged from <3.2 to 20 influenza virus RNA particles per minute. Over 87% of particles exhaled were under 1 μm in diameter. Conclusions: These findings regarding influenza virus RNA suggest that influenza virus may be contained in fine particles generated during tidal breathing, and add to the body of literature suggesting that fine particle aerosols may play a role in influenza transmission. © 2008 Fabian et al.published_or_final_versio

    Casting for a sovereign role:Socialising an aspirant state in the Scottish independence referendum

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    This article examines international reactions to Scotland’s 2014 bid for independence as an instance of socialisation of an aspirant state, what we term ‘pre-socialisation’. Building on and contributing to research on state socialisation and role theory, this study proposes a nexus between roles and sovereignty. This nexus has three components: sovereignty itself is a role casted for by an actor; the sovereign role is entangled with the substantive foreign policy roles the actor might play; and the sovereign role implicates the substantive foreign policy roles of other actors. The Scottish debate on independence provides an effective laboratory to develop and explore these theoretical dimensions of pre-socialisation, revealing the contested value and meaning of sovereignty, the possible roles that an independent Scotland could play, and the projected implications for the role of the UK and other international actors. Our analysis of the Scottish case can provide insights for other cases of pre-socialisation and is more empirically significant following the UK’s 2016 referendum to leave the European Union.PostprintPeer reviewe

    Serologically defined variations in malaria endemicity in Pará state, Brazil

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    BACKGROUND: Measurement of malaria endemicity is typically based on vector or parasite measures. A complementary approach is the detection of parasite specific IgG antibodies. We determined the antibody levels and seroconversion rates to both P. vivax and P. falciparum merozoite antigens in individuals living in areas of varying P. vivax endemicity in Pará state, Brazilian Amazon region. METHODOLOGY/PRINCIPAL FINDINGS: The prevalence of antibodies to recombinant antigens from P. vivax and P. falciparum was determined in 1,330 individuals. Cross sectional surveys were conducted in the north of Brazil in Anajás, Belém, Goianésia do Pará, Jacareacanga, Itaituba, Trairão, all in the Pará state, and Sucuriju, a free-malaria site in the neighboring state Amapá. Seroprevalence to any P. vivax antigens (MSP1 or AMA-1) was 52.5%, whereas 24.7% of the individuals were seropositive to any P. falciparum antigens (MSP1 or AMA-1). For P. vivax antigens, the seroconversion rates (SCR) ranged from 0.005 (Sucuriju) to 0.201 (Goianésia do Pará), and are strongly correlated to the corresponding Annual Parasite Index (API). We detected two sites with distinct characteristics: Goianésia do Pará where seroprevalence curve does not change with age, and Sucuriju where seroprevalence curve is better described by a model with two SCRs compatible with a decrease in force of infection occurred 14 years ago (from 0.069 to 0.005). For P. falciparum antigens, current SCR estimates varied from 0.002 (Belém) to 0.018 (Goianésia do Pará). We also detected a putative decrease in disease transmission occurred ∼29 years ago in Anajás, Goianésia do Pará, Itaituba, Jacareacanga, and Trairão. CONCLUSIONS: We observed heterogeneity of serological indices across study sites with different endemicity levels and temporal changes in the force of infection in some of the sites. Our study provides further evidence that serology can be used to measure and monitor transmission of both major species of malaria parasite

    An Arthroscopic Device to Assess Articular Cartilage Defects and Treatment with a Hydrogel

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    The hydraulic resistance R across osteochondral tissue, especially articular cartilage, decreases with degeneration and erosion. Clinically useful measures to quantify and diagnose the extent of cartilage degeneration and efficacy of repair strategies, especially with regard to pressure maintenance, are still developing. The hypothesis of this study was that hydraulic resistance provides a quantitative measure of osteochondral tissue that could be used to evaluate the state of cartilage damage and repair. The aims were to (1) develop a device to measure R in an arthroscopic setting, (2) determine whether the device could detect differences in R for cartilage, an osteochondral defect, and cartilage treated using a hydrogel ex vivo, and (3) determine how quickly such differences could be discerned. The apparent hydraulic resistance of defect samples was ~35% less than intact cartilage controls, while the resistance of hydrogel-filled groups was not statistically different than controls, suggesting some restoration of fluid pressurization in the defect region by the hydrogel. Differences in hydraulic resistance between control and defect groups were apparent after 4 s. The results indicate that the measurement of R is feasible for rapid and quantitative functional assessment of the extent of osteochondral defects and repair. The arthroscopic compatibility of the device demonstrates the potential for this measurement to be made in a clinical setting
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